| Trial | Phase | Enrollment | Study Type | Start Date | Status |
|---|
| Study on the Optimal Treatment for Poor Efficacy of Entecavir in Chronic Hepatitis B Patients [NCT03733652] | | 100 participants (Anticipated) | Interventional | 2018-11-15 | Not yet recruiting |
| A Phase III Randomized Trial Comparing Physician/Patient Choice of Either High Dose Interferon or Ipilimumab to MK-3475 (Pembrolizumab) in Patients With High Risk Resected Melanoma [NCT02506153] | Phase 3 | 1,345 participants (Actual) | Interventional | 2015-11-10 | Active, not recruiting |
| A Randomised, Parallel Group 2:1 Comparison of the Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) and Placebo in the Prevention of Multi-Organ Failure on Patients Surviving Open Surgery for a Ruptured Abdominal Aortic Aneurysm [NCT03119701] | Phase 2 | 40 participants (Actual) | Interventional | 2017-02-18 | Terminated(stopped due to IDMC recommendation. Unexpectedly high use of concomitant corticosteroid treatment.) |
| A Phase 2 Study of Telaprevir (VX-950) in Combination With Peginterferon Alfa-2a (Pegasys®), and Ribavirin (Copegus®) in Subjects With Genotype 1 Hepatitis C Who Have Not Achieved Sustained Viral Response With a Prior Course of Interferon Based Therapy [NCT00420784] | Phase 2 | 465 participants (Actual) | Interventional | 2007-02-28 | Completed |
| Effect of Aerobic Exercise on Side Effects of Disease Modifying Therapy With Subcutaneous Interferon-b1b in Patients With Multiple Sclerosis [NCT01122056] | | 128 participants (Anticipated) | Interventional | 2010-05-31 | Completed |
| An Open Label, Nonrandomized, Single-center, Phase I Trial of Pretreated Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia Patients in Chronic Phase (CML-CP) With Nilotinib in Combination With Low Dose Interferon-alpha (IFN) - NICOLI Study - [NCT01220648] | Phase 1 | 4 participants (Actual) | Interventional | 2012-04-30 | Completed |
| A Randomized Study Comparing Imatinib And Imatinib/Pegylated Interferon Alpha-2B in Newly Diagnosed Non-high Risk Chronic Myeloid Leukemia Patients in Complete Hematological Remission After Imatinib Induction Therapy [NCT01227356] | Phase 2 | 112 participants (Actual) | Interventional | 2004-09-30 | Completed |
| Postmarketing Surveillance Study on the Extent to Which Patient Compliance is Influenced by Use of a Variable Titration Regimen at the Start of Treatment of Relapsing Multiple Sclerosis With Interferon Beta 1a (Rebif®) [NCT01142492] | | 403 participants (Actual) | Observational | 2005-01-31 | Completed |
| A Phase 2 Study of VX-950 in Combination With Peginterferon Alfa-2a (Pegasys®), With Ribavirin (Copegus®) in Subjects With Genotype 1 Hepatitis C Who Have Not Received Prior Treatment [NCT00336479] | Phase 2 | 263 participants (Actual) | Interventional | 2006-06-30 | Completed |
| HYMN: A Randomized Controlled Phase III Trial Comparing Hyperthermia Plus Mitomycin to a Second Course of Bacillus Calmette-Guerin or Standard Therapy in Patients With Recurrence of Non-Muscle Invasive Bladder Cancer Following Induction or Maintenance Bac [NCT01094964] | Phase 3 | 242 participants (Anticipated) | Interventional | 2009-10-31 | Recruiting |
| A Phase II, Randomized, Open-Label, Three-Arm Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Subcutaneous Interferon Beta-1a (Rebif®) in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis [NCT00050778] | Phase 2 | 334 participants (Actual) | Interventional | 2002-12-31 | Completed |
| Airway Intervention Registry (AIR) Extension: Recurrent Respiratory Papillomatosis [NCT03465280] | | 400 participants (Anticipated) | Observational [Patient Registry] | 2018-04-01 | Recruiting |
| A Randomized Phase II Study of Ipilimumab at 3 mg/kg or 10 mg/kg Alone or in Combination With High Dose Interferon-Alpha in Advanced Melanoma [NCT01708941] | Phase 2 | 88 participants (Actual) | Interventional | 2013-01-18 | Active, not recruiting |
| A Phase III Randomized Study of Adjuvant Ipilimumab Anti-CTLA4 Therapy Versus High-Dose Interferon a-2b for Resected High-Risk Melanoma [NCT01274338] | Phase 3 | 1,673 participants (Actual) | Interventional | 2011-05-25 | Active, not recruiting |
| "SWiss Atorvastatin and Interferon-Beta 1b Trial In Multiple Sclerosis - Follow up Study (SWABIMS Follow Up-study)" [NCT01111656] | Phase 2 | 28 participants (Actual) | Interventional | 2007-03-31 | Completed |
| Study of Pharmacokinetics and Pharmacodynamics of Alpha Interferon-2A of Blausiegel Trade and Industry the Compared the Product Roferon A, of Laboratory of Roche [NCT01228422] | | 24 participants (Anticipated) | Observational | 2009-03-31 | Completed |
| A Pilot Study to Evaluate the Safety and Efficacy of IFN-alfacon1 (INFERGEN) in the Treatment of Hospitalized Patients Presenting With Influenza-like Illnesses Due to the Pandemic 2009 Swine Origin Influenza A Virus (S-OIV) H1N1 and Other Circulating Infl [NCT01227798] | Phase 1/Phase 2 | 30 participants (Anticipated) | Interventional | 2010-11-30 | Not yet recruiting |
| A Clinical Controlled Study to Optimize the Therapeutic Pathway of Peginterferon Alfa-2b Treatment in Patients With Chronic Hepatitis B Based on IFNA2p.Ala120Thr /ISGs Gene Spectrum. [NCT03771677] | | 400 participants (Anticipated) | Interventional | 2018-12-01 | Recruiting |
| An Open Label Trial of Safety and Efficacy of Combination Therapy With Interferon-B-1a and Oral Doxycycline in Patients With Relapsing-remitting Multiple Sclerosis (RRMS) [NCT00246324] | Phase 4 | 16 participants (Actual) | Interventional | 2003-12-31 | Completed |
| Study of Immunological Activity After Personalized Immunomodulatory Therapy Regulating the Th17 Pathway in Patients With Membranous Nephropathy [NCT05941845] | Phase 2 | 5 participants (Anticipated) | Interventional | 2023-07-24 | Not yet recruiting |
| Pharmaco-immunological Study of Interferon-alpha and Metronomic Cyclophosphamide Association in Neuroendocrine Tumors [NCT02838342] | Phase 2 | 28 participants (Actual) | Interventional | 2015-05-19 | Completed |
| Nordic Randomized Phase III Trial of Two Different Durations of Adjuvant Therapy With Intermediate-dose Interferon Alfa-2b in Patients With High-risk Melanoma [NCT01259934] | Phase 3 | 855 participants (Actual) | Interventional | 1996-11-30 | Completed |
| Pilot Study of First Line Combination Treatment With Low Dose Pegylated Interferon and Entecavir in Treatment-naïve Patients With Chronic Hepatitis B. [NCT01589952] | Phase 1/Phase 2 | 20 participants (Anticipated) | Interventional | 2012-03-31 | Recruiting |
| Vumerity (Diroximel Fumarate) Prospective MS Pregnancy Exposure Registry [NCT05658497] | | 908 participants (Anticipated) | Observational [Patient Registry] | 2023-10-27 | Recruiting |
| Ribavirin Dose Optimization for the Treatment of Hepatitis C: A Pilot Study [NCT01289496] | Phase 2 | 13 participants (Actual) | Interventional | 2011-02-28 | Completed |
| A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Pegylated Interferon Lambda vs. Placebo in Subjects Infected With COVID-19 [NCT04343976] | Phase 2 | 14 participants (Actual) | Interventional | 2020-06-22 | Terminated(stopped due to Unable to meet enrollment goal, lack of funding.) |
| A RANDOMIZED PHASE 2/3 TRIAL OF SCH 54031 PEG12000 INTERFERON ALFA-2b (PEG INTRON, SCH 54031) VS. INTRON A (SCH 30500) IN SUBJECTS WITH NEWLY DIAGNOSED CML (PROTOCOL NOS. C/I98-026) [NCT03547154] | Phase 2/Phase 3 | 344 participants (Actual) | Interventional | 1998-10-22 | Terminated |
| Phase III Trial of High Dose Interferon Alfa 2-b Versus Cisplatin, Vinblastine, DTIC Plus IL-2 and Interferon in Patients With High Risk Melanoma [NCT00006237] | Phase 3 | 432 participants (Actual) | Interventional | 2000-08-31 | Completed |
| Allogeneic Hematopoietic Cell Transplantation With Pegylated Interferon Alfa-2a for Primary and Secondary Myelofibrosis (ATIOM) [NCT05535764] | Phase 1 | 18 participants (Anticipated) | Interventional | 2023-03-23 | Recruiting |
| The Benefit/Risk Profile of Pegylated Proline-Interferon Alpha-2b (AOP2014) Added to the Best Available Strategy Based on Phlebotomies in Low-risk Patients With Polycythemia Vera (PV). The Low-PV Randomized Trial [NCT03003325] | Phase 2 | 127 participants (Actual) | Interventional | 2017-02-02 | Completed |
| Phase 1 Study to Determine the Effects of Mesenchymal Stem Cells Secreting Interferon Beta in Patients With Advanced Ovarian Cancer [NCT02530047] | Phase 1 | 5 participants (Actual) | Interventional | 2016-05-16 | Completed |
| Role of Pegylated Interferon in Combination With Direct Acting Antivirals (DAAs) to Cure Hepatitis C As Soon As Possible (ASAP) - Hepatitis C [ASAP-C] [NCT03480932] | Phase 2/Phase 3 | 150 participants (Actual) | Interventional | 2018-02-02 | Completed |
| Single Arm Salvage Therapy With Pegylated Interferon Alfa-2a for Patients With High Risk Polycythemia Vera or High Risk Essential Thrombocythemia Who Are Either Hydroxyurea Resistant or Intolerant or Have Had Abdominal Vein Thrombosis [NCT01259817] | Phase 2 | 135 participants (Actual) | Interventional | 2011-09-30 | Completed |
| Real-World Betaseron® Outcomes Study (ROBUST): A Twelve-month, US Prospective, Observational, Open-label, Single-arm, Multi-center Outcomes Study of Interferon β-1b (Betaseron®) Given Every Other Day for Relapsing Forms of Multiple Sclerosis [NCT01158183] | | 226 participants (Actual) | Observational | 2007-07-31 | Completed |
| REsPonse to Interferon-Alpha in InterfeRon-β Neutralizing Antibody Positive Multiple Sclerosis Patients [NCT01171209] | Phase 2 | 10 participants (Actual) | Interventional | 2010-07-31 | Completed |
| Open-Label Rater-Blind Randomized Multi-Center Parallel-Arm Active- Comparator Study to Assess the Efficacy and Tolerability of Ofatumumab 20mg SC Monthly vs. First Line DMT - Physician's Choice in the Treatment of Newly Diagnosed RMS [NCT04788615] | Phase 3 | 186 participants (Anticipated) | Interventional | 2021-07-23 | Recruiting |
| Phase II Study Incorporating Pegylated Interferon In the Treatment For Children With High-Risk Melanoma [NCT00539591] | Phase 2 | 29 participants (Actual) | Interventional | 2008-05-09 | Active, not recruiting |
| Optical Coherence Tomography (OCT) in a Multicenter, Randomized,Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of PEGylated Interferon Beta-1a (BIIB017) in Subjects With Relapsing Multiple Sclerosis [NCT01337427] | Phase 3 | 0 participants (Actual) | Interventional | 2010-08-31 | Withdrawn(stopped due to The study was not feasible to conduct in the US and abroad.) |
| A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-3) [NCT04492475] | Phase 3 | 969 participants (Actual) | Interventional | 2020-08-05 | Completed |
| The Short-term Effect of Immunomodulatory Treatment With Interferon Beta-1b (Betaferon) on Fatigue and Depression in First-time Treated Patients With Relapsing-remitting Multiple Sclerosis. [NCT01354665] | | 567 participants (Actual) | Observational | 2010-05-31 | Completed |
| A Multicenter, Prospective, Non-interventional Study to Assess Adherence to Treatment for patIeNts With RMS Who Are Prescribed Subcutaneous (sc) Interferon Beta-1a (MAIN-MS) [NCT02921035] | | 594 participants (Actual) | Observational | 2016-06-30 | Completed |
| Comparison of Methotrexate Versus Interferon-alfa 2b on Efficacy, Safety and Quality of Life in Patients With Primary Cutaneous T-cell Lymphomas [NCT02323659] | Phase 4 | 100 participants (Anticipated) | Interventional | 2014-06-01 | Terminated(stopped due to Slow recruitment) |
| A Pilot Study to Determine the Feasibility of Conventional Induction Chemotherapy Followed by G-CSF Mobilized Donor Leukocyte Infusion (DLI) and IFN-α (IFN-DLI) for Relapsed Acute Leukemia After Allogeneic Stem Cell Transplantation. [NCT02331706] | Early Phase 1 | 16 participants (Actual) | Interventional | 2014-12-31 | Completed |
| Pegylated Interferon Alone or in Combination With Ezetimibe for Patients With Chronic Hepatitis D [NCT03105310] | Phase 2 | 20 participants (Anticipated) | Interventional | 2016-01-31 | Active, not recruiting |
| The Utility of Interferon-Gamma Release Assays in TB-HIV Co-infected Children [NCT00604617] | | 564 participants (Actual) | Observational | 2009-01-26 | Completed |
| Pilot Study to Assess the Efficacy and Safety of Boceprevir, in Combination With Peg-Interferon Alfa and Ribavirin, in Patients With HCV/HIV Co-infection Who Have Failed to a Previous Therapy With Peg-Interferon/Ribavirin [NCT01335529] | Phase 2 | 69 participants (Actual) | Interventional | 2011-05-31 | Completed |
| Combination Treatment of Nucleoside （Acid）Analogue (NAs) and Pegylated Interferon α-2b for NAs Treated, Hepatitis B Related, Compensatory Cirrhosis Patients With Low Level Hepatitis b Virus Surface Antigen (HBsAg) [NCT03969017] | Phase 2 | 84 participants (Anticipated) | Interventional | 2019-06-17 | Recruiting |
| Clinical Study of Pharmacokinetics and Pharmacodynamics of the Drug Interferon Beta-1a Produced By Laboratorio Quimico Farmaceutico Bergamo Compared To Interferon Beta-1a (Rebif - Merck Serono) In Healthy Subjects [NCT01074593] | Phase 1 | 20 participants (Actual) | Interventional | 2011-01-31 | Completed |
| Anti-Coronavirus Therapies to Prevent Progression of COVID-19, a Randomized Trial [NCT04324463] | Phase 3 | 6,667 participants (Actual) | Interventional | 2020-04-21 | Active, not recruiting |
| Role of Interferon-gamma 1-b (IFN-γ) on Cells of the Innate Immune System: Functional, Biochemical and Gene Expression Studies in Patients With Chronic Granulomatous Disease [NCT03548818] | | 9 participants (Actual) | Observational | 2018-05-16 | Completed |
| The Curative Effect and Security of Interferon Combined Resveratrol on HBeAg Positive Chronic Hepatitis B Patients - a Multi-center, Random, Control, Open Clinical Trial. [NCT03546530] | | 228 participants (Actual) | Interventional | 2016-06-01 | Completed |
| Randomized Trial to Evaluate the Safety and Efficacy of Outpatient Treatments to Reduce the Risk of Worsening in Individuals With COVID-19 With Risk Factors (COVERAGE France) [NCT04356495] | Phase 2/Phase 3 | 412 participants (Actual) | Interventional | 2020-07-29 | Completed |
| Boceprevir Treatment in Liver Pre-transplant HCV Patients [NCT02160080] | Phase 3 | 20 participants (Anticipated) | Interventional | 2014-01-31 | Recruiting |
| Safety and Efficacy of γIFN Treatment in Friedreich Ataxia [NCT03888664] | Phase 2 | 12 participants (Actual) | Interventional | 2016-06-26 | Completed |
| A Randomized, Multicenter, Unblinded, Phase III Study Assessing the Loss of HbsAg at W96 After a 48-week Pegylated Interferon Alpha 2a in Patients With Chronic Hepatitis B (HbeAg Negative) Under Treatment and Responders (Undetectable Viral Load) to a Nucl [NCT01172392] | Phase 3 | 185 participants (Actual) | Interventional | 2011-01-31 | Active, not recruiting |
| "Phase II Multicenter Study Evaluating the Efficacy and the Safety of a Combination of Nilotinib Plus Pegylated Interferon Alpha 2a for de Novo Chronic Phase Chronic Myelogenous Leukemia Patients" [NCT01294618] | Phase 2 | 60 participants (Actual) | Interventional | 2011-03-31 | Completed |
| A Phase II Clinical Trial to Evaluate the Efficacy of BAY 43-9006 With or Without Low Dose Interferon in Metastatic Renal Cell Carcinoma [NCT00126594] | Phase 2 | 80 participants (Actual) | Interventional | 2005-06-30 | Completed |
| Post-Authorization Observational Study to Evaluate Cognition and Fatigue in RRMS Patients Treated With Rebif [NCT01075880] | | 300 participants (Actual) | Observational | 2009-05-31 | Completed |
| A Multicentre, Single Arm, Open-Label, Phase IIIB Study to Evaluate the Safety and Antigenicity of Rebif® (Interferon-beta-1a) in Subjects With Relapsing Forms of Multiple Sclerosis [NCT00110396] | Phase 3 | 260 participants (Actual) | Interventional | 2005-01-31 | Completed |
| A Phase 3, Randomized Study Of SU011248 Versus Interferon-Alfa As First-Line Systemic Therapy For Patients With Metastatic Renal Cell Carcinoma [NCT00083889] | Phase 3 | 750 participants (Actual) | Interventional | 2004-08-31 | Completed |
| Phase IV, Multicenter, Open Label, Randomized Study of Rebif® 44 mcg Administered Three Times Per Week by Subcutaneous Injection Compared With Copaxone® 20 mg Administered Daily by Subcutaneous Injection in the Treatment of Relapsing Remitting Multiple Sc [NCT00078338] | Phase 4 | 764 participants (Actual) | Interventional | 2004-02-16 | Completed |
| Pilot Study: Single Arm, Multi-site, Open-label Study to Assess the Effectiveness of Peg-IFN-a2b in Decreasing the Levels of Cell-associated Integrated Viral DNA in HIV Chronic Infection [NCT01935089] | Phase 2 | 20 participants (Actual) | Interventional | 2013-08-07 | Completed |
| Phase I Trial of Intratumoral Injection of Vesicular Stomatitis Virus Expressing Human Interferon Beta in Patients With Sorafenib Refractory/Intolerant Hepatocellular Carcinoma, Advanced Solid Tumors With Liver Predominant Locally Advanced/Metastatic Dise [NCT01628640] | Phase 1 | 17 participants (Actual) | Interventional | 2012-08-03 | Active, not recruiting |
| A Phase 3, Three-Arm, Randomized, Open-Label Study Of Interferon Alfa Alone, CCI-779 Alone, And The Combination Of Interferon Alfa And CCI-779 In First-Line Poor-Prognosis Subjects With Advanced Renal Cell Carcinoma. [NCT00065468] | Phase 3 | 626 participants (Actual) | Interventional | 2003-07-31 | Completed |
| PROTECT - Pegylated Interferon Alfa-2b and Ribavirin After Orthotopic Liver Transplantation: Efficacy and Safety in Hepatitis C Recurrence Therapy [NCT00378599] | Phase 3 | 125 participants (Actual) | Interventional | 2006-05-31 | Completed |
| Sequential High-Dose Melphalan and Busulfan/Cyclophosphamide Followed by Peripheral Blood Progenitor Cell Rescue, Interferon/Thalidomide and Pamidronate for Patients With Multiple Myeloma [NCT00004088] | Phase 2 | 77 participants (Actual) | Interventional | 1999-04-13 | Completed |
| Phase II Trial of Atragen and Interferon Alfa-2b in Patients With Advanced Renal Cell Carcinoma [NCT00003656] | Phase 2 | 26 participants (Actual) | Interventional | 1999-01-31 | Completed |
| Post Marketing Surveillance Study to Evaluate the Tolerability of Rebif® New Formulation in Patients With Relapsing Multiple Sclerosis in an Australian Clinical Setting [NCT01101776] | | 49 participants (Actual) | Observational | 2010-01-31 | Completed |
| A Phase 3 Safety and Efficacy Study of Boceprevir in Subjects With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin [NCT00708500] | Phase 3 | 404 participants (Actual) | Interventional | 2008-08-31 | Completed |
| Comparative Pharmacokinetic Profile of Interferon Beta-1a (Bioferon®) Administered as Single i.v. Doses in HSA-free Formulation and HSA+ Solution and as Multiple s.c. Doses in Healthy Subjects [NCT02517788] | Phase 1 | 24 participants (Actual) | Interventional | 2006-05-31 | Completed |
| Randomized, Multi-Center, Phase IV, Comparative Study to Assess the Efficacy and Safety of Combined Peg-Interferon Alpha-2a (40 kD) With Ribavirin Combined Therapy for 48 or 72 Weeks of Treatment and 24 Weeks of Follow-Up in Patients With Chronic Hepatiti [NCT02761629] | Phase 4 | 180 participants (Actual) | Interventional | 2005-04-30 | Completed |
| Phase 2a Study Evaluating a Chemokine-Modulatory Regimen in Patients With Colorectal Cancer Metastatic to the Liver [NCT03403634] | Phase 2 | 19 participants (Actual) | Interventional | 2018-04-19 | Completed |
| Treatment of COVID-19 by Nebulization of Inteferon Beta 1b Efficiency and Safety Study [NCT04469491] | Phase 2 | 75 participants (Actual) | Interventional | 2020-09-20 | Completed |
| Clinical Trial to Compare Topical Interferon Alfa 2b And Mitomycin C in Conjunctival-Corneal Intraepithelial Neoplasia [NCT02199327] | Phase 4 | 18 participants (Actual) | Interventional | 2014-05-31 | Completed |
| A Phase III, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 Versus Boceprevir/Pegylated Interferon/Ribavirin (PR) in Treatment-Naïve and PR Prior Treatment Failure Subjects With Chronic HCV GT1 Inf [NCT02204475] | Phase 3 | 0 participants (Actual) | Interventional | 2014-11-30 | Withdrawn |
| Observational Multicenter Study to Evaluate Influence of Insulin Resistance on the Safety and Efficacy (as Measured by Sustained Virological Response) of Treatment With Any Pegylated Interferon and Ribavirin (Standard of Care) in Different Populations of [NCT00705224] | | 250 participants (Actual) | Observational | 2008-05-31 | Completed |
| A Phase 2A Study of BMS-791325 in Combination With Peg Interferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naïve Subjects With Chronic Hepatitis C Virus Genotype 1 Infection [NCT01193361] | Phase 2 | 39 participants (Actual) | Interventional | 2010-10-31 | Completed |
| Treatment of Chronic Delta Hepatitis With Lonafarnib, Ritonavir and Lambda Interferon [NCT03600714] | Phase 2 | 26 participants (Actual) | Interventional | 2018-08-01 | Completed |
| To Study the Efficacy of 'Tenofovir Pulse and Peg Interferon Alpha 2b' Therapy in HBeAg-positive Patients With Normal ALT - A Randomized Control Trial [NCT02454764] | | 0 participants (Actual) | Interventional | | Withdrawn(stopped due to lack of funds) |
| An Open-label Randomised Controlled Trial on Dual Therapy With Interferon Beta-1b and Clofazimine Combination, as Treatment for COVID-19 Infection [NCT04465695] | Phase 2 | 81 participants (Anticipated) | Interventional | 2020-07-14 | Recruiting |
| A Phase 3, Open-label, Multicenter Study, IBI310 in Combination With IBI308 and IBI308 Compared to High-Dose Interferon In Patients With Acral Melanoma That Has Been Removed by Surgery [NCT04277663] | Phase 3 | 136 participants (Actual) | Interventional | 2020-04-17 | Terminated(stopped due to Due to the company's development strategy adjustment ，Innovent Bioligics decided not to continue the study after consultation with investigators) |
| Worldwide Trends on COVID-19 Research After the Declaration of COVID-19 Pandemic: An Observational Study [NCT04460547] | | 200 participants (Anticipated) | Observational | 2020-07-25 | Not yet recruiting |
| A Phase 2, Randomized, Open Label, Pivotal Study to Evaluate the Efficacy and Safety of HQP1351 in CML CP Patients Who Are Resistant and/or Intolerant to First- and Second-Generation Tyrosine Kinase Inhibitors [NCT04126681] | Phase 2 | 144 participants (Actual) | Interventional | 2019-10-21 | Active, not recruiting |
| Peginterferon Plus Ribavirin Combination Therapy for Hepatitis C Six Months After Onset of Acute Infection [NCT02377856] | Phase 4 | 20 participants (Actual) | Interventional | 2007-06-30 | Completed |
| Immune- and miRNA-response to Recombinant Interferon Beta in Healthy Volunteers and Patients With Relapsing Remitting Multiple Sclerosis [NCT02364986] | Phase 1 | 50 participants (Anticipated) | Interventional | 2015-01-31 | Recruiting |
| Open Controlled Randomized Study of the Efficacy and Safety of Ingaron (Interferon-gamma) in the Treatment of Anogenital Warts (Phase III) [NCT05156541] | Phase 3 | 30 participants (Actual) | Interventional | 2009-05-18 | Completed |
| A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multi-centre Phase IIa Study in Asthma Patients Comparing the Efficacy and Safety of Once Daily Inhaled Interferon Beta-1a to Placebo, Administered for 14 Days After the Onset of Symptoms of [NCT02491684] | Phase 2 | 121 participants (Actual) | Interventional | 2015-07-21 | Completed |
| A Randomised, Double-blind, Placebo-controlled Study, in COPD Patients With and Without a Confirmed Respiratory Virus Infection Assessing Anti-viral Biomarker Responses and Clinical Effects of Inhaled SNG001 Compared to Placebo [NCT03570359] | Phase 2 | 122 participants (Actual) | Interventional | 2018-01-29 | Completed |
| Cross-sectional Retrospective Study of Therapeutic Compliance in Patients With Multiple Sclerosis Treated With Interferon Beta-1b [NCT03408093] | | 120 participants (Actual) | Observational | 2009-02-03 | Completed |
| Neoadjuvant Combination Biotherapy With Pembrolizumab and High Dose IFN-alfa2b in Patients With Locally/Regionally Advanced/Recurrent Melanoma: Safety, Efficacy and Biomarker Study [NCT02339324] | Phase 1 | 31 participants (Actual) | Interventional | 2015-03-06 | Completed |
| AN OPEN LABEL, LONG-TERM EXTENSION STUDY TO INVESTIGATE THE SAFETY OF PF-06823859 ADMINISTERED TO ADULT PARTICIPANTS ≥18 AND ≤80 WITH ACTIVE DERMATOMYOSITIS. [NCT05192200] | Phase 2 | 24 participants (Actual) | Interventional | 2021-12-20 | Active, not recruiting |
| Long-Term Safety Extension Study of ACTIMMUNE® (Interferon γ-1b) in Children and Young Adults With Friedreich's Ataxia [NCT02797080] | Phase 3 | 38 participants (Actual) | Interventional | 2016-06-28 | Completed |
| Czech Pharmaco-epidemiological Real World Data Study Focused on Effectiveness of Different Disease Modifying Drugs [NCT05762003] | | 17,478 participants (Actual) | Observational | 2019-01-01 | Completed |
| Phase 3 Study to Evaluate the Efficacy and Safety of Albumin Interferon Alfa-2b in Combination With Ribavirin Compared With Peginterferon Alfa-2a in Combination With Ribavirin in Interferon Alfa Naive Subjects With CHC Genotype 1. ACHIEVE-1 [NCT00402428] | Phase 3 | 1,331 participants (Actual) | Interventional | 2006-12-31 | Completed |
| Efficacy and Safety of the Combination Vitamin D (Vit D), With Pegylated Interferon Alpha-2b (PEG-IFN)/Ribavirin (RBV) in Egyptian Patients With Untreated Chronic Hepatitis C: A Phase III Randomized Open-label Clinical Trial [NCT02099604] | Phase 3 | 0 participants (Actual) | Interventional | 2014-04-30 | Withdrawn(stopped due to Study objectives were considered as obsolete regarding the new AAD arrival) |
| Prospective, Single-Center, Open Label, Pilot Study of Safety and Efficacy of Triple Anti-Viral Therapy With Pegylated Interferon, Ribavirin, and Boceprevir in Patients With Genotype 1 Chronic HCV With End Stage Renal Disease [NCT02112630] | | 0 participants (Actual) | Interventional | 2013-05-31 | Withdrawn(stopped due to Poor enrollment) |
| BETAEVAL - The New BETACONNECT® Auto-injector: Adherence and EVALuation of MS Patients Treated With Betaferon® [NCT02121444] | | 151 participants (Actual) | Observational | 2014-06-23 | Completed |
| A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose, Dose-Ranging, Parallel-Group Study of PEGylated Interferon Beta-1a (BIIB017) in Healthy Volunteers [NCT02125578] | Phase 1 | 69 participants (Actual) | Interventional | 2008-03-31 | Completed |
| A Multicenter, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Phase 2 Study to Evaluate the Efficacy and Safety of Oral BIIB061 as Add-On Therapy to Interferon-Beta 1 or Glatiramer Acetate Therapies in Relapsing Multiple Sclerosis [NCT04079088] | Phase 2 | 0 participants (Actual) | Interventional | 2021-06-30 | Withdrawn(stopped due to Decision to discontinue BIIB061 program was based on lack of stronger preclinical effects of BIIB061 on remyelination relative to opicinumab, that showed limited clinical efficacy in phase 2 clinical studies. This was not related to safety concerns.) |
| Comparative Trial of the Pharmacokinetics and Pharmacodynamics of Intramuscularly Injected CinnoVex® and Avonex® in Healthy Volunteers [NCT03614715] | Phase 1 | 40 participants (Actual) | Interventional | 2017-11-27 | Completed |
| Retrospective Data Collection on Betaferon Use in Children and Adolescents With Multiple Sclerosis [NCT03577977] | | 70 participants (Actual) | Observational | 2008-06-01 | Completed |
| A Phase Ib Study of The Safety And Pharmacology of Atezolizumab (Anti-Pd-L1 Antibody) Administered With Ipilimumab, Interferon-Alpha, or Other Immune-Modulating Therapies in Patients With Locally Advanced or Metastatic Solid Tumors [NCT02174172] | Phase 1 | 158 participants (Actual) | Interventional | 2014-08-18 | Completed |
| Open Label, Study to Determine the Pharmacokinetic Interactions of Steady State Tipranavir/Ritonavir (500/200 mg) and Steady State Ribavirin and Pegylated Interferon Alfa 2a in HIV Negative, HCV Infected Subjects With Mild Hepatic Impairment and the Pharm [NCT02259855] | Phase 1 | 36 participants (Actual) | Interventional | 2006-01-31 | Completed |
| An Open-label, Single Arm, Phase III Study to Assess the Self-administration of AOP2014 Using a Pre-filled Pen, Developed for the Treatment of Polycythemia Vera Patients [NCT02523638] | Phase 3 | 30 participants (Anticipated) | Interventional | 2015-07-31 | Completed |
| A Phase II, Randomized, Multicenter, Placebo-Controlled, Double-Blind, Parallel-Group Study, With an Open-Label Extension, to Evaluate the Efficacy, Safety, and Pharmacokinetics of E5501 in Subjects With Chronic Hepatitis C Virus Related Thrombocytopenia [NCT01355289] | Phase 2 | 65 participants (Actual) | Interventional | 2011-11-30 | Completed |
| A Phase III Double-blind, Randomised, Parallel-Group Comparison of the Efficacy and Safety of FP-1201-lyo (Recombinant Human IFN Beta-1a) and Placebo in the Treatment of Patients With Moderate or Severe Acute Respiratory Distress Syndrome [NCT02622724] | Phase 3 | 301 participants (Actual) | Interventional | 2015-12-23 | Terminated(stopped due to Day 90 results indicate IMP did not reduce mortality or ventilator free days) |
| A Pilot Study of IFN-γ to Treat Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) That Has Relapsed After Allogeneic Hematopoietic Stem Cell Transplantation [NCT04628338] | Early Phase 1 | 8 participants (Actual) | Interventional | 2021-03-08 | Completed |
| Multi-centre, Adaptive, Randomized Trial of the Safety and Efficacy of Treatments of COVID-19 in Hospitalized Adults [NCT04315948] | Phase 3 | 1,552 participants (Actual) | Interventional | 2020-03-22 | Completed |
| Phase II Study of Capecitabine and Interferon-Alpha in Metastatic Renal Cell Carcinoma Patients With Failure on Interleukin-2 Based Regimens [NCT00591188] | Phase 2 | 49 participants (Anticipated) | Interventional | 2006-12-31 | Completed |
| A Phase 2B, Randomized Study to Evaluate the Safety and Efficacy of Pegylated Interferon Lambda (BMS-914143) Administered With Ribavirin Plus a Single Direct Antiviral Agent (BMS-790052 or BMS-650032) Versus Pegasys Administered With Ribavirin (Part A) an [NCT01309932] | Phase 2 | 165 participants (Actual) | Interventional | 2011-03-31 | Completed |
| Better Identification of Latent Tuberculosis Infection Among Israeli Young Adults by Comparison Skin Tests and Interferon Gamma Releasing Assays (IGRA) [NCT02073669] | | 115 participants (Actual) | Interventional | 2014-03-31 | Completed |
| A Pilot Study of Neurocognitive Function in Patients Treated With Adjuvant Interferon Alpha-2b for High-Risk Melanoma [NCT02074605] | | 36 participants (Actual) | Observational | 2008-07-31 | Completed |
| Randomized, Controlled, Open Label, Phase 2 Clinical Trial of Interferon-β-1a (IFNβ-1a) in COVID-19 Patients [NCT04449380] | Phase 2 | 56 participants (Actual) | Interventional | 2020-11-02 | Terminated(stopped due to Futility) |
| Pilot Study to Assess Efficacy and Safety of a Quadruple Therapy With Asunaprevir, Daclatasvir, Ribavirin and Pegylated Interferon Alpha-2a in HCV Genotype 4-infected Patients Non-responders to Pegylated Interferon-Ribavirin Regimen [NCT02107365] | Phase 2 | 60 participants (Actual) | Interventional | 2013-11-30 | Completed |
| A Randomized, Multi Center, Phase IIIb Open-label Study to Evaluate the Efficacy of Sequential Therapy of Peginterferon Alfa-2a(Pegasys(TM)) Following Entercavir Compared With Peginterferon Alfa-2a Monotherapy in Patient With HBeAg Positive Chronic Hepati [NCT01220596] | Phase 3 | 228 participants (Anticipated) | Interventional | 2010-06-30 | Recruiting |
| Prospective Multicenter, Non Interventional Study to Evaluate the Patient's Characteristics Associated With Adherence to Treatment Regimen by Betaferon in the BetaPlus Program [NCT01076595] | | 73 participants (Actual) | Observational | 2010-05-31 | Completed |
| A Prospective Analysis of MS Patients After Starting or Restarting Baseline Treatment With Interferon Beta 1a After the Use of Escalation Treatment [NCT01142518] | | 86 participants (Actual) | Observational | 2005-07-31 | Completed |
| An Open, Multi-center Clinical Study of Combination Therapy With Tenofovir Disoproxil Fumarate and Peginterferon Alpha 2a in Nucleos(t)Ide Analogs Experienced Patients With HBV Related Hepatic Fibrosis. [NCT03957629] | | 186 participants (Anticipated) | Interventional | 2019-11-06 | Recruiting |
| A Phase II Study of Peg-Interferon Alpha-2B (Peg-Intron(TM)) and Thalidomide in Adults With Recurrent High-Grade Gliomas [NCT00047879] | Phase 2 | 7 participants (Actual) | Interventional | 2002-10-31 | Completed |
| A Phase II, Randomized, Multi-center, Two Part Study of the Safety and Efficacy of Double-blind, Placebo-controlled INX-08189 in Adjunctive Treatment With Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Study Part A, and Open-label INX-08189 [NCT01425970] | Phase 2 | 210 participants (Actual) | Interventional | 2012-05-31 | Terminated(stopped due to Termination of study was due to safety reasons) |
| A Phase 3, Randomized, Double-Blind, Controlled Study Evaluating the Efficacy and Safety of Peginterferon Lambda-1a, With and Without Daclatasvir, Compared to Peginterferon Alfa-2a, Each in Combination With Ribavirin, in the Treatment of Naïve Genotype 2 [NCT01616524] | Phase 3 | 880 participants (Actual) | Interventional | 2012-07-31 | Completed |
| Clinical Trial of the Efficacy, Dosing, Safety and Tolerability of Y- Shaped Pegylated Interferon (YPEG-IFNα-2a) Plus Ribavirin in Egyptian Patients With Untreated Chronic Hepatitis C [NCT01327729] | Phase 2/Phase 3 | 300 participants (Anticipated) | Interventional | 2010-11-30 | Recruiting |
| A Pilot Multi-Center, Open-Label, Assessor Blinded, Prospective Profiling Study in MS Subjects Treated With AVONEX®, MS Subjects Naïve to Treatment, and Healthy Control Subjects [NCT00913666] | Phase 4 | 121 participants (Actual) | Interventional | 2002-11-30 | Completed |
| Neoadjuvant Treatment of Locoregional Metastases in Malignant Melanoma (AJCC Stage IIIB/C) With Multiferon: a Phase IIa DeCOG Trial [NCT01341158] | Phase 2 | 42 participants (Actual) | Interventional | 2011-04-30 | Completed |
| Phase I/II, Multicenter, Randomized, Open,Active-Controlled, ClinicalTrial to Evaluate PK, PD, Safety and Tolerability Of Interferon Alfa 5, S.C. 3 Times Per Week, For 29 Days, To Treat-Experienced Pat. With Genotype-1 Chronic Hepatitis C [NCT01121731] | Phase 1/Phase 2 | 70 participants (Actual) | Interventional | 2010-05-31 | Completed |
| A Pilot Study of Repeated Dose Intrapleural Adenoviral-Mediated Interferon-Alpha (SCH 721015, Ad.hIFN-a2b) Gene Transfer for Malignant Pleural Mesothelioma [NCT01212367] | Phase 1 | 13 participants (Actual) | Interventional | 2009-02-28 | Completed |
| Differences in Evoked Intracellular Interferon Signaling Pathways Using Single Cell Phosphoprotein Profiling [NCT01217359] | Phase 1 | 22 participants (Actual) | Interventional | 2010-05-31 | Completed |
| Pegylated Interferon Alfa-2a Plus Ribavirin for Patients With Chronic Hepatitis c Virus on Opioid Pharmacotherapy: Virological and Psychological Outcomes [NCT01120795] | Phase 4 | 55 participants (Actual) | Interventional | 2004-02-29 | Completed |
| A Randomised, Double-blind, Placebo-controlled Phase II Study, Comparing the Efficacy and Safety of Inhaled SNG001 to Placebo Administered to Asthmatic Subjects After the Onset of a Respiratory Viral Infection for the Prevention or Attenuation of Asthma S [NCT01126177] | Phase 2 | 300 participants (Actual) | Interventional | 2010-03-31 | Completed |
| National Multicenter, Controlled, Single-blind Study With Two Parallel Groups Evaluating the Safety and Efficacy of Sequential Treatment With Mitoxantrone and Interferon Beta-1a (REBIF 44mg 3 Times / Week) Versus Interferon Alone in Patients With Strong R [NCT02937285] | Phase 3 | 35 participants (Actual) | Interventional | 2010-12-06 | Completed |
| Phase III Prospective Randomized Comparison of Depot Octreotide Plus Interferon Alpha Versus Depot Octreotide Plus Bevacizumab (NSC #704865) in Advanced, Poor Prognosis Carcinoid Patients [NCT00569127] | Phase 3 | 427 participants (Actual) | Interventional | 2007-12-01 | Active, not recruiting |
| A Multicenter, Open-Label Immunogenicity and Safety Study of a Serum-Free Pre-Formulated Solution of AVONEX (Interferon Beta-1a) Administered Intramuscularly to Patients With Relapsing/Remitting Multiple Sclerosis [NCT00912860] | Phase 2 | 155 participants (Actual) | Interventional | 2003-01-31 | Completed |
| Portuguese BetaPlus Survey - Observational Study to Assess Drug Adherence in Patients With Multiple Sclerosis (MS) After Conversion to Betaferon by Using Elements of the BetaPlus Program [NCT01235455] | | 10 participants (Actual) | Observational | 2007-08-31 | Completed |
| Therapy of the Chronic Multiple Sclerosis With Interferon-beta 1a (Rebif®) [NCT01142557] | | 522 participants (Actual) | Observational | 2004-06-30 | Completed |
| Pilot Study of Interferon Alpha Lozenges Plus Oseltamivir in the Treatment of Influenza A Infection [NCT01146535] | Phase 2 | 40 participants (Actual) | Interventional | 2011-01-31 | Completed |
| Phase IIII Study of a Therapeutic Vaccine Candidate Containing Hepatitis B Virus (HBV) Core Antigen (HBcAg) and HBV Surface Antigen (HBsAg) for Treatment of Patients With Chronic HBV Infection [NCT01374308] | Phase 3 | 160 participants (Anticipated) | Interventional | 2011-06-30 | Active, not recruiting |
| Evaluation of Risk Factors for Premature Discontinuation of Injection Treatment With Betaferon in Patients With Relapsing Forms of Multiple Sclerosis [NCT01184833] | | 852 participants (Actual) | Observational | 2008-09-30 | Completed |
| A Phase 1b/2a, Open-label,Randomized, Safety, Tolerability, Dose Finding, Pharmacokinetic/Pharmacodynamic, and Preliminary Efficacy Study of Subcutaneous Hanferon™ in Combination With Ribavirin in Treatment-naïve Subjects With Genotype 1 Hepatitis C [NCT01194037] | Phase 1/Phase 2 | 30 participants (Actual) | Interventional | 2011-06-30 | Completed |
| Interferon-gamma as Adjunctive Therapy in Chronic Pulmonary Aspergillosis: a Randomised Feasibility Study [NCT05653193] | Phase 2 | 50 participants (Anticipated) | Interventional | 2024-01-31 | Not yet recruiting |
| Multicenter Study on Efficacy of New Therapeutic Schedules With Peg-Interferon alpha2b and Ribavirin in Patients With Genotype 3 Chronic HCV( Hepatitis C Virus) Infection [NCT01121705] | Phase 3 | 360 participants (Actual) | Interventional | 2007-01-31 | Completed |
| Intravenous Interferon During the Anhepatic Phase of Liver Transplantation and Prevention of Recurrence of Hepatitis C Virus [NCT01192698] | | 15 participants (Actual) | Interventional | 2009-10-31 | Completed |
| BetaPlus Survey - Observational Study to Assess Drug Adherence in Patients With Multiple Sclerosis After Conversion to Betaferon® by Using Elements of the BetaPlus Program [NCT01233245] | | 1,077 participants (Actual) | Observational | 2004-04-30 | Completed |
| Safety and Efficacy of Locally Manufactured Pegylated Interferon in Hepatitis C Patients [NCT01137383] | Phase 3 | 108 participants (Actual) | Interventional | 2007-12-31 | Completed |
| Therapy Optimisation Using High-frequency and High-dosage Administration of Interferon-beta (Rebif®) in MS Patients. Case Series for Adjustment of Treatment Strategy and Its Monitoring [NCT01142453] | | 231 participants (Actual) | Observational | 2005-05-31 | Completed |
| A Phase II Study Of Pegylated Interferon ALFA-2b in Children With Recurrent or Refractory and Radiographically or Clinically Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas [NCT02343224] | Phase 2 | 9 participants (Actual) | Interventional | 2014-11-30 | Completed |
| A Double-Blind, Placebo-controlled Phase II Study to Assess the Efficacy and Safety of Romiplostim, Administered Once Weekly to Thrombocytopenic Hepatitis C (HCV) Infected Subjects Who Are Not Candidates for Antiviral Treatment With Pegylated Interferon a [NCT01153919] | Phase 2 | 27 participants (Actual) | Interventional | 2010-06-30 | Terminated(stopped due to Approval of several new agents for the treatment of HCV infection would mitigate the future need for interferon HCV treatment) |
| A Study to Evaluate the Efficacy and Safety of Clevudine and Peg-interferon in Sequence Compared With Clevudine Alone in the Patients With HBeAg(+) Chronic Hepatitis B or Clevudine and Peg-interferon Sequential Treatment in Patients With Chronic Hepatitis [NCT01264367] | Phase 4 | 60 participants (Anticipated) | Interventional | 2008-12-31 | Completed |
| A Randomized Phase II Trial of IL-2/IFN-α Plus Bevacizumab Versus IL-2/IFN-α in Metastatic Renal Cell Carcinoma (mRCC) - Danish Renal Cancer Group (DARENCA) Study-1 [NCT01274273] | Phase 2 | 118 participants (Anticipated) | Interventional | 2009-10-31 | Active, not recruiting |
| the Investigation Into Beneficial Effects of High-dose Interferon Beta 1-a, Compared to Low-dose Interferon Beta 1-a in Moderate to Severe Covid-19 [NCT04521400] | Phase 2 | 100 participants (Anticipated) | Interventional | 2020-08-20 | Not yet recruiting |
| A Phase 3 Study With Asunaprevir and Daclatasvir (DUAL) for Null or Partial Responders to Peginterferon Alfa and Ribavirin (P/R), Intolerant or Ineligible to P/R Subjects and Treatment-Naive Subjects With Chronic Hepatitis C Genotype 1b Infection [NCT01581203] | Phase 3 | 748 participants (Actual) | Interventional | 2012-05-31 | Completed |
| Open-Label Extended Administration of SCH 54031 (PEG Interferon Alfa-2b/PEG Intron) in Subjects With Solid Tumors [NCT03554005] | Phase 1 | 29 participants (Actual) | Interventional | 1997-12-29 | Completed |
| Therapeutic Effect of Topical Estrogen and Human Interferon Alpha 2b Vaginal Effervescent Capsules in Perimenopausal and Postmenopausal Women With High-risk HPV Infection [NCT05863975] | Phase 4 | 150 participants (Anticipated) | Interventional | 2023-07-01 | Not yet recruiting |
| A Pilot Study Of Interferon Alpha 2b Plus Ribavirin In The Treatment Of Patients With Chronic Hepatitis B [NCT00275938] | Phase 2/Phase 3 | 120 participants | Interventional | 1998-10-31 | Completed |
| Phase II Trial Of Interferon-B In Patients With Metastatic Cutaneous Melanoma And Metastatic Ocular Melanoma [NCT00085306] | Phase 2 | 21 participants (Actual) | Interventional | 2004-04-30 | Completed |
| Observational Prospective Registry of the Efficacy, Safety, and Adherence to Therapy of Infergen® (Interferon Alfacon 1) in Patients Chronically Infected With Hepatitis C Virus [NCT00951223] | | 0 participants (Actual) | Observational | 2009-08-31 | Withdrawn(stopped due to Lack of Enrollment) |
| A Phase 1 Double-Blind, Randomised, Two-Treatment Cross-over Study Comparing the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PF530 and Betaferon Administered by Subcutaneous Injection in Healthy Adult Volunteers [NCT02474134] | Phase 1 | 12 participants (Actual) | Interventional | 2015-03-31 | Completed |
| Phase I Biochemotherapy With Cisplatin, Temozolomide, With Increasing Doses of Abraxane, Combined With Interleukin-2 and Interferon in Patients With Metastatic Melanoma [NCT00970996] | Phase 1 | 10 participants (Actual) | Interventional | 2009-09-30 | Completed |
| Multicenter, Double-blind, Randomized, Parallel-group, Monotherapy, Active-control Study to Determine the Efficacy and Safety of Daclizumab High Yield Process (DAC HYP) Versus Avonex® (Interferon β 1a) in Patients With Relapsing-Remitting Multiple Scleros [NCT01064401] | Phase 3 | 1,841 participants (Actual) | Interventional | 2010-05-31 | Completed |
| A Three Arm, Randomized, Double Blind, Placebo Controlled, Multicenter, Phase II Study to Evaluate the Efficacy of Vigantol® Oil as Add on Therapy in Subjects With Relapsing Remitting Multiple Sclerosis Receiving Treatment With 44mg Tiw of Rebif® [NCT01285401] | Phase 2 | 260 participants (Actual) | Interventional | 2011-02-28 | Completed |
| Combination Immunotherapy With Interferon-gamma and Nivolumab for Patients With Advanced Solid Tumors: A Phase 1 Study [NCT02614456] | Phase 1 | 26 participants (Actual) | Interventional | 2015-12-11 | Completed |
| A Phase III Study With Long-Term Follow-Up of Zidovudine Versus Zidovudine and Alpha-Interferon Versus Alpha-Interferon in Patients With Early HIV Infection [NCT01125228] | | 180 participants (Actual) | Observational | 1988-10-19 | Active, not recruiting |
| Randomized Trial of Pegylated Interferon Alfa-2a Versus Hydroxyurea Therapy in the Treatment of High Risk Polycythemia Vera (PV) and High Risk Essential Thrombocythemia (ET) [NCT01259856] | Phase 3 | 168 participants (Actual) | Interventional | 2011-09-30 | Completed |
| A Phase 2B Pilot Study of Short-Term Treatment of BMS-790052 in Combination With Peg-Interferon Alfa-2a and Ribavirin in Treatment Naive Subjects With Chronic Hepatitis C Genotype 2 or 3 Infection [NCT01257204] | Phase 2 | 196 participants (Actual) | Interventional | 2010-12-31 | Completed |
| A Phase IIa Randomized, Partially Blinded Trial of Telaprevir (VX-950) in Treatment-Naive Subjects With Chronic Genotype 4 Hepatitis C Infection [NCT00580801] | Phase 2 | 24 participants (Actual) | Interventional | 2008-01-31 | Completed |
| Antiviral Effect and Safety of Once Daily BI 201335 NA in Hepatitis C Virus Genotype 1 Infected Treatment-naive Patients for 12 or 24 Weeks as Combination Therapy With Pegylated Interferon-alpha 2a and Ribavirin (Randomised, Open Label, Phase II) [NCT00984620] | Phase 2 | 160 participants (Actual) | Interventional | 2009-09-30 | Completed |
| Fludarabine, Mitoxantrone, and Dexamethasone (FND) Plus Chimeric Anti-CD20 Monoclonal Antibody (Rituximab) for Stage IV Indolent Lymphoma [NCT00577993] | Phase 3 | 210 participants (Actual) | Interventional | 1998-03-16 | Completed |
| Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 3 - Interferon Beta-1A and Peginterferon Beta-1A [NCT04183491] | Phase 1 | 84 participants (Actual) | Interventional | 2020-02-28 | Completed |
| Clinical and Virological Efficacy of Pegylated Interferon Alpha in the Treatment of Rhinovirus Infection in Patients With Primary Hypogammaglobulinemia: Randomized Controlled Trial [NCT02661477] | Phase 2 | 20 participants (Anticipated) | Interventional | 2016-05-31 | Not yet recruiting |
| Interferon α After Prophylactic Donor Lymphocyte Infusion for the Relapse Prevention After Hematopoietic Stem Cell Transplantation [NCT02568241] | Phase 1/Phase 2 | 42 participants (Anticipated) | Interventional | 2015-12-31 | Recruiting |
| Therapeutic Safety and Efficacy of REP 2139 (REP 9AC') in HBV Infected Patients [NCT02646189] | Phase 1/Phase 2 | 12 participants (Actual) | Interventional | 2011-08-31 | Completed |
| Double-Blind, Randomized, Placebo-Controlled, Single Ascending and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Target Engagement of BMS-986184 in Healthy Subjects and to Evaluate the Safety, Efficacy, Pharmacokinetics, [NCT02864264] | Phase 1 | 7 participants (Actual) | Interventional | 2016-09-14 | Terminated(stopped due to Adverse change in the risk/benefit) |
| Phase I Trial of Systemic Administration of Vesicular Stomatitis Virus Genetically Engineered to Express NIS and Human Interferon, in Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, Lymphomas, or Histiocytic/Dendritic Cell N [NCT03017820] | Phase 1 | 120 participants (Anticipated) | Interventional | 2017-04-04 | Recruiting |
| A Clinical Study of SCH 54031 as Monotherapy in IFN-treated Patients With Chronic Hepatitis C [NCT00686881] | Phase 3 | 261 participants (Actual) | Interventional | 2006-12-31 | Terminated(stopped due to This study was terminated due to low enrollment) |
| Efficacy of Switch or Sequential Combination Therapy of Pegylated Interferon Alfa-2a in Chronic Hepatitis B Patients With Low HBsAg and HBeAg Titers After Long-term Entecavir Therapy: A Multicenter, Prospective Cohort Study [NCT02589652] | | 294 participants (Anticipated) | Observational | 2015-10-31 | Not yet recruiting |
| A Randomized Phase III Study On The Effect Of Thalidomide Combined With Adriamycin, Dexamethasone (AD) And High Dose Melphalan In Patients With Multiple Myeloma [NCT00028886] | Phase 3 | 450 participants (Anticipated) | Interventional | 2001-03-31 | Active, not recruiting |
| Phase 1/2A Study of Rintatolimod and IFN Alpha Regimen in Cancer Patients With COVID-19 [NCT04379518] | Phase 1/Phase 2 | 64 participants (Anticipated) | Interventional | 2020-11-17 | Suspended(stopped due to working on revision to protocol) |
| Betaferon Prospective Study on Adherence, Coping and Nursing Support [NCT00787657] | | 1,723 participants (Actual) | Observational | 2008-06-30 | Completed |
| Randomized, Open, Blank Control Study on the Efficacy and Safety of Recombinant Human Interferon α1β in the Treatment of Patients With New Type of Coronavirus Infection in Wuhan [NCT04293887] | Early Phase 1 | 328 participants (Anticipated) | Interventional | 2020-03-01 | Not yet recruiting |
| The Activity of Nitazoxanide in Addition to Peginterferon Alfa-2a and Ribavirin in Chronic Hepatitis C Treatment-Naive Genotype 1 Subjects With HIV Coinfection [NCT00991289] | Phase 2 | 68 participants (Actual) | Interventional | 2010-01-31 | Completed |
| Non-insulin-dependent Diabetes Mellitus and Insulin Resistance in Chronic Hepatitis C Patients Treated With Combination Therapy With Pegylated Interferon and Ribavirin in Taiwan [NCT00687999] | | 400 participants (Actual) | Interventional | 2005-12-31 | Completed |
| Chi3L1: A Marker of Efficacy of Platform Treatments in Relapsing-onset Multiple Sclerosis: A Prognostic Study on Existing Clinical Data and Biological Samples [NCT04289675] | | 63 participants (Actual) | Observational [Patient Registry] | 2012-01-01 | Completed |
| A Phase 2b, Safety and Efficacy Study of Boceprevir in Patients Coinfected With HIV and Hepatitis C (Protocol No. P05411) [NCT00959699] | Phase 2 | 99 participants (Actual) | Interventional | 2009-11-30 | Completed |
| Phase 2B, Partially Blinded, Randomized Study in Treatment Naive HCV G1 to Compare the Efficacy, Safety, and Tolerability of Three Doses of Locteron Plus Ribavirin Given Bi-weekly in Comparison With PEG-Intron Plus Ribavirin Given Weekly [NCT00863239] | Phase 2 | 116 participants (Actual) | Interventional | 2009-03-31 | Completed |
| Long-term Extension of the Multinational, Double-blind, Placebo Controlled Studies PDY6045 and PDY6046 to Document the Safety of Teriflunomide When Added to Treatment With Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis With Rela [NCT00811395] | Phase 2 | 182 participants (Actual) | Interventional | 2007-10-31 | Completed |
| Adoptive TIL Therapy With Low-dose IFN-alpha Plus Anti-PD1 in Metastatic Melanoma [NCT03638375] | Phase 1/Phase 2 | 34 participants (Anticipated) | Interventional | 2018-07-31 | Active, not recruiting |
| A Phase III, Randomised, Double-blind and Placebo Controlled Study of Once Daily BI 201335, 240 mg for 12 or 24 Weeks in Combination With Pegylated interferon-a (PegIFNa) and Ribavirin (RBV) in Patients With Genotype 1 Chronic Hepatitis C Infection Who Fa [NCT01358864] | Phase 3 | 678 participants (Actual) | Interventional | 2011-06-30 | Completed |
| Open-label, Randomized, 2-arm, Active Comparator Study to Evaluate Safety and Tolerability in Patients With Relapsing Multiple Sclerosis Transitioning From Standard-of-care Subcutaneous Interferon Therapy to Peginterferon Beta-1a (BIIB017) [NCT02234869] | Phase 4 | 0 participants (Actual) | Interventional | 2014-10-31 | Withdrawn(stopped due to Due to a change in Biogen Idec's medical research plans.) |
| A Study of the Safety and Efficacy of Combination Treatment With REP 2139-Ca and Pegasys™ in Patients With Hepatitis B / Hepatitis D Co-infection [NCT02233075] | Phase 2 | 12 participants (Actual) | Interventional | 2014-09-30 | Completed |
| A Phase 3, Open-Label Study With Asunaprevir and Daclatasvir Plus Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) (P/R) (QUAD) for Subjects Who Are Null or Partial Responders to Peginterferon Alfa 2a or 2b Plus Ribavirin With Chronic Hepatitis C G [NCT01573351] | Phase 3 | 398 participants (Actual) | Interventional | 2012-05-31 | Completed |
| A Phase II, Multicentre, Open, Randomised, Dose Ranging Study to Investigate the Efficacy of Combination Therapy Containing Dacarbazine (DTIC) Plus Low Dose Interferon Alpha (aIFN) Plus Thymosin a1 Versus Both DTIC Plus Thymosin a1 and DTIC Plus aIFN in P [NCT00911443] | Phase 2 | 488 participants (Actual) | Interventional | 2002-07-31 | Completed |
| A Phase II Study of EC17 (Folate-hapten Conjugate) in Patients With Progressive Metastatic Renal Cell Carcinoma [NCT00485563] | Phase 2 | 12 participants (Actual) | Interventional | 2007-06-30 | Terminated(stopped due to Changes in treatment paradigm resulted in a lower than expected rate of accrual.) |
| A Phase I Open-Label, Non-Randomized, Dose-Escalation Study of rSIFN-co in Subjects With Advanced Solid Tumors and With an Expansion Cohort at Recommended Dose (RD) in Subjects With Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Melanoma, Hepatocellula [NCT02387307] | Phase 1 | 42 participants (Actual) | Interventional | 2013-07-31 | Completed |
| Phase3 Study to Evaluate the Efficacy and Safety of AlbuminInterferon in Combination With Ribavirin Compared With Peginterferon in Combination With Ribavirin in Interferon Alfa Naive Subjects With CHC Genotype 2/3. [NCT00411385] | Phase 3 | 933 participants (Actual) | Interventional | 2007-02-28 | Completed |
| PFL-Alpha Chemotherapy Followed by Surgery or FHX for Early Stage Esophageal Cancer - A Pilot Project [NCT00004897] | Phase 2 | 0 participants | Interventional | 1999-10-31 | Terminated(stopped due to Institutional Review Board requested termination - all patients deceased and no new accrual.) |
| Phase II Study of Multimodality Therapy in Mantle Cell Lymphoma [NCT00004231] | Phase 2 | 0 participants | Interventional | 1999-10-31 | Completed |
| A Phase 1b, Randomized, Multi-center, Open-label Study of a Conditionally Replicative Adenovirus (DNX-2401) and Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma (TARGET-I) [NCT02197169] | Phase 1 | 37 participants (Actual) | Interventional | 2014-09-11 | Completed |
| Bioavailability, Pharmacokinetic and Pharmacodynamic Profile of Interferon Beta-1a (Bioferon®) Administered i.v. and s.c. as Single Doses to Healthy Subjects [NCT02515695] | Phase 1 | 12 participants (Actual) | Interventional | 2005-05-31 | Completed |
| A Multinational, Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Control (Rater Blinded) Study, to Evaluate The Efficacy, Safety And Tolerability Of 2 Doses Of Oral Administration Of Laquinimod (0.6 mg/Day Or 1.2 mg/Day) Compared to Interfer [NCT01975298] | Phase 3 | 0 participants (Actual) | Interventional | 2014-01-31 | Withdrawn(stopped due to Business Decision) |
| An Open-label Randomised Controlled Trial on IFN Beta-1b and Ribavirin Combination, as Treatment for Covid-19 Infection [NCT04494399] | Phase 2 | 96 participants (Anticipated) | Interventional | 2020-07-29 | Recruiting |
| Extension Protocol for Patients With Chronic Myelogenous Leukemia, Malignant Melanoma or Renal Cell Carcinoma That Have Responded to Treatment With Pegylated-Interferon α-2a or Roferon-A® in Prior Clinical Studies [NCT02829775] | Phase 2/Phase 3 | 9 participants (Actual) | Interventional | 2004-01-31 | Completed |
| A Randomized Controlled Study Evaluating the Efficacy and Safety of Pegylated Interferon α-2b in Combination With Ruxolitinib vs. Pegylated Interferon α-2b Monotherapy for Treating Hydroxyurea-resistant/Intolerant Polycythemia Vera [NCT05870475] | Phase 2 | 94 participants (Anticipated) | Interventional | 2023-05-30 | Recruiting |
| A 18-month, Open-label, Rater-blinded, Randomized, Multi-center, Active-controlled, Parallel-group Pilot Study to Assess Efficacy and Safety of Fingolimod in Comparison to Interferon Beta 1b in Treating the Cognitive Symptoms Associated to Relapsing-remit [NCT01333501] | Phase 4 | 151 participants (Actual) | Interventional | 2011-05-31 | Completed |
| Tolerability and Quality of Life in Patients With Multiple Sclerosis Switched to Intramuscular Interferon Beta 1a Autoinjector (Avonex® PenTM) [NCT02076841] | | 40 participants (Actual) | Observational | 2013-07-31 | Completed |
| Randomized, Multicentric, Partially Double-Blinded Placebo-Controlled Phase II Study for Examining the Influence of Ribavirin on the Initial Virological Response With Treatment of Peginterferon Alfa-2a (40KD) and Ribavirin With a Six Week Pretreatment-Pha [NCT02716779] | Phase 2 | 68 participants (Actual) | Interventional | 2007-04-30 | Completed |
| Prospective Randomized Open-label Comparative Study of the Use of Intranasal Form of Interferon Gamma Human Recombinant in Patients for the Prevention of Acute Respiratory Viral Infections, Including COVID-19 [NCT05054114] | | 630 participants (Actual) | Interventional | 2020-12-21 | Completed |
| Effect and Safety of Recombinant Human Interferon α-2b Spray on Herpangina in Pediatric Patients [NCT03266601] | Phase 4 | 668 participants (Actual) | Interventional | 2016-06-01 | Completed |
| Tolerance-Induction With Dendritic Cells Treated With Vitamin-D3 and Loaded With Myelin Peptides, in Multiple Sclerosis Patients (TOLERVIT-MS) [NCT02903537] | Phase 1 | 16 participants (Anticipated) | Interventional | 2017-07-06 | Recruiting |
| Interferon Alpha (NSC# 377523) Plus 13-Cis-Retinoic Acid Modulation Of BCL-2 Plus Paclitaxel For Recurrent Small Cell Lung Cancer [NCT00062010] | Phase 2 | 37 participants (Actual) | Interventional | 2004-05-26 | Completed |
| Treatment of Follicular Non-Hodgkin's Lymphoma With High Dose Therapy and Stem Cell Support Followed by Consolidative Immunotherapy With Rituximab and Alpha Interferon [NCT03069248] | Phase 2 | 36 participants (Actual) | Interventional | 2000-06-01 | Completed |
| Evaluation of a CD4/CD8+ Interferon Gamma Release Assay for Monitoring Anti-Tuberculosis Treatment [NCT05724212] | | 220 participants (Actual) | Observational | 2017-01-27 | Active, not recruiting |
| A Randomized, Active-Controlled, Dose-Ranging Estimation Study to Evaluate the Safety, Tolerability, and Efficacy of Different Regimens of MK-5172 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Treatment-Naïve Patients With Ch [NCT01353911] | Phase 2 | 368 participants (Actual) | Interventional | 2011-06-27 | Completed |
| AVASTIN® First Line in Metastatic Renal Cancer [NCT02627144] | | 365 participants (Actual) | Observational | 2008-01-31 | Completed |
| A Phase II Trial of MK-3475 (Pembrolizumab) and Interferon Gamma 1-b Combination Immunotherapy in Patients With Previously Treated Mycosis Fungoides and Sezary Syndrome (Treatment Group 1) and in Patients With Advanced Synovial Sarcoma (Treatment Group 2) [NCT03063632] | Phase 2 | 28 participants (Actual) | Interventional | 2017-12-14 | Completed |
| Comparative Effectiveness and Tolerability of Boceprevir vs Telaprevir and Re-assessment of Treatment Duration in Patients With Chronic Hepatitis C [NCT02113631] | | 50 participants (Actual) | Interventional | 2011-09-30 | Completed |
| A Phase 1 Study to Evaluate Safety, Toxicity, and Potential Mechanisms of Interferon Gamma-primed Mesenchymal Stromal Cells (MSCs) for Moderate-to-severe Persistent Asthma [NCT05035862] | Phase 1 | 12 participants (Anticipated) | Interventional | 2022-03-16 | Recruiting |
| Assessment of the Immune Response to SARS-CoV-2/COVID-19 Vaccination in Patients With Sarcoidosis [NCT05089565] | | 101 participants (Actual) | Observational [Patient Registry] | 2021-12-01 | Completed |
| Randomized, Open-Label Study of the Bria-IMT Regimen and Check Point Inhibitor vs Physicians' Choice in Advanced Metastatic Breast Cancer. [NCT06072612] | Phase 3 | 404 participants (Anticipated) | Interventional | 2023-10-20 | Recruiting |
| Phase I/IIa Clinical Trial Evaluating the Safety and Efficacy of Rintatolimod Combined With IFNα2b (Bioferon®) to Enhance the Effectiveness of Pembrolizumab in Patients With Metastatic Triple Negative Breast Cancer [NCT05756166] | Phase 1/Phase 2 | 12 participants (Anticipated) | Interventional | 2023-12-30 | Not yet recruiting |
| Interferon-α1b (IFN-α1b) Combined With Toripalimab and Anlotinib Hydrochloride in Patients With Advanced Unresectable Melanoma [NCT05539118] | Phase 1/Phase 2 | 48 participants (Anticipated) | Interventional | 2022-09-30 | Not yet recruiting |
| COVID-19 Prevention and Treatment in Cancer; a Sequential Multiple Assignment Randomised Trial; C-SMART Study. [NCT04534725] | Phase 3 | 441 participants (Actual) | Interventional | 2020-12-17 | Completed |
| Interferon α for the Therapy of Minimal Residual Disease Following Hematopoietic Stem Cell Transplantation [NCT02185261] | | 81 participants (Anticipated) | Interventional | 2014-06-30 | Recruiting |
| A Randomized, Double-Blind, Double-Dummy, Parallel-Group Study To Evaluate the Efficacy and Safety of Ocrelizumab in Comparison to Interferon Beta-1a (Rebif) in Patients With Relapsing Multiple Sclerosis [NCT01412333] | Phase 3 | 835 participants (Actual) | Interventional | 2011-09-20 | Completed |
| Observational Cohort Study of Clinical Outcomes After Antiviral Therapy in Chronic Hepatitis C Patients [NCT04071353] | | 1,000 participants (Anticipated) | Observational | 2019-08-01 | Recruiting |
| Phase II Study of Low Dose Decitabine (5-Aza-Deoxycytidine) With Interferon Alfa-2b in Advanced Renal Cell Carcinoma [NCT00561912] | Phase 2 | 2 participants (Actual) | Interventional | 2007-10-31 | Terminated(stopped due to Low accrual.) |
| Pegylated Interferon Alpha-2b Plus Ribavirin Combination Treatment for Older Patients With Chronic Hepatitis C [NCT00956982] | | 1,251 participants (Anticipated) | Interventional | 2004-12-31 | Recruiting |
| A Phase 2 Randomized, Open Label, Multi-center, Therapeutic Trial of the Efficacy, Immunogenicity, and Safety of GI-5005; an Inactivated Recombinant Saccharomyces Cerevisiae Expressing a Hepatitis C Virus NS3-Core Fusion Protein, Combined With Pegylated I [NCT00606086] | Phase 2 | 140 participants (Actual) | Interventional | 2007-12-31 | Completed |
| Interferon Alpha Therapy for Cervical CIN I and HPV Infection [NCT06137950] | Phase 1 | 90 participants (Anticipated) | Interventional | 2023-11-07 | Recruiting |
| PEG-Interferon a-2b + Ribavirin for Treatment of Chronic Hepatitis C Infection in HIV-Infected Persons Not Previously Treated With Interferon [NCT00215891] | Phase 3 | 300 participants | Interventional | | Completed |
| An Open-label, Randomized, Active Controlled, Parallel Comparison Study of the Safety and Efficacy of REP 2139-Mg in Combination With Pegasys® and Viread® and REP 2165-Mg in Combination With Pegasys® and Viread® in Patients With HBeAg Negative Chronic Hep [NCT02565719] | Phase 2 | 40 participants (Actual) | Interventional | 2016-03-31 | Completed |
| The Treatment of Uveitic Cystoid Macular Edema With Topical Interferon Gamma [NCT00943982] | Phase 1 | 5 participants (Actual) | Interventional | 2009-07-17 | Completed |
| A Randomised, Open-label, Multi-centre Phase II Study of BAY43-9006 (Sorafenib) Versus Standard Treatment With Interferon Alpha-2a in Patients With Unresectable and/or Metastatic Renal Cell Carcinoma. [NCT00117637] | Phase 2 | 189 participants (Actual) | Interventional | 2005-06-30 | Completed |
| Prospective Anti-HCV Trial of Peg-Interferon and Ribavirin in Subjects of First Nations, Metis and Caucasian Ethnicity: PRAIRIE Study [NCT00957866] | Phase 4 | 160 participants (Anticipated) | Interventional | 2009-05-31 | Completed |
| Low Dose Treatment of Ribavirin in Combination With PEG-IFN Alfa-2b in CHC Patients With genotype1 High Viral Load and Low Body Weight [NCT00686777] | Phase 4 | 75 participants (Actual) | Interventional | 2008-01-31 | Completed |
| Neurobehavioral Deficits in HIV/HCV Infection Pre/Post Anti-HCV Therapy [NCT00747539] | | 330 participants (Actual) | Observational | 2008-07-31 | Completed |
| Protocol Title: A Phase II Open-labeled Study to Determine the Safety and Preliminary Efficacy of Interferon-gamma 1b (IFN-γ 1b) in Patients With Chronic Hepatitis B Who Are HBV DNA Positive [NCT00753467] | Phase 2 | 30 participants (Anticipated) | Interventional | 2008-09-30 | Not yet recruiting |
| A Randomized, Multinational, Double-Blind, Placebo-Controlled, Parallel-Group Design Pilot Study to Estimate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamic Effects of Teriflunomide for 24 Weeks When Added to Treatment With Interferon-beta [NCT00489489] | Phase 2 | 118 participants (Actual) | Interventional | 2007-05-31 | Completed |
| Phase II Study of the Anti-Ganglioside GD3 Mouse/Human Chimeric Antibody KW2871 Combined With High Dose Interferon-α2b in Patients With Metastatic Melanoma [NCT00679289] | Phase 2 | 36 participants (Actual) | Interventional | 2008-03-28 | Completed |
| The Effects of Interferon-gamma on Sepsis-induced Immunoparalysis, a Randomised Double-blind Placebo-controlled Pilot (Phase IIIb) Study [NCT01649921] | Phase 3 | 4 participants (Actual) | Interventional | 2012-11-30 | Completed |
| Study to Evaluate Efficacy and Safety of Glivec® in Combination With Vincristine and Dexamethasone in Patients With Lymphoid Blast Crisis CML or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in Relapse or Refractory [NCT00763763] | Phase 2 | 55 participants (Actual) | Interventional | 2004-12-31 | Completed |
| Optimization of Treatment for Patients With Chronic Hepatitis C Infected With HCV-genotype 2 or 3: 12 vs. 24 Weeks of Treatment Extension for Patients Without Rapid Virological Response [NCT00803309] | Phase 4 | 99 participants (Actual) | Interventional | 2008-11-30 | Terminated(stopped due to At the end of the planned recruitment period the expected number of subjects could not be included in the trial.) |
| The Observational Cohort Study on Long-term Clinical Outcomes of Antiviral Therapy in Patients With Chronic Hepatitis B and Cirrhosis [NCT04301908] | | 10,000 participants (Anticipated) | Observational | 2020-04-01 | Not yet recruiting |
| Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia [NCT02735707] | Phase 3 | 10,000 participants (Anticipated) | Interventional | 2016-04-11 | Recruiting |
| An Observational 20-year, Cross-sectional, Long-term Follow up of the Patient Cohort Enrolled in the Pivotal Study of Betaseron® (Interferon Beta-1b) in Relapsing-remitting Multiple Sclerosis [NCT01031459] | | 176 participants (Actual) | Observational | 2010-01-31 | Completed |
| An International, Multi Centre, Prospective, Observational Study of Safety, Tolerability and Adherence of Patients With Relapsing Remitting Multiple Sclerosis Administered Interferon Beta-1a (Rebif® New Formulation) in Real Life Settings [NCT01080027] | | 254 participants (Actual) | Observational | 2008-10-31 | Completed |
| Thalidomide-Dexamethasone vs Alpha-Interferon-Dexamethasone as Maintenance Therapy After Thalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin Combination for [NCT00633542] | Phase 3 | 103 participants (Actual) | Interventional | 2003-06-30 | Completed |
| Phase II Trial of Palliative Radiofrequency Ablation in Metastatic Renal Cell Carcinoma Patients With Small Primary Tumor [NCT00891475] | Phase 1/Phase 2 | 114 participants (Actual) | Interventional | 2008-05-31 | Completed |
| Antiviral Activity of Peg-IFN-Alpha-2A in Chronic HIV-1 Infection [NCT00594880] | Phase 2 | 23 participants (Actual) | Interventional | 2008-01-31 | Completed |
| A Multinational, Multicenter, Randomized, Parallel-Group Study Performed in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS) to Assess the Efficacy, Safety and Tolerability of Laquinimod Over Placebo in a Double-blind Design and of a Reference [NCT00605215] | Phase 3 | 1,331 participants (Actual) | Interventional | 2008-04-24 | Completed |
| Combination of Continuous Low Doses of Vinorelbine, Cyclophosphamide and Interferon Alpha 2b for Antiangiogenic/Antivascular Effect in Adult Advanced Neoplasm [NCT00908869] | Phase 1 | 30 participants (Actual) | Interventional | 2006-05-31 | Completed |
| HBsAg Loss Adding Pegylated Interferon Alfa-2a in HBeAg-negative Patients Treated With Nucleos(t)Ide Analogues. [NCT02743182] | | 119 participants (Actual) | Interventional | 2015-01-31 | Completed |
| Phase III Randomized Study of Adjuvant Biologic Therapy in Patients With Stages III/IV Head and Neck Squamous Cell Carcinoma [NCT00054561] | Phase 3 | 0 participants | Interventional | 2003-11-26 | Completed |
| An International Multicenter Double-blind Placebo-controlled Randomized Study to Compare the Efficacy, Safety and Tolerability of BCD-054 (JSC BIOCAD, Russia), 180 μg and 240 μg, Versus Avonex® (Biogen Idec Ltd., UK) in Patients With Relapsing-remitting M [NCT02744222] | Phase 2/Phase 3 | 399 participants (Actual) | Interventional | 2017-08-10 | Completed |
| Interleukin 12-Primed Activated T Cells For Patients With Metastatic Renal Cell Carcinoma Or Colorectal Carcinoma (Phase I) [NCT00016042] | Phase 1 | 0 participants | Interventional | 2001-01-31 | Active, not recruiting |
| An International Randomized Trial of Additional Treatments for COVID-19 in Hospitalized Patients Who Are All Receiving the Local Standard of Care Philippines [NCT05024006] | | 1,314 participants (Actual) | Interventional | 2020-04-23 | Completed |
| Efficacy and Safety of Peginterferon Beta-1a (CinnaGen) Versus CinnoVex® (CinnaGen) in Reducing the Annualized Relapse Rate in Participants With Relapsing Remitting Multiple Sclerosis: A Phase III, Randomized, Parallel, Noninferiority Study [NCT05242133] | Phase 3 | 168 participants (Actual) | Interventional | 2017-12-20 | Completed |
| Open Label, Randomized, Multicenter Phase II Study of a Combination of Torisel® (Temsirolimus) and Avastin® (Bevacizumab) Versus Sutent® (Sunitinib) and Versus a Combination of Avastin® (Bevacizumab) and Roféron® (Interferon Alpha-2a) in First-line Treatm [NCT00619268] | Phase 2 | 160 participants (Anticipated) | Interventional | 2008-02-29 | Completed |
| Thalidomide for Unresectable Hepatocellular Cancer With Optional Interferon Alpha-2a Upon Disease Progression [NCT00006006] | Phase 2 | 38 participants (Actual) | Interventional | 2000-08-31 | Completed |
| An Open-label, Multicenter, Phase IIIb Study Assessing the Long-term Efficacy and Safety of AOP2014 and Standard First Line Treatment (BAT) in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study [NCT02218047] | Phase 3 | 170 participants (Actual) | Interventional | 2014-11-30 | Completed |
| A Single-center, Single-blind, Randomized Controlled Clinical Study of Bowel Preparation Before Colonoscopy [NCT06091735] | | 444 participants (Anticipated) | Interventional | 2023-08-01 | Recruiting |
| Phase I/II Study of Autologous CD8+ and CD4+ Transgenic T Cells Expressing High Affinity MCPyV-Specific TCRs Combined With Avelumab and Class I MHC-Upregulation in Patients With Metastatic MCC Refractory to PD-1 Axis Blockade [NCT03747484] | Phase 1/Phase 2 | 16 participants (Anticipated) | Interventional | 2019-07-03 | Recruiting |
| An Open-label Multicenter Study Evaluating the Efficacy and Safety of 24 or 48 Weeks Pegylated Interferon Alfa-2a 40 kD (PEGASYS) Combination Therapy With Ribavirin (Copegus) in Patients With Chronic Hepatitis C Genotype 2 or 3 Infection Who Previously Ha [NCT00641654] | Phase 4 | 75 participants (Actual) | Interventional | 2007-01-31 | Terminated(stopped due to Recruitment problems in Denmark and Norway) |
| Evaluation of Natural Human Interferon Alpha Lozenges in the Treatment of Chronic Cough in Patients With Chronic Obstructive Pulmonary Disease (COPD) or Idiopathic Pulmonary Fibrosis (IPF) [NCT00690885] | Phase 2 | 1 participants (Actual) | Interventional | 2008-06-30 | Terminated(stopped due to Insufficient patient accrual) |
| A Phase II Trial Of Adjuvant Chemoradiation Following Pancreatic Resection For Adenocarcinomas Of The Pancreas Using 3-D Conformal Radiation With Cisplatin, 5FU, And Alpha-Interferon As Radiosensitizing Agents Followed By Gemcitabine [NCT00660270] | Phase 2 | 53 participants (Actual) | Interventional | 2002-05-31 | Completed |
| A Randomized Prospective Open-label Trial for Comparing Combination Therapy Peg-Interferon Alfa-2a/Adefovir Dipivoxil and Peg-Interferon Alfa-2a/Tenofovir Disoproxil Fumarate Versus no Treatment in HBeAg Negative Chronic Hepatitis B Patients With Low Vira [NCT00973219] | | 151 participants (Actual) | Interventional | 2009-09-30 | Completed |
| An Open Clinical Trial to Evaluate Ganovo（Danoprevir ） Combined With Ritonavir in the Treatment of SARS-CoV-2 Infection [NCT04291729] | Phase 4 | 11 participants (Actual) | Interventional | 2020-02-17 | Completed |
| A Phase 3 Randomized, Rater-Blinded Study Comparing Two Annual Cycles of Intravenous Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif®) in Treatment-Naïve Patients With Relapsing-Remitting Multiple Sclerosis [NCT00530348] | Phase 3 | 581 participants (Actual) | Interventional | 2007-08-31 | Completed |
| Inhibition of DNA Methylation by 1-hr Infusion of 5-aza-2'-Deoxycytidine (Decitabine) x 10 Days (M-F) With Escalating Doses of Sub-Q Pegylated (PEG) Interferon-alfa 2B (PEG-Intron): A Phase I Study With Molecular Correlates [NCT00886457] | Phase 1 | 3 participants (Actual) | Interventional | 2009-04-30 | Terminated(stopped due to low accrual) |
| Autologous Marrow Transplantation for Chronic Myelogenous Leukemia Using Stem Cells Obtained After In Vivo Cyclophosphamide/G-CSF Priming [NCT00005984] | Phase 2 | 22 participants (Actual) | Interventional | 2000-08-31 | Terminated(stopped due to Study terminated as principal investigator [PI] left the university.) |
| A Non-interventional Study Evaluating Injectable Treatments (Ofatumumab, Glatiramer Acetate and Interferon β1) in Patients With Relapsing Multiple Sclerosis [AIOLOS] [NCT05344469] | | 800 participants (Anticipated) | Observational | 2022-05-10 | Recruiting |
| Phase II Study to Evaluate the Efficacy of Recombinant Interferon-Alpha in the Treatment of Recurrent Unresectable Meningiomas and Malignant Meningiomas [NCT00002965] | Phase 2 | 16 participants (Actual) | Interventional | 1997-01-31 | Completed |
| Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs [NCT04278404] | | 5,000 participants (Anticipated) | Observational | 2020-03-05 | Recruiting |
| Pregnancy Outcomes in Women Exposed to Diroximel Fumarate [NCT05688436] | | 1,178 participants (Anticipated) | Observational [Patient Registry] | 2021-09-24 | Recruiting |
| Betaferon® Injection Management: Non-interventional Study on Personal Digital Assistant (PDA)Supported Effects on Adherence to a Long-term Injection Therapy (BETAPATH) [NCT00902135] | | 702 participants (Actual) | Observational | 2009-05-31 | Completed |
| A 12-month Double-blind, Randomized, Multicenter, Active-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5 mg and 1.25 mg Fingolimod (FTY720) Administered Orally Once Daily Versus Interferon ß-1a (Avonex) Administered im Once Weekl [NCT00340834] | Phase 3 | 1,292 participants (Actual) | Interventional | 2006-05-31 | Completed |
| Prospective Multicenter, Non-interventional Study to Evaluate the Impact of the Introduction of Interferon Beta-1 b Treatment on Daily Life Activities in Patients at High Risk of Developing Multiple Sclerosis After a First Clinical Demyelinating Event or [NCT00928967] | | 67 participants (Actual) | Observational | 2007-05-31 | Completed |
| A Phase II Study of Chemoimmunotherapy for Patients With Potentially Platinum Sensitive Müllerian (Epithelial Ovarian, Peritoneal, or Fallopian Tube) Carcinomas [NCT00501644] | Phase 2 | 59 participants (Actual) | Interventional | 2003-01-31 | Completed |
| A Phase 3, Randomized, Rater- and Dose-Blinded Study Comparing Two Annual Cycles of Intravenous Low- and High-Dose Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta 1a (Rebif®) in Patients With Relapsing Remitting Multiple Sclerosis Who Have [NCT00548405] | Phase 3 | 840 participants (Actual) | Interventional | 2007-10-31 | Completed |
| Study Evaluating Betaferons® Safety and Tolerability In Pediatric Patients With Multiple Sclerosis [NCT00963833] | | 68 participants (Actual) | Observational | 2009-12-17 | Completed |
| The Individualized Management With Pegasys and Ribavirin Offering Viral Eradication (IMPROVE) Trial [NCT00483938] | Phase 3 | 236 participants (Actual) | Interventional | 2007-06-30 | Completed |
| Open Label Study to Evaluate the Effect, Safety and Tolerability of 250µg (8 MIU) Interferon Beta 1b (Betaferon) Given Subcutaneously Every Other Day (for 24 Weeks) in Patients of Chinese Origin With Multiple Sclerosis [NCT00370071] | Phase 3 | 39 participants (Actual) | Interventional | 2006-11-30 | Completed |
| A Phase 2 Rollover Protocol of Telaprevir (VX-950) in Combination With Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Subjects Enrolled in the Control Group (Group A) of Study VX06-950-106, VX05-950-104 and VX05-950-104EU Who Did Not Achieve [NCT00535847] | Phase 2 | 117 participants (Actual) | Interventional | 2007-10-31 | Completed |
| A Randomized Phase II/III Trial of SCH 54031 PEG12000 Interferon Alfa-2b (PEG Intron) vs. INTRON®A as Adjuvant Therapy for Melanoma [NCT03552549] | Phase 2/Phase 3 | 126 participants (Actual) | Interventional | 1998-08-05 | Terminated(stopped due to This study was closed to enrollment prematurely due to sub-optimal accrual.) |
| Combination Therapy Using Mycophenolate Mofetil (CellCept) and Human Interferon beta1a (Rebif) in Early Treatment of Multiple Sclerosis [NCT00618527] | Early Phase 1 | 31 participants (Actual) | Interventional | 2006-08-31 | Completed |
| Inhibition of DNA Methylation by 1-Hr Infusion of 5-aza-2'-Deoxycitidine (Decitabine) x 10 Days (M-F) With Escalating Doses of Sub-Q Pegylated (PEG) Interferon-alpha 2B (PEG-Intron): A Phase I Study With Molecular Correlates [NCT00701298] | Phase 1 | 30 participants (Actual) | Interventional | 2009-04-30 | Terminated |
| A Multicenter, Open-Label, Immunogenicity and Safety Study of Avonex® (Interferon Beta-1a) 30 mcg Administered Subcutaneously to Subjects With Relapsing Multiple Sclerosis [NCT00784836] | Phase 3 | 3 participants (Actual) | Interventional | 2008-10-31 | Terminated(stopped due to Terminated early by Sponsor for business reasons unrelated to safety.) |
| A Multi-center, Randomized, Parallel-group, Rater-blinded Study Comparing the Effectiveness and Safety of Teriflunomide and Interferon Beta-1a in Patients With Relapsing Multiple Sclerosis Plus a Long Term Extension Period [NCT00883337] | Phase 3 | 324 participants (Actual) | Interventional | 2009-04-30 | Completed |
| Treatment of Acute Hepatitis C Virus in HIV Co-Infection [NCT00845676] | Phase 4 | 21 participants (Actual) | Interventional | 2008-03-31 | Completed |
| An Evaluation of Two Dose Routes of HDV-Interferon Administered With Ribavarin in the Treatment of Chronic Hepatitis C Nonresponders and Naive Hepatitis C Patients [NCT00703872] | Phase 2 | 50 participants (Anticipated) | Interventional | 2008-05-31 | Active, not recruiting |
| A Phase II Randomized Placebo-controlled Study to Evaluate the Safety and Efficacy of MK-7009 Administered Concomitantly With Pegylated-Interferon and Ribavirin for 28 Days in Japanese Treatment-Experienced Patients With Chronic Hepatitis C Infection [NCT00880763] | Phase 2 | 90 participants (Actual) | Interventional | 2009-04-20 | Completed |
| Pegylated Interferon Alfa-2a for Dialysis Patients With Acute Hepatitis C [NCT00917358] | Phase 4 | 42 participants (Actual) | Interventional | 2005-07-31 | Completed |
| Phase 2 Study of PEG-Intron in Hereditary Hemorrhagic Telangiectasia [NCT00588146] | Phase 2 | 10 participants (Actual) | Interventional | 2007-01-31 | Terminated(stopped due to Schering-Plough discontinued supplying study drug.) |
| Pegetron® Redipen™ Prospective Optimal Weight-based Dosing Response Program [NCT00724893] | | 2,430 participants (Actual) | Observational | 2005-08-31 | Completed |
| Phase II Study of Recombinant Interferon Alpha and Etoposide in Patients With Relapsed Osteosarcoma [NCT00504140] | Phase 2 | 30 participants (Actual) | Interventional | 1996-11-30 | Completed |
| )A Study to Evaluate the Erythropoietic Response in HCV/HIV Co-Infected Patients Receiving Combination Ribavirin/Interferon Therapy [NCT00315432] | Phase 2 | 91 participants (Actual) | Interventional | 2000-09-30 | Completed |
| An Open-label, Multicenter Protocol Providing Pegylated-interferon Alfa-2a (PEGASYS®) as Monotherapy or in Combination With Ribavirin (COPEGUS®) for Patients With Chronic Hepatitis C Who Have Participated in Previous Roche or Roche Partner Protocols [NCT00800735] | Phase 3 | 30 participants (Actual) | Interventional | 2009-04-30 | Completed |
| a Multi-sites, Randomized, Parallel, Placebo-Controlled Clinical, Pilot Study to Evaluated the Efficacy and Safety of Recombinant Human Interferon Alpha-2b Gel (Yallaferon®) in HPV Infection [NCT02593968] | Phase 2 | 100 participants (Anticipated) | Interventional | 2015-09-30 | Recruiting |
| International, Multicenter, Phase IIIb Study of Subcutaneous Every-other-day Treatment of Patients With Relapsing Multiple Sclerosis With (Phase A): Double-blind Betaseron/Betaferon 250µg or 500µg or Open-label Betaseron/Betaferon 250µg and (Phase B): Ope [NCT00459667] | Phase 3 | 1,420 participants (Actual) | Interventional | 2007-05-31 | Completed |
| An Open-Label, Multicenter Study to Evaluate the Safe and Effective Use of the Single-Use Autoinjector With an Avonex® Prefilled Syringe in Multiple Sclerosis Subjects [NCT00828204] | Phase 3 | 95 participants (Actual) | Interventional | 2009-01-31 | Completed |
| A Study of Adjuvant Cytokine Therapy in Pulmonary Mycobacterium Avium Complex and Other Pulmonary Nontuberculous Mycobacterial Infections [NCT00111397] | Phase 1 | 2 participants (Actual) | Interventional | 2005-05-13 | Completed |
| Cost-effectiveness of Quantiferon Gold in VITRO Test of T-lymphocytic Response for Detection of Latent Tuberculosis in At-risk Healthcare Workers [NCT00797836] | Phase 4 | 1,024 participants (Actual) | Interventional | 2008-11-30 | Completed |
| An Open Label Study of the Effect of First Line Treatment With Avastin (Bevacizumab) in Combination With Low-dose Interferon on Progression-free Survival in Patients With Metastatic Clear Cell Renal Cell Carcinoma. [NCT00796757] | Phase 2 | 146 participants (Actual) | Interventional | 2008-12-31 | Completed |
| Adoptive T Cell Therapy in Patients With Recurrent Ovarian Cancer [NCT04072263] | Phase 1/Phase 2 | 12 participants (Anticipated) | Interventional | 2018-08-01 | Recruiting |
| Efficacy and Safety of High-dose Treatment With the Immunomodulator Interferon-α-2b (Intron A®) for the Adjuvant Treatment of Malignant Melanoma. [NCT00749684] | | 138 participants (Actual) | Observational | 1996-12-31 | Completed |
| Treatment of Chronic Hepatitis C in Children With Intron Vial or Pen and Rebetol According to German Law (§ 67 Abs 6 AMG) [NCT00727077] | | 3 participants (Actual) | Observational | 2006-06-30 | Terminated(stopped due to Study halted due to low recruitment. The 3 participants at time of termination transferred into study P04538 (NCT00727077). See NCT00727077 for details/results.) |
| Brimonidine Tartrate for the Treatment of Injection Related Erythema Associated With Sub-cutaneous Administration of Peginterferon Beta-1a (BRITE) [NCT02568111] | Phase 4 | 0 participants (Actual) | Interventional | 2016-02-29 | Withdrawn |
| A Randomised, Double-blind Study to Evaluate the Efficacy and Safety of Avastin Plus Roferon Compared With Placebo Plus Roferon on Overall Survival and Tumor Assessment in Nephrectomised Patients With Metastatic Clear Cell Renal Cell Carcinoma [NCT00738530] | Phase 3 | 649 participants (Actual) | Interventional | 2004-06-30 | Completed |
| A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Low-Dose Human Interferon-alpha by the Oral Mucosal Route During the 6-Month Follow-up Period of Standard Combination Therapy for Hepatitis C Virus Infection [NCT00695019] | Phase 2 | 169 participants (Actual) | Interventional | 2009-06-30 | Completed |
| Guidelines to the Intron A® Health Management Program II: A Nursing Support Program for Patients With High-Risk Melanoma Receiving High Dose Intron A Therapy [NCT00723710] | | 299 participants (Actual) | Observational | 2006-04-30 | Completed |
| A Randomized, Open-label, Multi-center Phase II Study to Compare Bevacizumab Plus RAD001 Versus Interferon Alfa-2a Plus Bevacizumab for the First-line Treatment of Patients With Metastatic Clear Cell Carcinoma of the Kidney [NCT00719264] | Phase 2 | 365 participants (Actual) | Interventional | 2008-11-12 | Completed |
| An Open, Randomized, Multicentre Trial to Evaluate Efficacy and Safety of a 24-week Course of PEG-Interferon Alpha-2b Versus a 12-week Course of PEG-Interferon Alpha-2b Alone or Plus Ribavirin in Patients With Acute Hepatitis C [NCT00686517] | Phase 3 | 130 participants (Actual) | Interventional | 2003-12-31 | Completed |
| Modulation of Plasmacytoid Dendritic Cell Function in Multiple Sclerosis [NCT00468182] | | 24 participants (Actual) | Observational | 2007-04-30 | Completed |
| A Phase II Protocol in Borderline Resectable Pancreatic Cancer Using Gemcitabine/Docetaxel Chemotherapy and An Oxaliplatin-Based Chemoradiation. [NCT00761241] | Phase 2 | 40 participants (Anticipated) | Interventional | 2008-09-30 | Completed |
| Evaluation of Emotional Disorders During Treatment by Interferon Beta in Relapsing-remitting Multiple Sclerosis Patients [NCT01201343] | Phase 4 | 79 participants (Actual) | Interventional | 2005-01-31 | Completed |
| A Phase II Trial of Celecoxib Plus Interferon Alpha in Metastatic Renal Cell Carcinoma Patients With 3+ COX-2 Tumor Immunostaining [NCT01158534] | Phase 2 | 17 participants (Actual) | Interventional | 2006-03-31 | Completed |
| Phase II Study of Low-Dose Interferon Alfa 2B (Schering Plough) Plus Thalidomide (Celgene) for Patients With Resected High-Risk Soft Tissue Sarcoma [NCT00026416] | Phase 2 | 0 participants | Interventional | 2001-10-31 | Active, not recruiting |
| An Open-label, Dose-ranging, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Lonafarnib With Ritonavir-Boosting +/- Peginterferon Alfa-2a in Patients Chronically Infected With Delta Hepatitis (HDV) (LOWR-2) [NCT02430194] | Phase 2 | 55 participants (Actual) | Interventional | 2014-12-31 | Completed |
| A Parallel Phase I/II Study of Low Dose Decitabine (5-Aza-Deoxycytidine) With Peginterferon Alfa-2b in Advanced Melanoma [NCT00791271] | Phase 1 | 17 participants (Actual) | Interventional | 2008-09-02 | Terminated |
| Open-Label, Single Arm Evaluation of BMS-790052 (Daclatasvir) in Combination With Peg-Interferon Alfa-2a and Ribavirin in Black-African Americans, Latinos and White-Caucasians With Chronic Hepatitis C Genotype 1 Infection [NCT01389323] | Phase 3 | 448 participants (Actual) | Interventional | 2011-09-30 | Completed |
| An Open, Prospective/Retrospective, Randomized Controlled Cohort Study to Compare the Efficacy of Two Therapeutic Schemes(Abidol Hydrochloride,Abidol Hydrochloride Combined With Interferon Atomization)in the Treatment of 2019-nCoV Pneumonia. [NCT04254874] | Phase 4 | 100 participants (Anticipated) | Interventional | 2020-02-01 | Recruiting |
| A Randomized, Double-Blind, Double-Dummy, Parallel-Group Study To Evaluate the Efficacy and Safety of Ocrelizumab in Comparison to Interferon Beta-1a (Rebif®) in Patients With Relapsing Multiple Sclerosis [NCT01247324] | Phase 3 | 821 participants (Actual) | Interventional | 2011-08-31 | Completed |
| Phase IV, Multicenter, Open Label, Randomized Study of Rebif® 44mcg Administered Three Times Per Week by Subcutaneous Injection Compared With no Treatment in the Therapy of Relapsing Multiple Sclerosis After Mitoxantrone [NCT01142466] | Phase 4 | 30 participants (Actual) | Interventional | 2005-12-31 | Completed |
| A Phase 3, Open Label Study of Safety and Efficacy With BMS-790052 Plus Peg-Interferon Alfa 2a and Ribavirin in Previously Untreated HCV Patients Coinfected With Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) [NCT01471574] | Phase 3 | 549 participants (Actual) | Interventional | 2011-12-31 | Completed |
| A Randomized, Open Labeled, Active-Controlled Trial of 24-Week Versus 48-Week Courses of Peg-Interferon Alpha Plus Ribavirin for Genotype-1 Infected Chronic Hepatitis C Patients [NCT00629967] | Phase 4 | 200 participants (Actual) | Interventional | 2005-04-30 | Completed |
| Tailored Treatment of Hepatitis C Genotype 1 [NCT00910975] | Phase 4 | 100 participants (Actual) | Interventional | 2007-11-30 | Completed |
| Early Response to Interferon Combined Short-Term Nucleoside Analogue Therapy in HBeAg(+) Chronic Hepatitis B [NCT00860626] | | 50 participants (Anticipated) | Interventional | 2008-01-31 | Recruiting |
| An Exploratory Study of Adjuvant Therapy of Pegylated Interferon-Alfa 2b Plus Melanoma Peptide Vaccine in Patients With Resected Stage II and III (N1a, N2a) Melanoma [NCT00861406] | Phase 1 | 38 participants (Actual) | Interventional | 2009-03-10 | Completed |
| Targeted Oncolytic Virotherapy and Natural History Study of KSHV-Associated Multicentric Castleman's Disease With Laboratory and Clinical Correlates of Disease Activity [NCT00092222] | Phase 2 | 75 participants (Actual) | Interventional | 2004-10-28 | Active, not recruiting |
| Safety, Pharmacokinetics and Antiviral Effect of BI 201335 NA in HCV-1 Infected Patients Treated for 28 Days for Treatment naïve and Experienced Patients Treated in Combination With Peg Interferon Alfa-2a and Ribavirin [NCT00947349] | Phase 2 | 22 participants (Actual) | Interventional | 2009-07-31 | Completed |
| Characteristic Study on Chinese Patients With Multiple Sclerosis [NCT00818103] | | 600 participants (Anticipated) | Interventional | 2006-01-31 | Recruiting |
| A Phase II, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of MK7009 Administered Concomitantly With Pegylated-Interferon and Ribavirin for 28 Days in Treatment-Naive Patients With Chronic Hepatitis C Infection [NCT00704184] | Phase 2 | 95 participants (Actual) | Interventional | 2008-07-25 | Completed |
| Phase 3b, Randomized, Open-Label Study Of Bevacizumab + Temsirolimus Vs. Bevacizumab + Interferon-Alfa As First-Line Treatment In Subjects With Advanced Renal Cell Carcinoma [NCT00631371] | Phase 3 | 791 participants (Actual) | Interventional | 2008-04-30 | Completed |
| PILOT-high Throughput-protein Profiling Analysis of Sera Collected From E1694 Patients Undergoing HDI (Arm B) [NCT00897520] | | 40 participants (Actual) | Observational | 2008-01-14 | Completed |
| Analysis of Gene Expression of PBMC in the Hepatitis C Virus Genotype 1b-infected Patients During Peg-interferon-α Plus Ribavirin Combination Therapy [NCT00680173] | Phase 4 | 30 participants (Actual) | Interventional | 2006-08-31 | Completed |
| Pregnancy Outcomes in Multiple Sclerosis Populations Exposed and Unexposed to Interferon β - a Register-based Study in the Nordic Countries [NCT02749396] | | 2,089 participants (Actual) | Observational | 2016-05-02 | Completed |
| A Phase I Study of 5-azacytidine (Vidaza) With Interferon α2b in Metastatic Melanoma Patients [NCT00398450] | Phase 1 | 12 participants (Anticipated) | Interventional | 2006-02-28 | Completed |
| Role of Heme Oxygenase in the Pathogenesis od Hepatocellular Injury in Chronic HCV Infection [NCT00842205] | | 150 participants (Anticipated) | Interventional | 2007-01-31 | Recruiting |
| A Phase 2 Study of VX-950 in Combination With Peginterferon Alfa-2a (Pegasys®), With and Without Ribavirin (Copegus®) in Subjects With Hepatitis C [NCT00372385] | Phase 2 | 334 participants (Actual) | Interventional | 2006-08-31 | Completed |
| Randomized Phase II Trial of Dendritic Cell-Based Idiotype Vaccination With Adjuvant Cytokines for Plateau Phase and Post-Transplant Multiple Myeloma [NCT00616720] | Phase 2 | 15 participants (Anticipated) | Interventional | 2001-08-31 | Completed |
| A Randomized Phase II Trial of Interferon + GM-CSF Versus K562/GM-CSF Vaccination in CML Patients Achieving a Complete Cytogenetic Response to Frontline Tyrosine Kinase Inhibitor Therapy [NCT00363649] | Phase 2 | 36 participants (Actual) | Interventional | 2006-09-30 | Completed |
| An Open-Label, Randomized, Comparative Study With PegIntron vs. Adefovir in the Treatment of Chronic Hepatitis B (CHB) e Antigen Positive Patients in Taiwan [NCT00371761] | Phase 3 | 25 participants (Actual) | Interventional | 2006-09-30 | Completed |
| Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma [NCT01758458] | Phase 1/Phase 2 | 4 participants (Actual) | Interventional | 2013-02-28 | Terminated(stopped due to A Phase I/II study (NCT01758458) is now recruiting) |
| Phase II/III Study of Recombinant Anti-tumor and Anti-Virus Protein for Injection Compared With Placebo in Metastatic Colorectal Cancer After Failure of Second-Line and More Than Second-line Treatment [NCT01386242] | Phase 2 | 108 participants (Actual) | Interventional | 2011-05-31 | Completed |
| A Phase II, Randomized, Open-label, Multicenter, Study Evaluating the Efficacy of Sorafenib Alone and Sorafenib in Combination With Low Dose Interferon Alpha-2a as Second-line Treatment of Sunitinib Failure in Patients With Metastatic Renal Cell Carcinoma [NCT00678288] | Phase 2 | 16 participants (Actual) | Interventional | 2008-04-30 | Terminated |
| Phase II Study of a Multi-Antigen Therapeutic Vaccine in Patients With Metastatic Melanoma [NCT00613509] | Phase 2 | 23 participants (Actual) | Interventional | 2008-06-30 | Terminated(stopped due to No safety concerns, the study was terminated due to slow enrollment. All enrolled patients were followed per protocol.) |
| Betaferon Treatment and Exercise Data Gathering IN Early MS [NCT00882453] | | 1,739 participants (Actual) | Observational | 2006-08-31 | Completed |
| Phase 2 Study of Interferon Alfa-2b and Lovastatin Combination Therapy for Patients With High-risk Resected or Unresectable Malignant Melanoma [NCT00963664] | Phase 2 | 250 participants (Anticipated) | Interventional | 2009-12-31 | Withdrawn(stopped due to Modifications will be necessary before full IRB approval will be secured.) |
| Randomized Phase 1/2 Evaluation of Neoadjuvant Administration of a Chemokine-Modulatory Regimen in Patients With Recurrent Resectable Colorectal Cancer [NCT01545141] | Phase 1/Phase 2 | 15 participants (Actual) | Interventional | 2012-10-31 | Terminated |
| Phase I/II Prospective, Open Label and Multicentric Clinical Trial to Determine the Recommended Dose (Phase I) and Efficacy of Pazopanib in Combination With Interferon Alfa 2-A (Phase II), in Patients With Advanced Renal Cell Carcinoma [NCT01513187] | Phase 1/Phase 2 | 53 participants (Actual) | Interventional | 2011-07-11 | Completed |
| [NCT01404117] | Phase 2 | 0 participants (Actual) | Interventional | 2012-03-31 | Withdrawn(stopped due to Study is being redesigned) |
| IPI-Biotherapy for Patients With Metastatic Melanoma Previously Treated With Cytotoxic Drugs [NCT01409187] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2011-10-31 | Withdrawn |
| Prospective Open Controlled Non-interventional Study of the Use of the Drug Ingaron (Interferon Gamma Human Recombinant, NPP Farmaklon LLC, Russia) in Volunteers for the Prevention of Coronavirus Infection COVID-19 [NCT05386446] | | 100 participants (Actual) | Observational | 2020-04-23 | Completed |
| Double-blind, Randomized, Parallel Group, Multicenter Study of the Safety and Tolerability of Betaseron 500 Mcg Subcutaneously Every Other Day and Betaseron 250 Mcg Subcutaneously Every Other Day for at Least 12 Weeks in Patients With RRMS [NCT00893217] | Phase 2 | 71 participants (Actual) | Interventional | 2002-11-30 | Completed |
| Augmenting Response to Entecavir Using a Temporary Peginterferon Alpha-2a add-on Strategy for the Treatment of HBeAg-positive Chronic Hepatitis B [NCT00877760] | Phase 4 | 184 participants (Actual) | Interventional | 2009-08-31 | Completed |
| Dynamic Contrast Enhanced MRI (DCE-MRI) Assessment of the Vascular Changes Induced With Bevacizumab Alone and in Combination With Interferon-α in Patients With Advanced Renal Cell Carcinoma [NCT00873236] | Phase 2 | 30 participants (Anticipated) | Interventional | 2008-04-30 | Recruiting |
| A Phase II Randomized, Multicenter, Open-label Study of TG4040 (MVA-HCV) in Combination With Pegylated Interferon Alfa-2a and Ribavirin Versus Pegylated Interferon Alfa-2a and Ribavirin in Treatment-naïve Patients With Chronic Genotype 1 Hepatitis C. [NCT01055821] | Phase 2 | 140 participants (Actual) | Interventional | 2010-05-31 | Completed |
| Peginterferon Alfa-2a Plus Ribavirin Combination Treatment in Chronic Hepatitis C Post-Renal Transplant Patients [NCT00881582] | Phase 4 | 32 participants (Actual) | Interventional | 2009-01-31 | Completed |
| Phase 3 Study of Adjuvant Chemoradiotherapy of Advanced Resectable Rectal Cancer Comparing Modulation of 5-FU With Folinic Acid or With Interferon-alpha [NCT01060501] | Phase 3 | 796 participants (Actual) | Interventional | 1992-07-31 | Completed |
| A Phase II Trial of Chemosensitization With Paclitaxel, 13-cis Retinoic Acid and Interferon Alpha-2b in Advanced Uterine Cervical Carcinoma [NCT00138151] | Phase 2 | 33 participants (Actual) | Interventional | 2001-03-31 | Terminated(stopped due to Slow accrual and lack of study drug) |
| Hepatitis C Virus Dynamic and Immune Activation in HIV-1 Coinfected Patients Treated With Pegylated Interferon Alfa-2a and Ribavirin [NCT00909129] | | 25 participants (Actual) | Interventional | | Completed |
| A Multicenter Study of the Safety and Anti-Fibrotic Efficacy of Interferon-Gamma 1b (Actimmune) in Patients With Severe Lever Fibrosis or Compensated Cirrhosis Due to Hepatitis C. [NCT00043303] | Phase 2 | 502 participants (Actual) | Interventional | 2001-09-30 | Completed |
| An Open Controlled Study of the Efficacy and Safety of Ingaron (Interferon-gamma Human Recombinant) in the Treatment of Chronic Prostatitis [NCT05378646] | Phase 3 | 30 participants (Actual) | Interventional | 2009-01-29 | Completed |
| Adjuvant Therapy for Patients With Primary Uveal Melanoma With Genetic Imbalance [NCT01100528] | Phase 2 | 38 participants (Actual) | Interventional | 2009-11-11 | Completed |
| Evaluation of Natural Human Interferon Alpha Lozenges in the Prevention of Winter Colds and Flu in Perth, Western Australia [NCT00895947] | Phase 2 | 200 participants (Actual) | Interventional | 2009-04-30 | Completed |
| A Blinded, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-333 Alone and in Combination With Pegylated Interferon (pegIFN) and Ribavirin (RBV) in Subjects With Ge [NCT00851890] | Phase 2 | 30 participants (Actual) | Interventional | 2009-03-31 | Completed |
| An Investigation Into Beneficial Effects of Interferon Beta 1a, Compared to The Base Therapeutic Regiment in Moderate to Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial [NCT04350671] | Phase 4 | 40 participants (Anticipated) | Interventional | 2020-04-15 | Enrolling by invitation |
| A Phase 1 Study to Evaluate the Pharmacokinetic and Pharmacodynamic Profile, Safety, and Tolerability of Escalating Single Dose Recombinant Human Serum Albumin/Interferon alpha2b Fusion Protein in Healthy Chinese Volunteers [NCT02781753] | Phase 1 | 34 participants (Actual) | Interventional | 2016-04-07 | Completed |
| Human Recombinant Interferon Gamma-1b for the Prevention of Hospital-acquired Pneumonia in Critically Ill Patients: a Double-blind, International, Phase 2, Randomized, Placebo-controlled Trial - the PREV-HAP Study [NCT04793568] | Phase 2 | 109 participants (Actual) | Interventional | 2021-03-29 | Active, not recruiting |
| Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-986202 in Healthy Subjects and to Evaluate the Safety, Tolerability, Pharmacokinetic [NCT02763969] | Phase 1 | 357 participants (Actual) | Interventional | 2016-05-18 | Completed |
| An Open-label, Randomized, Multicenter, Active-controlled, Dose-ranging Study to Evaluate the Safety and Efficacy of Albinterferon Alfa 2b Administered Every 4 Weeks Plus Ribavirin in Interferon Alfa-naïve Patients With Genotype 2/3 Chronic Hepatitis C [NCT00759200] | Phase 2 | 525 participants (Anticipated) | Interventional | 2008-10-31 | Completed |
| Efficacy, Safety and Tolerability of Atorvastatin 40 mg in Patients With Relapsing-remitting Multiple Sclerosis Treated With Interferon-beta-1b.SWiss Atorvastatin and Interferon-Beta 1b Trial In Multiple Sclerosis. [NCT00942591] | Phase 2 | 77 participants (Actual) | Interventional | 2005-05-31 | Completed |
| Effect of Interferon-gamma 1-b on Innate Immune Cells [NCT02609932] | Phase 1 | 20 participants (Actual) | Interventional | 2016-07-31 | Completed |
| US PROmyBETAapp2.0: Ascertaining Medication Usage and Patient-reported Outcomes (PROs) Via the myBETAapp™ in Patients With Multiple Sclerosis Treated With BETASERON® Using BETACONNECT™ Autoinjector [NCT04356339] | | 100 participants (Actual) | Observational | 2020-11-24 | Completed |
| An Open-Label Safety Extension Study of AVONEX® (Interferon Beta-1a) Treatment in Subjects Who Completed Biogen Studies C95-812, C96-823, or C97-830 [NCT00915460] | Phase 4 | 408 participants (Actual) | Interventional | 1999-09-30 | Completed |
| A Randomized Study to Evaluate the Safety and Efficacy of IDX719 in Combinations With Simeprevir and/or TMC647055/Ritonavir With or Without Ribavirin for 12 Weeks in Subjects With Chronic Hepatitis C Infection [NCT01852604] | Phase 2 | 143 participants (Actual) | Interventional | 2013-03-31 | Completed |
| Carcinoid Tumors After Failure of Somatostatin Analogs: a Randomized Phase III of Octreotide Lutate Peptid Receptor Radionuclide Therapy (PRRT) Versus Interferon α-2b [NCT01860742] | Phase 3 | 0 participants (Actual) | Interventional | 2014-12-31 | Withdrawn |
| A Phase 1 Study to Evaluate the Pharmacokinetic and Pharmacodynamic Profile, Safety, and Tolerability of Escalating Single Dose Recombinant Human Serum Albumin/Interferon alpha2a Fusion Protein in Healthy Volunteers [NCT01901198] | Phase 1 | 34 participants (Actual) | Interventional | 2013-04-30 | Completed |
| Profile of Mother-caregivers of Children With Duchenne Muscular Dystrophy [NCT01921374] | | 60 participants (Actual) | Interventional | 2013-08-31 | Completed |
| The Efficiency of Postoperative Interferon-alpha(IFNa) Treatment in p48 Positive Patients With Hepatocellular Carcinoma [NCT00838968] | | 0 participants (Actual) | Interventional | 2008-01-31 | Withdrawn(stopped due to we have found another marker (microRNA26) which is more sensitive to evaluate the effect of postoperative IFNa treatment in patients with HCC) |
| A Randomized Phase 2a, Multicenter, Open-label Study Evaluating ABI-H0731-Containing Regimens in Patients With Chronic Hepatitis B [NCT04781647] | Phase 2 | 54 participants (Actual) | Interventional | 2021-02-18 | Terminated(stopped due to Study ABI-H0731-203 was terminated early by the study Sponsor for strategic reasons to prioritize research and development efforts on finite and curative HBV therapies.) |
| A Pilot Phase II Study of Immunotherapy for the Treatment of AML, ALL, BP CML, and MDS Relapsed After Allogeneic Transplantation [NCT00548847] | Phase 2 | 15 participants (Actual) | Interventional | 2007-01-31 | Completed |
| Phase II, Multicenter, Randomized, Parallel-Group, Partially Blinded, Placebo and Avonex Controlled Dose Finding Study to Evaluate the Efficacy As Measured by Brain MRI Lesions, and Safety of 2 Dose Regimens of Ocrelizumab in Patients With RRMS [NCT00676715] | Phase 2 | 220 participants (Actual) | Interventional | 2008-07-17 | Active, not recruiting |
| A Randomized, Multicenter, Open Label Study Evaluating the Efficacy and Safety of Tailored Regimens With Peginterferon Alfa-2a Plus Ribavirin According Viral Kinetics for Genotype 1 Chronic Hepatitis C Patients [NCT01937728] | Phase 4 | 542 participants (Actual) | Interventional | 2010-03-31 | Completed |
| A Randomized, Phase I/II Clinical Trial Evaluating the Safety, Reactogenicity, and Immunogenicity of Licensed Trivalent Influenza Vaccine Administered With Recombinant Interferon Alpha Among Patients With Chronic Lymphocytic Leukemia [NCT00962715] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2011-04-30 | Withdrawn |
| Phase II Study of Weekly Administered High-Dose Pegylated Interferon Alfa-2B (PEGIntron) in Advanced Stage Low Grade Non-Hodgkin's Lymphoma [NCT00006039] | Phase 2 | 0 participants | Interventional | 1999-12-31 | Completed |
| PEG-Intron Observation After Regional Lymph Node Dissection in AJCC Stage III (TxN1-2MO) Melanoma Patients: a Randomized Phase III Trial [NCT00006249] | Phase 3 | 1,258 participants (Actual) | Interventional | 2000-06-30 | Active, not recruiting |
| Autologous Transplantation for Chronic Myelogenous Leukemia Using Retrovirally Marked Peripheral Blood Progenitor Cells Obtained After In Vivo Cyclophosphamide/G-CSF Priming [NCT00005986] | Phase 2 | 0 participants | Interventional | 2000-08-31 | Terminated(stopped due to Principal investigator left the university.) |
| Phase II Trial of SU5416 and Interferon Alfa 2B in Unresectable or Metastatic Renal Cell Carcinoma [NCT00006384] | Phase 2 | 0 participants | Interventional | 2000-11-30 | Completed |
| A Phase III Study of STI571 Versus Interferon-a (IFN-a) Combined With Cytarabine (Ara-C) in Patients With Newly Diagnosed Previously Untreated Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) [NCT00006343] | Phase 3 | 0 participants | Interventional | 2000-06-30 | Completed |
| Phase II Evaluation of Immunization With an HLA-A2 Multi-Epitope Peptide Vaccine Containing MART-1 (NSC #672643), gp100 (NSC #683472), and Tyrosinase (NSC #699048) Peptides Alone or in Combination With GM-CSF, IFN Alpha-2b, or GM-CSF + IFN Alpha-2b in Pat [NCT00006385] | Phase 2 | 0 participants | Interventional | 2000-09-30 | Completed |
| Phase 2 Study Of High Dose Chemotherapy Followed By Autologous Hematopoietic Stem Cell Support In Patients With Multiple Myeloma And Primary Light Chain Amyloidosis [NCT00007995] | Phase 2 | 75 participants (Anticipated) | Interventional | 1999-07-31 | Completed |
| High-Dose Chemotherapy Followed By Autologous Hematopoietic Stem Cell Support And One Of Two Regimens Aimed At Modifying Immune Reconstitution In Women With High Risk Stage 2 And Stage 3 Breast Cancer [NCT00008203] | Phase 3 | 0 participants | Interventional | 1996-05-31 | Completed |
| A Randomized Phase II Study of Two Doses of Interferon Alfa-2a (IFN Alfa-2a) in Combination With Zidovudine (AZT) and Dideoxycytidine (ddC) Versus AZT and ddC Only in Patients With HIV Infection and Less Than 400 CD4 Cells/mm3 [NCT00000754] | Phase 2 | 60 participants | Interventional | | Completed |
| A Randomized Phase II Trial to Determine the Safety, Tolerance, and Efficacy of Two Doses of Interferon Alfa-2b Combined With Didanosine in Patients With Kaposi's Sarcoma [NCT00001114] | Phase 2 | 90 participants | Interventional | | Completed |
| A Phase II Pilot Study of Multi-Agent Neo-Adjuvant Chemoradiation in Patients With Locally Advanced Pancreatic Adenocarcinoma [NCT00262951] | Phase 2 | 23 participants (Actual) | Interventional | 2005-01-31 | Terminated(stopped due to Closed at a planned interim analysis by meeting a predefined toxicity endpoint) |
| Use of Hepatitis B Immune Globulin (HBIg) to Restore Immune Control in Patients With Chronic Hepatitis B [NCT03575208] | Phase 2 | 0 participants (Actual) | Interventional | 2019-02-13 | Withdrawn(stopped due to Slow/Insufficient accrual) |
| A Phase I/II Open Label Study To Evaluate the Antiviral Potential of Combination Low-Dose Therapy With Zidovudine and Interferon-Alpha 2A in Patients With Symptomatic HIV Disease [NCT00000696] | Phase 1 | 48 participants | Interventional | | Completed |
| A Phase I Study of AZT and Human Interferon Alpha (Recombinant Alpha-2A and Lymphoblastoid) in the Treatment of AIDS-Associated Kaposi's Sarcoma [NCT00001113] | Phase 1 | 48 participants | Interventional | | Completed |
| A Pilot Study of High Dose Busulfan Combined With IL2/GM-CSF Activated Autologous/Syngeneic PBSC, Sequential IL2/GM-CSF Therapy and Alpha Interferon Maintenance Therapy as Treatment of CML [NCT00005948] | Phase 2 | 0 participants | Interventional | 2000-01-31 | Completed |
| Phase III Randomized Trial of Interferon-Alfa2b Alone Versus Interferon-Alfa2b Plus Thalidomide in Patients With Previously Untreated Metastatic or Unresectable Renal Cell Carcinoma [NCT00005966] | Phase 3 | 0 participants | Interventional | 2000-10-31 | Completed |
| Treatment of Patients With Metastatic Malignant Melanoma With Chemobiotherapy With Temozolomide, GM-CSF, IL2, and Interferon Alfa-2b Phase II Trial [NCT00014092] | Phase 2 | 0 participants | Interventional | 1999-12-31 | Completed |
| Autologous Transplantation for Multiple Myeloma: A Research Study of Multiple Myeloma Using Chemotherapy Plus Growth Factor Primed Peripheral Blood Stem Cells Followed by Autologous Transplantation and Post-Transplant Immunotherapy [NCT00005987] | Phase 2 | 87 participants (Actual) | Interventional | 2000-08-31 | Terminated(stopped due to Withdrawn because treatment guidelines changed) |
| Study of Cerebral Function in Patients With Chronic Hepatitis C Infection Before and After Pegylated Interferon Alfa-2a and Ribavirin Therapy [NCT00788918] | | 100 participants (Actual) | Interventional | 2008-11-30 | Completed |
| Quality Assurance of HCV-therapy With PegIntron® Plus Rebetol® in Drug-substituted Patients - SUPPORT Project Post-Marketing Surveillance Study [NCT00726557] | | 246 participants (Actual) | Observational | 2005-10-31 | Completed |
| A Pilot Study in Comparing the Efficacy and Safety of Peginterferon Alfa-2a and Interferon Alfa-2a in Treating Patients With End Stage Renal Disease and Chronic Hepatitis C [NCT00172809] | Phase 4 | 50 participants (Actual) | Interventional | 2005-07-31 | Completed |
| Avonex Pregnancy Exposure Registry [NCT00168714] | | 329 participants (Actual) | Observational | 2004-02-29 | Completed |
| A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Avonex® in Subjects With Moderate to Severe Ulcerative Colitis [NCT00616434] | Phase 2 | 123 participants (Actual) | Interventional | 2008-05-31 | Completed |
| Improving Hepatitis C Treatment in Injection Drug Users [NCT00148031] | Phase 4 | 111 participants (Actual) | Interventional | 2003-09-30 | Completed |
| Pilot Study of Pegylated Interferon-Alfa 2b in Combination With PUVA Therapy in Cutaneous T-Cell Lymphoma [NCT00724061] | | 7 participants (Actual) | Interventional | 2008-09-30 | Terminated(stopped due to Closed early due to poor accrual.) |
| ANRS HC20 Pilot Study, Multicenter, Assessing the Effectiveness of an Optimized Anti HCV (360μg/Week Induction of PegIFN-alpha2a + 18mg/kg/j of RBV for 6 Months and Then Depending on the Virological Response to S12, Elongation up S72 to the Dual Anti HCV, [NCT00901524] | Phase 2 | 58 participants (Actual) | Interventional | 2009-06-30 | Completed |
| A Phase 3 Study of 2 Dose Regimens of Telaprevir in Combination With Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Treatment-Naive Subjects With Genotype 1 Chronic Hepatitis C [NCT00627926] | Phase 3 | 1,095 participants (Actual) | Interventional | 2008-03-31 | Completed |
| Clinical Trial of the Efficacy of Pegylated Interferon (PEG-IFNα-2a) Alone in Egyptian Patients With Acute Hepatitis C [NCT00158522] | Phase 3 | 31 participants (Actual) | Interventional | 2003-02-28 | Completed |
| Early Prediction of Successful Treatment for Chronic Hepatitis C Virus Infection in Taiwan [NCT00543244] | | 300 participants (Anticipated) | Observational | 2006-01-31 | Recruiting |
| Efficacy of High Doses of Both Pegylated Interferon Alfa-2a and Ribavirin for Retreatment of HIV-coinfected Patients With Liver Cirrhosis Due to HCV Genotype 1 or 4 Nonresponders to Previous Standard Therapy. [NCT01006031] | Phase 2/Phase 3 | 25 participants (Actual) | Interventional | 2009-10-31 | Completed |
| A Phase II, Multicenter, Randomized, Double Blind, Placebo Controlled, Safety, Tolerability and Efficacy Study of Add-on Cladribine Tablet Therapy With Interferon-beta (IFN-β) Treatment in Multiple Sclerosis Subjects With Active Disease [NCT00436826] | Phase 2 | 172 participants (Actual) | Interventional | 2006-11-30 | Completed |
| QOLBET Quality Of Life in Patients With Early Relapsing-remitting Multiple Sclerosis Treated With BETaferon® in Korea [NCT01071694] | | 0 participants (Actual) | Observational | 2011-01-31 | Withdrawn(stopped due to Study Manager could not embark on it during the timeline.) |
| Hepatitis C in a Cohort of Patients With Maintenance Therapy for Opiate Dependence - Prevalence, Severity and Outcome of Antiviral Therapy [NCT01045278] | Phase 4 | 277 participants (Actual) | Interventional | 2008-04-30 | Completed |
| Efficacy and Safety of 24 vs 48 Weeks of Pegetron® (Peginterferon Alfa-2b + Ribavirin) Therapy (1.5 mcg/kg/Week + 800-1200 mg/Day) in Naïve Genotype 1 Hepatitis C Patients With High Baseline Viral Load Who Are HCV-RNA Negative at Week 4 and Week 12 [NCT00423800] | Phase 3 | 56 participants (Actual) | Interventional | 2006-12-31 | Terminated(stopped due to The study was terminated due to difficulty in recruiting participants.) |
| A Prospective, Multi-center, Observational Study to Assess the Tolerability of Interferon-beta 1-A (Rebif®) Therapy for Korean Patients With Multiple Sclerosis [NCT01074346] | | 60 participants (Actual) | Observational | 2008-08-31 | Completed |
| A Study to Assess Treatment With PEG-Intron® and Rebetol® in Naïve Patients With Genotype 1 Chronic Hepatitis C and Slow Virological Response [NCT00265395] | Phase 3 | 1,428 participants (Actual) | Interventional | 2004-12-31 | Completed |
| An Open-label Extension Study of the Double-blind, Randomized, Parallel Group, Multicenter Phase 2 Study 307000A to Further Evaluate the Safety and Tolerability of Betaseron® 500 mcg Subcutaneously Every Other Day and Betaseron® 250 mcg Subcutaneously Eve [NCT00235989] | Phase 2 | 63 participants (Actual) | Interventional | 2003-06-30 | Completed |
| Multicentre, Single Arm, Open, Phase IV Study To Evaluate Immunogenicity And Safety Of Subcutaneous r-hIFN Beta-1a (Rebif®) Using Clone 484-39 In The Treatment Of Relapsing Remitting Multiple Sclerosis [NCT00367484] | Phase 4 | 460 participants (Actual) | Interventional | 2004-05-31 | Completed |
| An Open-label Study to Assess the Effect of First-line Treatment With Avastin in Combination With Standard Therapy on Progression-free Survival in Patients With Metastatic Renal Cell Cancer. [NCT00520403] | Phase 2 | 25 participants (Actual) | Interventional | 2007-09-30 | Completed |
| Open-label, Multi-center Phase III Extension of the Double-blind, Placebo-controlled BENEFIT Study (no. 92012/304747) to Obtain Long-term Follow-up Data of Patients With Clinically Definite Multiple Sclerosis (MS) and Patients With a First Demyelinating E [NCT00185211] | Phase 3 | 468 participants (Actual) | Interventional | 2002-08-31 | Completed |
| Phase II Trial of the Effects of Interferon Alfa-2b on the Immunogenicity of a Polyvalent Melanoma Antigen Vaccine in Patients With Stage III Malignant Melanoma [NCT00004104] | Phase 2 | 0 participants | Interventional | 1998-06-30 | Completed |
| Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-986165 in Healthy Subjects and to Evaluate the Safety, Tolerability, Pharmacokinetic [NCT02534636] | Phase 1 | 140 participants (Actual) | Interventional | 2015-10-31 | Completed |
| A Phase III Study of STI571 Versus Interferon-α (IFN-α) Combined With Cytarabine (Ara-C) in Patients With Newly Diagnosed Previously Untreated Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) [NCT00333840] | Phase 3 | 1,106 participants (Actual) | Interventional | 2000-06-30 | Completed |
| Evaluation of Natural Human Interferon Alpha Administered Oromucosally in the Treatment of Oral Warts in HIV-seropositive Subjects Receiving Combination Anti-retroviral Therapy: A Phase 2 Clinical Trial [NCT00454181] | Phase 2 | 59 participants (Actual) | Interventional | 2007-02-28 | Completed |
| Randomized Multicenter Phase III Study Comparing the Rate of Molecular Response 4.5 at 12 Months in Newly Diagnosed Philadelphia Positive Chronic Phase Chronic Myelogenous Leukemia Patients Receiving Either Frontline Nilotinib 600 mg Daily or Nilotinib 60 [NCT02201459] | Phase 3 | 200 participants (Anticipated) | Interventional | 2014-08-31 | Recruiting |
| Medical Ozone Versus Conventional Interferon-α Treatment of Patients With Chronic Hepatitis B -A Control Study to Evaluate The Efficacy And Safety of Ozone-therapy in Chronic Hepatitis B [NCT01887275] | Phase 4 | 439 participants (Actual) | Interventional | 2010-03-31 | Completed |
| Treatment of Acute Hepatitis C Virus Infection in Injection Drug Users With Pegylated Interferon for 24 Weeks [NCT00194480] | Phase 4 | 21 participants (Actual) | Interventional | 2003-04-30 | Completed |
| Phase 1 Study to Evaluate the Feasibility and Efficacy of the Addition of P1101 (PEG-Proline-Interferon Alpha-2b) to Imatinib Treatment in Patients With Chronic Phase Chronic Myeloid Leukaemia Not Achieving a Complete Molecular Response (MR 4.5 or BCR-ABL [NCT01933906] | Phase 1 | 12 participants (Actual) | Interventional | 2013-08-30 | Completed |
| Does Induction PEG-Intron in Combination With Rebetol Enhance the Sustained Response Rates in Patients With Chronic Hepatitis C [NCT00207363] | Phase 4 | 610 participants (Actual) | Interventional | 2002-02-28 | Completed |
| A Pilot Trial of Combination Therapy With Interferon Alfacon1, Ribavirin, & Rosiglitazone in a Group of Insulin Resistant, Chronic Hepatitis C, GT 1 Patients Who Are Previous Relapsers or Nonresponders to Pegylated Interferon and Ribavirin [NCT00207402] | Phase 4 | 34 participants (Actual) | Interventional | 2005-10-31 | Completed |
| A Phase I/II Study of the SV-BR-1-GM Regimen in Metastatic or Locally Recurrent Breast Cancer Patients in Combination With Retifanlimab [NCT03328026] | Phase 1/Phase 2 | 36 participants (Anticipated) | Interventional | 2018-03-16 | Enrolling by invitation |
| Effectiveness of Pegylated Interferon Plus Ribavirin in the Treatment of Active and Past Intravenous Drug Users Infected With Hepatitis C [NCT00203606] | Phase 4 | 66 participants (Actual) | Interventional | 2004-01-31 | Completed |
| Randomized, Double-Blind, Multicenter Study to Compare the Safety and Efficacy of Viramidine to Ribavirin in Treatment-Naive Patients With Chronic Hepatitis C [NCT00230958] | Phase 3 | 900 participants | Interventional | 2003-12-31 | Completed |
| Dose-seeking and Efficacy Study of the Combination of the BRAF Inhibitor Vemurafenib and High-dose Interferon Alfa-2b for Therapy of Advanced Melanoma [NCT01943422] | Phase 1 | 7 participants (Actual) | Interventional | 2013-10-31 | Completed |
| A PHASE II STUDY OF MITOXANTRONE AND HIGH-DOSE ARA-C FOLLOWED BY INTENSIVE CONSOLIDATION WITH CYCLOPHOSPHAMIDE AND ETOPOSIDE FOR MYELOID BLAST CRISIS OF CHRONIC MYELOGENOUS LEUKEMIA (CML) [NCT00002598] | Phase 2 | 30 participants (Anticipated) | Interventional | 1994-06-30 | Completed |
| New Immunomodulatory Therapy Strategies in Chronic Reactive Arthritis: Immunostimulation Plus Antibiotic Versus Immunosuppression Plus Antibiotic Versus Conventional Standardtherapy [NCT00244179] | Phase 2 | 40 participants | Interventional | 2003-01-31 | Recruiting |
| A Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-Tricom (B7.1/ICAM/LFA3) and Vaccinia-CEA (6D)-Tricom, in Combination With GM-CSF and Interferon-Alfa-2B in Patients With CEA-Expressing Carcinomas [NCT00217373] | Phase 1 | 33 participants (Actual) | Interventional | 2005-06-30 | Completed |
| A Phase 2 Study Of BAY 43-9006 In Combination With Interferon Alfa-2b In Metastatic Renal Cell Cancer [NCT00098618] | Phase 2 | 40 participants (Actual) | Interventional | 2004-10-31 | Terminated |
| A Pilot Study of Aerosol Interferon-gamma for Treatment of Idiopathic Pulmonary Fibrosis [NCT00563212] | Phase 1 | 12 participants (Actual) | Interventional | 2007-01-31 | Completed |
| A Multicentre, Open Label, Non-Comparative Trial Investigating the Recovering of INF-Beta Efficacy in Breakthrough Relapsing-Remitting Multiple Sclerosis Patients With Neutralizing Interferon-Beta Antibodies [NCT00492466] | Phase 4 | 14 participants (Actual) | Interventional | 2003-03-31 | Completed |
| Effect of Long-term Vitamin D Therapy on IL-6, Visfatin and Hyaluronic Acid in Hepatitis C Virus Patients' Assessment [NCT01997203] | Phase 3 | 100 participants (Actual) | Interventional | 2012-04-30 | Terminated(stopped due to complete patients samples required) |
| Phase Ib Study of Recombinant Human Serum Albumin/Interferon alpha2a Fusion Protein in Chronic Hepatitis B Patients [NCT01997944] | Phase 1/Phase 2 | 32 participants (Actual) | Interventional | 2013-11-30 | Completed |
| Phase II Study of Nilotinib Plus Pegylated Interferon Alfa-2b as First-line Therapy in Chronic Phase Chronic Myelogenous Leukaemia Aiming to Maximize Complete Molecular Response and Major Molecular Response. [NCT02001818] | Phase 2 | 100 participants (Anticipated) | Interventional | 2014-04-30 | Recruiting |
| Pegasys and Copegus for Asian Patients With Treatment-naive Hepatitis C Genotypes 6, 7, 8, 9: a Phase IV, Randomized, Open-labeled, Multicenter Trial Comparing 24-week vs. 48-week Therapy [NCT00575224] | Phase 4 | 60 participants (Actual) | Interventional | 2004-10-31 | Completed |
| Role of A. Lumbricoides in the Development of Pulmonary Aspergillosis in Chronic Obstructive Pulmonary Disease Patients [NCT05783544] | | 200 participants (Anticipated) | Interventional | 2015-05-01 | Recruiting |
| A Phase III, Open-label Trial in Japan to Investigate the Efficacy and Safety of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Genotype 1, Hepatitis C-infected Subjects Who Relapsed After Previous IFN-based Therapy [NCT01290731] | Phase 3 | 49 participants (Actual) | Interventional | 2011-01-31 | Completed |
| A Randomized, Open-Label, Phase 3 Study of Telaprevir Administered Twice Daily or Every 8 Hours in Combination With Pegylated Interferon Alfa-2a and Ribavirin in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C Virus Infection [NCT01241760] | Phase 3 | 744 participants (Actual) | Interventional | 2010-12-31 | Completed |
| [NCT02027064] | Phase 4 | 40 participants (Anticipated) | Interventional | 2013-10-31 | Recruiting |
| Safety and Efficacy of Hansenula-Derived Pegylated-Interferon Alpha-2a and Ribavirin Customized Combination Therapy in Egyptian Children With Chronic Hepatitis C Infection [NCT02027493] | | 46 participants (Actual) | Interventional | 2009-02-28 | Completed |
| A Phase IIa Clinical Trial to Test the Safety and Efficacy of Interferon Gamma Treatment in Elevating Frataxin Levels in Friedreich's Ataxia (FRDA) Patients [NCT02035020] | Phase 2 | 10 participants (Actual) | Interventional | 2013-05-31 | Completed |
| A Phase I/II Pilot Study of Bioimmunotherapy With IRESSA (Gefitinib) and Pegylated Interferon Alpha-2a for Patients With Unresectable/Metastatic Squamous Cell Carcinoma of the Skin [NCT00423397] | Phase 1/Phase 2 | 16 participants (Anticipated) | Interventional | 2006-09-30 | Active, not recruiting |
| A Prospective, Multicenter, Phase II/III, Open-Label, Controlled, Randomized Trial Evaluating the Efficacy, Safety, and Tolerability of Interferon-alfa-2a Plus Ribavirin Versus PEG-interferon-alfa-2a Plus Ribavirin for Chronic Hepatitis C Virus (HCV) Infe [NCT00008463] | Phase 2 | 132 participants | Interventional | 2000-11-30 | Completed |
| PHASE I/II STUDY OF IMMUNIZATION WITH MHC CLASS I MATCHED ALLOGENEIC HUMAN PROSTATIC CARCINOMA CELLS ENGINEERED TO SECRETE INTERLEUKIN-2 AND INTERFERON-GAMMA [NCT00002637] | Phase 1/Phase 2 | 25 participants (Anticipated) | Interventional | 1995-01-31 | Completed |
| Phase II Study of Zidovudine and Recombinant Alpha-2A Interferon in the Treatment of Patients With AIDS-Associated Kaposi's Sarcoma [NCT00000687] | Phase 2 | 60 participants | Interventional | | Completed |
| Inhaled Interferon α2b Treatment in Mild-to-moderate COVID-19 Infected Children [NCT05381363] | Phase 1/Phase 2 | 24 participants (Actual) | Interventional | 2022-01-01 | Terminated(stopped due to The study was concluded as planned upon reaching its predetermined endpoint, which included the completion of data collection and achievement of the necessary sample size for statistical significance.) |
| A Phase II Study of an Anti-Tumor Immunotherapy Regimen Comprised of Pegylated Interferon-Alpha 2b (PEG-Intron)and HyperAcute Melanoma Vaccine for Subjects With Advanced Melanoma [NCT00746746] | Phase 2 | 30 participants (Anticipated) | Interventional | 2008-06-30 | Active, not recruiting |
| An Open-Label Study to Examine the Difference in Tolerability Associated With Titration Of Dose on Initiation of Avonex therapY (TODAY) [NCT00574041] | Phase 4 | 19 participants (Actual) | Interventional | 2007-06-30 | Terminated(stopped due to Terminated due to poor recruitment) |
| Treatment of Chronic Hepatitis C Patients With Persistently Normal Alanine Aminotransferase Levels With Peginterferon α-2a (40 kDa) Plus Ribavirin [NCT00575627] | Phase 4 | 150 participants (Anticipated) | Interventional | 2007-09-30 | Recruiting |
| A Pilot Study of Differentiation Therapy in Multiple Myeloma Using Interleukin-6 and Interferon-a [NCT00470093] | Early Phase 1 | 3 participants (Actual) | Interventional | 2007-10-31 | Terminated(stopped due to Low accrual) |
| A Comparative Study of the Efficacy of Transcatheter Arterial Chemoembolization (TACE) and Transcatheter Arterial Pegylated Interferon Embolization (TAIE) for Hepatocellular Carcinoma [NCT00563095] | | 100 participants (Anticipated) | Interventional | 2004-03-31 | Recruiting |
| A Phase 2 Study of Capecitabine or 5-FU With Pegylated Interferon Alpha-2b in Unresectable/Metastatic Cutaneous Squamous Cell Carcinoma [NCT02218164] | Phase 2 | 8 participants (Actual) | Interventional | 2014-08-12 | Completed |
| Randomized Controlled Open Label Trial of Peg Alpha 2a Interferon and Adjusted-dose of Ribavirin vs. Standard Therapy in the Treatment of Naive Chronic Hepatitis C Patients Infected With Genotype 4 [NCT01686789] | Phase 4 | 181 participants (Actual) | Interventional | 2011-01-31 | Completed |
| A Multicentre, Randomised, Double-blind, Placebo-controlled Study of the Efficacy of Supplementary Treatment With Cholecalciferol (Vitamin D3) in Patients With Relapsing- Multiple Sclerosis (RMS) Treated With Subcutaneous Interferon Beta-1a 44 µg 3 Times [NCT01198132] | Phase 2 | 129 participants (Actual) | Interventional | 2009-11-30 | Completed |
| A Multi-center, Open-label, Single-arm, Before and After Switch Study to Evaluate the Efficacy, Safety and Tolerability of Alemtuzumab in Paediatric Patients With Relapsing Remitting Multiple Sclerosis (RRMS) With Disease Activity on Prior Disease Modifyi [NCT03368664] | Phase 3 | 16 participants (Actual) | Interventional | 2017-10-24 | Active, not recruiting |
| BETAPREDICT - MS Patients Treated With BETAferon®: PREDICTors of Treatment Adherence [NCT02486640] | | 162 participants (Actual) | Observational | 2015-09-08 | Completed |
| Phase I Clinical Trial Assessing the Combination of Chemokine Modulation With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer [NCT04081389] | Phase 1 | 9 participants (Actual) | Interventional | 2019-12-06 | Completed |
| Phase I Trial to Evaluate the Safety and Efficacy of Intratumoral and Intravenous Injection of Vesicular Stomatitis Virus Expressing Human Interferon Beta and Tyrosinase Related Protein 1 (VSV-IFNb-TYRP1) in Patients With Metastatic Ocular Melanoma and Pr [NCT03865212] | Phase 1 | 12 participants (Actual) | Interventional | 2019-06-12 | Active, not recruiting |
| Systemic Therapy of Metastatic Melanoma With Multidrug Regimen Including Interferon, Interleukin-2 and BRAF Inhibitor [NCT01603212] | Phase 1 | 6 participants (Actual) | Interventional | 2013-07-18 | Completed |
| Phase I Clinical Trial of PEG-IFN-SA in HCV Disease: Evidence for Drug Safety, Tolerance, and Antiviral Activity [NCT01605513] | Phase 1/Phase 2 | 80 participants (Actual) | Interventional | 2011-06-30 | Completed |
| An Open-Label, 3-Panel, Dose-Escalation Study to Assess the Safety and Tolerability, Pharmacokinetics, and Viral Kinetics of Two Doses of LocteronTM (Poly ActiveTM - Interferon Alpha 2b) Given Every 2 Weeks for 4-12 Weeks in Comparison With PEG-Intron Giv [NCT00593151] | Phase 1/Phase 2 | 32 participants (Actual) | Interventional | 2008-01-31 | Completed |
| A Multicenter, Prospective and Retrospective, Long-Term Observational Study of AVONEX® and Rebif® to Determine the Efficacy, Tolerability, and Safety in Subjects With Relapsing Multiple Sclerosis (MS) [NCT00599274] | | 136 participants (Actual) | Observational | 2002-08-31 | Completed |
| A Multicenter, Randomized, Controlled Study Comparing the Efficacy and Safety of 48 Weeks of 40kD Branched Pegylated Interferon Alfa-2a (PEG-IFN, RO 25-8310) Versus 96 Weeks of PEG-IFN, Alone or in Combination With 100 mg Lamivudine for 48 Weeks in Patien [NCT01095835] | Phase 3 | 131 participants (Actual) | Interventional | 2005-02-28 | Completed |
| A Blinded, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety, Pharmacokinetics, and Antiviral Activity of ABT-267 in Combination With Peginterferon Alpha-2a and Ribavirin (pegIFN/RBV) in Treatment-Naïve Subjects With Genotype 1 Chr [NCT01314261] | Phase 2 | 37 participants (Actual) | Interventional | 2011-03-31 | Completed |
| Combined Treatment of Sorafenib and Pegylated Interferon α2b in Stage IV Metastatic Melanoma: a Prospective Non-randomized, Multicenter Phase II Study [NCT00623402] | Phase 2 | 55 participants (Anticipated) | Interventional | 2008-01-31 | Completed |
| Physical Disability Observational Study in Patients Treated With Betaferon in Daily Practice [NCT00873340] | | 83 participants (Actual) | Observational | 2007-10-31 | Completed |
| A Phase II Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Different Regimens of MK7009 When Administered Concomitantly With Pegylated Interferon and Ribavirin in Treatment-Naive Patients With Chronic Genotype 1 [NCT00895882] | Phase 2 | 0 participants (Actual) | Interventional | 2010-11-30 | Withdrawn |
| Title: Evaluation of Systemic IDO Levels After Various Immunotherapeutics [NCT00897312] | | 7 participants (Actual) | Observational | 2006-10-31 | Terminated(stopped due to slow accrual) |
| Association of Rituximab to Immunochemotherapy With CVP + Interferon in Newly Diagnosed Follicular Lymphoma Patients With Intermediate-high FLIPI Score. Phase II Study. [NCT00842114] | Phase 2 | 50 participants (Actual) | Interventional | 2006-02-28 | Completed |
| An Open-label, Randomized Study of PegIntron in the Treatment of HBeAg Positive Chronic Hepatitis B Patients [NCT00536263] | Phase 3 | 671 participants (Actual) | Interventional | 2007-09-30 | Completed |
| A Double-blind Placebo Controlled Trial Using Subcutaneous Injections of Intron A for the Treatment of Hypertrophic Scar [NCT00686478] | Phase 3 | 0 participants (Actual) | Interventional | | Withdrawn(stopped due to The trial is not being done at this time) |
| Study of Systematic Tuberculosis Testing for Active, Sub-clinical and Latent Tuberculosis Infection in a United Kingdom Human Immunodeficiency Virus (HIV) Infected Cohort [NCT02712671] | | 300 participants (Anticipated) | Observational | 2013-06-30 | Active, not recruiting |
| A Phase 2 Study of Type-1 Polarized Dendritic Cell (αDC1) Vaccine in Combination With Tumor-Selective Chemokine Modulation (Interferon-α2b, Rintatolimod, and Celecoxib) in Subjects With Chemo-Refractory Metastatic Colorectal Cancer [NCT02615574] | Phase 2 | 0 participants (Actual) | Interventional | 2016-03-31 | Withdrawn(stopped due to Due to inadequate supply of drug) |
| Open, Randomized and Multicenter Phase IV Study to Compare the Efficacy and Safety of Two Different Treatments Duration 24 Versus 48 Weeks in Chronic Hepatitis C Genotypes 2 and/or 3 co-Infected HIV-HCV Patients. [NCT00611819] | Phase 4 | 59 participants (Actual) | Interventional | 2005-11-30 | Active, not recruiting |
| Australian Trial in Acute Hepatitis C [NCT00192569] | Phase 4 | 167 participants (Actual) | Interventional | 2004-07-31 | Completed |
| Randomized Phase II Neoadjuvant Study of Temozolomide Alone or With Pegylated Interferon-alpha 2b in Patients With Resectable American Joint Committee on Cancer (AJCC) Stage IIIB/IIIC or Stage IV (M1a) Metastatic Melanoma [NCT00525031] | Phase 2 | 55 participants (Actual) | Interventional | 2006-08-31 | Completed |
| Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis [NCT00616187] | Phase 2 | 41 participants (Actual) | Interventional | 2003-10-31 | Completed |
| International, Multicenter, Double-blinded, Placebo-controlled, Randomized Study of the Efficacy and Safety of Drugs BCD-033 and Rebif for the Treatment of Patients With Relapsing-remitting Multiple Sclerosis [NCT02727907] | Phase 2/Phase 3 | 163 participants (Actual) | Interventional | 2015-02-12 | Completed |
| Retreatment of Dialysis Patients With Chronic Hepatitis C With Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin Who Fail Interferon Alfa or Pegylated Interferon Alfa Monotherapy - a Pilot Study [NCT00491179] | Phase 4 | 35 participants (Actual) | Interventional | 2006-06-30 | Completed |
| A Phase II of Randomized, Double-blind, Placebo-controlled, Multi-center Study of Hepalatide for Injection Combined With Pegylated Interferon and TAF as Finite Treatment in Chronic Hepatitis B Patients [NCT05244057] | Phase 2 | 30 participants (Anticipated) | Interventional | 2022-08-23 | Recruiting |
| A Multi-center Double-blind Parallel-group Placebo-controlled Study of the Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis Who Are Treated With Interferon-beta [NCT01252355] | Phase 3 | 534 participants (Actual) | Interventional | 2011-01-31 | Terminated(stopped due to Sponsor decision to prematurely stop the study, not linked to any safety concern.) |
| A Phase I Study Of Peginterferon Alfa-2b (PEG-INTRON) With Sorafenib (Nexavar) In Patients With Unresectable Or Metastatic Clear Cell Renal Carcinoma (RCC). [NCT00589550] | Phase 1 | 1 participants (Actual) | Interventional | 2008-02-29 | Terminated(stopped due to low accrual) |
| A Phase I, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sodium Stibogluconate in Combination With Interferon Alpha-2b for Patients With Advanced Malignancies [NCT00629200] | Phase 1 | 33 participants (Actual) | Interventional | 2006-09-13 | Completed |
| An Open-label, Dose-ranging, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Lonafarnib With and Without Ritonavir Boosting in Patients Chronically Infected With Delta Hepatitis (HDV) (LOWR-1) [NCT02430181] | Phase 2 | 21 participants (Actual) | Interventional | 2014-11-30 | Completed |
| A Phase I/II Study of Intratumoral Dendritic Cell Vaccination Combined With Local Radiotherapy in Patients With Recurrent Lymphoma. [NCT00637117] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2008-07-31 | Withdrawn(stopped due to The study never opened and not sure if it ever will.) |
| Impact of the BETACONNECT Auto-injector on BETASERON Therapy Adherence and Patient Satisfaction [NCT02652091] | | 146 participants (Actual) | Observational | 2016-02-05 | Completed |
| A Phase II Open Label Study of MK-7009 Administered Concomitantly With Pegylated Interferon Alfa-2a and Ribavirin to Patients With Chronic Hepatitis C Infection After Participation in Other MK-7009 Clinical Trials [NCT00943761] | Phase 2 | 45 participants (Actual) | Interventional | 2009-10-23 | Completed |
| Prospective Study of the Molecular Characteristics of Sensitive and Resistant Disease in Patients With HTLV-I Associated Adult T Cell Leukemia Treated With Zidovudine (AZT) Plus Interferon Alpha-2b [NCT00854581] | Phase 4 | 13 participants (Actual) | Interventional | 2007-11-30 | Terminated(stopped due to Investigator Decision) |
| The Safety and Cost-effectiveness of Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS): a Randomized Rater-blinded Multicenter Trial. [NCT04260711] | | 130 participants (Anticipated) | Interventional | 2020-07-01 | Recruiting |
| A Phase III, Randomised, Open-label, Multicenter International Trial Comparing Ruxolitinib With Either HydRoxycarbamIDe or Interferon Alpha as First Line ThErapy for High Risk Polycythemia Vera [NCT04116502] | Phase 3 | 586 participants (Anticipated) | Interventional | 2019-10-25 | Recruiting |
| Pilot Trial of Interferon Beta-1a in Alzheimer's Disease [NCT01075763] | Phase 2 | 42 participants (Actual) | Interventional | 2004-11-30 | Completed |
| A Prospective Study of Peginterferon Alfa-2a and Ribavirin: Outcomes Assessment in Chronic Hepatitis C Patients [NCT02850289] | | 385 participants (Actual) | Observational | 2006-04-30 | Completed |
| De-escalation After Natalizumab Treatment With Interferon-beta-1b in Patients With Relapsing-remitting Multiple Sclerosis [NCT01144052] | Phase 4 | 19 participants (Actual) | Interventional | 2010-06-30 | Completed |
| The Response and Outcomes of Pegylated Interferon Plus Ribavirin Combination Therapy for Chronic Hepatitis C Patients Concomitant With Malignancy Other Than Hepatocellular Carcinoma [NCT00630084] | Phase 4 | 120 participants (Actual) | Interventional | 2006-08-31 | Completed |
| MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b: a Multicenter, Placebo-controlled, Double-blind Randomized Trial [NCT02845843] | Phase 2/Phase 3 | 95 participants (Actual) | Interventional | 2016-07-31 | Completed |
| Cohort Study of Clinical Outcomes in Chronic HBV Infection Patients With Low HBsAg Loads Under Unplanned Intervention [NCT04030039] | | 420 participants (Anticipated) | Observational | 2017-05-01 | Recruiting |
| Efficacy and Safety of Pegylated Interferon Plus Ribavirin Combination Therapy in Treating Older Patients With Chronic Hepatitis C [NCT00629824] | Phase 4 | 250 participants (Anticipated) | Interventional | 2007-02-28 | Completed |
| A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of PEGylated Interferon Beta-1a (BIIB017) in Subjects With Relapsing Multiple Sclerosis [NCT00906399] | Phase 3 | 1,516 participants (Actual) | Interventional | 2009-06-30 | Completed |
| Efficacy and Safety of High-dose Vitamin C Combined With Traditional Chinese Medicine in the Treatment of Moderate and Severe Coronavirus Pneumonia (COVID-19) [NCT04664010] | | 30 participants (Actual) | Interventional | 2020-02-06 | Completed |
| Interferon-gamma With Interferon Alpha and Ribavirin for Hepatitis C Patients Who Are Non-responders to Interferon Alpha Plus Ribavirin [NCT00538811] | Phase 2/Phase 3 | 40 participants (Anticipated) | Interventional | | Completed |
| Randomized, Double-blind, Parallel, Controlled Clinical Study to Evaluated the Efficacy and Safety of Recombinant Human Interferon Alpha-2b Gel (Yallaferon®) in HPV-16 and/or HPV-18 Infection [NCT02801383] | Phase 2/Phase 3 | 100 participants (Anticipated) | Interventional | 2015-09-30 | Recruiting |
| Treatment of Chronic Hepatitis With Sofosbuvir in Combination With Ribavirin With or Without Pegylated Interferon: North India Gastroenterology Consortium [NCT02799355] | | 1,203 participants (Actual) | Observational | 2016-05-31 | Completed |
| "WHO Public Health Emergency Solidarity Clinical Trial for COVID-19 Treatments" [NCT04647669] | Phase 3 | 100 participants (Anticipated) | Interventional | 2021-06-01 | Not yet recruiting |
| Extension Study of the BENEFIT (304747) and BENEFIT Follow-up (305207) Studies to Further Evaluate the Progress of Patients With First Demyelinating Event Suggestive of Multiple Sclerosis [NCT00544037] | | 283 participants (Actual) | Observational | 2007-09-30 | Completed |
| A Phase 1 Study to Assess the Safety and Antiviral Activity of PEG-rIL-29 Administered as a Single Agent and in Combination With Ribavirin in Treatment-Relapsed and Treatment-Naive Subjects With Chronic Hepatitis C Virus Infection [NCT00565539] | Phase 1 | 56 participants (Actual) | Interventional | 2007-12-31 | Completed |
| IPI-Biochemotherapy for Chemonaive Patients With Metastatic Melanoma [NCT01409174] | Phase 1 | 19 participants (Actual) | Interventional | 2013-02-28 | Terminated(stopped due to Slow accrual, closed in Phase I.) |
| Betaferon® Regulatory Post-Marketing Surveillance [NCT01414816] | | 355 participants (Actual) | Observational | 2008-04-30 | Completed |
| A Multi-centre Randomised Controlled Double-blinded Trial of BCG and Interferon Alpha in High Risk Superficial Bladder Cancer [NCT00330707] | Phase 2/Phase 3 | 140 participants | Interventional | 1995-10-31 | Completed |
| A Multiple-Dose, Open-Label, Phase 1, Pharmacokinetic, Pharmacodynamic, and Safety Study of Avonex® in Chinese Healthy Volunteer Subjects [NCT01416207] | Phase 1 | 24 participants (Actual) | Interventional | 2011-08-31 | Completed |
| Double-Blind, Placebo-Controlled, Randomized, Parallel Group, Multicenter Study to Evaluate Efficacy and Safety of 4 and 8 Million Units Betaferon®/Betaseron® (Interferon Beta-1b) Given Subcutaneously Every Other Day Over 24 Weeks in Patients With Chronic [NCT00185250] | Phase 2 | 138 participants (Actual) | Interventional | 2002-12-31 | Completed |
| A Randomized Phase II Study of SCH 54031 in Surgically Resectable Squamous Cell Tumors of the Head and Neck [NCT00276523] | Phase 2 | 3 participants (Actual) | Interventional | 2004-02-29 | Completed |
| Fotemustine and Dacarbazine Versus Dacarbazine +/- Alpha Interferon in Advanced Malignant Melanoma: Phase III Study [NCT01359956] | Phase 3 | 269 participants (Actual) | Interventional | 2002-04-30 | Completed |
| A Phase I/II Study to Evaluate the Optimum Dose of Pegylated-Interferon (PEG INTRON) in Patients With Platinum Resistant Ovarian, Peritoneal or Fallopian Tube Cancer [NCT00085384] | Phase 1/Phase 2 | 30 participants (Actual) | Interventional | 2002-07-31 | Terminated(stopped due to Terminated due to slow accrual.) |
| A Phase II Trial of a MART-1/gp100/Tyrosinase Peptide-Pulsed Dendritic Cell Vaccine Treated With CD40 Ligand/Gamma Interferon With Subcutaneous IL-2 for Patients With Metastatic Melanoma [NCT00006113] | Phase 2 | 25 participants (Actual) | Interventional | 1999-06-30 | Terminated(stopped due to Lack of efficacy) |
| A Phase 2b Study of Merimepodib in Combination With Pegylated Interferon Alfa-2a (Pegasys®) and Ribavirin in Subjects With Chronic Hepatitis C Non-Responsive to Prior Therapy With Pegylated Interferon Alfa and Ribavirin [NCT00088504] | Phase 2 | 315 participants | Interventional | 2004-07-31 | Completed |
| Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis [NCT03535298] | Phase 4 | 800 participants (Anticipated) | Interventional | 2019-01-03 | Recruiting |
| A Phase II Clinical Trial of Cisplatin + Gemcitabine HCl (GEM) + Low-Dose Metronomic Interferon-a (IFN-a) Combined With Fever-Range Whole-Body Thermal Therapy (FR-WB-TT) in Patients With Metastatic/or Locally Advanced Malignancies (Small-Cell Lung Cancer, [NCT00178698] | Phase 2 | 36 participants (Anticipated) | Interventional | 2002-07-31 | Recruiting |
| Multicentric Trial Comparing Three Therapeutical Strategies in Patients With Acute Primary HIV Infection.ANRS 112 INTERPRIM [NCT00196638] | Phase 2/Phase 3 | 90 participants | Interventional | 2002-05-31 | Terminated |
| Efficacy of Low Dose Pegylated Interferon-α 2a Plus Ribavirin for the Treatment of Chronic Hepatitis C, Genotypes 2 or 3, in HIV-coinfected Patients. [NCT00553930] | Phase 4 | 71 participants (Anticipated) | Interventional | 2007-11-30 | Completed |
| A Phase I/II Study of Interferon Gamma-1b by Inhalation for the Treatment of Patients With Cystic Fibrosis [NCT00043316] | Phase 1/Phase 2 | 66 participants (Actual) | Interventional | 2001-02-28 | Completed |
| Phase 2 Study of Omega Interferon Alone or in Combination With Ribavirin in Subjects With Hepatitis C [NCT00097045] | Phase 2 | 90 participants | Interventional | 2004-11-30 | Completed |
| Recombinant Human Interferon Beta-1a in Acute Ischemic Stroke: A Dose Escalation and Safety Study [NCT00097318] | Phase 1 | 60 participants (Anticipated) | Interventional | 2004-11-17 | Completed |
| An Open-Label, Multicenter Study to Determine Subject Satisfaction in Using the Single-Use Autoinjector With a Pre-Filled Liquid AVONEX® Syringe in Multiple Sclerosis Subjects [NCT00915577] | Phase 3 | 74 participants (Actual) | Interventional | 2005-08-31 | Completed |
| An Observational Cohort Study of Clinical Outcomes After Antiviral Treatment of Chronic Hepatitis C Patients [NCT04301882] | | 1,000 participants (Anticipated) | Observational [Patient Registry] | 2019-09-01 | Recruiting |
| Efficacy and Safety of Interferon Based Therapy and Interferon-free Direct-acting Antivirals in Cirrhotic Patients With Hepatitis C. Impact of Antiviral Therapy on Gastroesophageal Varices. [NCT02758509] | | 237 participants (Actual) | Observational | 2010-01-01 | Completed |
| Randomized Treatment Interruption of Natalizumab [NCT01071083] | Phase 2 | 175 participants (Actual) | Interventional | 2010-03-31 | Completed |
| Efficacy and Safety of Azacitidine Combined With Interferon in the Treatment of Recurrence of Allogeneic Hematopoietic Stem Cell Transplantation in Myeloid Tumors of the Blood System [NCT04078399] | | 30 participants (Anticipated) | Interventional | 2019-08-28 | Recruiting |
| Phase II Clinical Trial of Cisplatin + Gemcitabine in Combination With Mild, Fever-Range Whole-Body Hyperthermia to Treat Patients With Advanced, Inoperable Pancreatic Cancer [NCT00178763] | Phase 2 | 36 participants (Anticipated) | Interventional | 2003-09-30 | Recruiting |
| Intron-A/Aldara Combination Therapy for BCC Excluding the Face and Scalp [NCT00581425] | Phase 4 | 49 participants (Actual) | Interventional | 2007-12-31 | Completed |
| A Phase II Study of the RAF-Kinase Inhibitor BAY 43-9006 (NSC-724772, IND-69,896) in Combination With Interferon-Alpha 2B in Patients With Advanced Renal Cancer [NCT00101114] | Phase 2 | 55 participants (Actual) | Interventional | 2004-09-30 | Completed |
| A Phase II Trial of Oxaliplatin/Adriamycin/5 Fluorouracil in Continuous Infusion / Interferon α-2b (OXAFI) Combination as Neoadjuvant Therapy in Unresectable Non-Metastatic Hepatocellular Carcinoma [NCT00471484] | Phase 2 | 54 participants (Anticipated) | Interventional | 2007-03-31 | Recruiting |
| Clinical Trial of the Efficacy of the Combination of Pegylated Interferon (PEG-IFNα-2a) Plus Ribavirin in Egyptian Patients With Untreated Chronic Hepatitis C [NCT00158496] | Phase 3 | 100 participants | Interventional | 2002-08-31 | Completed |
| A Phase 1 Study of 5-azacitidine in Combination With Interferon-Alfa 2B in Unresectable or Metastatic Melanoma and Renal Cell Carcinoma [NCT00217542] | Phase 1 | 42 participants (Actual) | Interventional | 2005-07-31 | Completed |
| Factors Associated to Success of Hepatitis C Therapy [NCT00514111] | | 100 participants (Actual) | Observational | 2007-08-31 | Completed |
| A Prospective, Randomized, Double-blind, Double-simulated, Placebo Parallel-controlled, Multicenter Clinical Study on Safety and Efficacy of Recombinant Human Interferon ω Spray in Treatment of Viral Upper Respiratory Tract Infection in Children [NCT05859984] | Phase 2 | 345 participants (Anticipated) | Interventional | 2023-05-31 | Not yet recruiting |
| Safety and Efficacy of Recombinant Interferon-Gamma 1b (rIFN-Gamma 1b) Given With Standard Therapy in Patients With Candidemia [NCT04979052] | Phase 2 | 200 participants (Anticipated) | Interventional | 2022-03-31 | Recruiting |
| A Phase III, Randomised, Open Label, Active-controlled Study of an Interferon-free Regimen of BI 207127 in Combination With Faldaprevir and Ribavirin Compared to Telaprevir in Combination With Pegylated interferon-a and Ribavirin in Treatment-naive Patien [NCT01858961] | Phase 3 | 0 participants (Actual) | Interventional | 2013-05-31 | Withdrawn |
| Pegylated Interferon Alfa-2a Versus Emtricitabine / Tenofovir +/- Pegylated Interferon Alfa-2a for the Treatment of Chronic HBe-Ag Positive Hepatitis B Infection in HIV-Coinfected Patients - the PEGPLUS Trial [NCT00221286] | Phase 3 | 2 participants (Actual) | Interventional | 2004-09-30 | Terminated(stopped due to Lack of accrual) |
| A Single-centre Study to Evaluate the Tolerability, Pharmacokinetics, and Pharmacodynamics of a New Inhaled Formulation of AVONEX® (Interferon Beta-1a) in Healthy Volunteers [NCT01863069] | Phase 1 | 77 participants (Actual) | Interventional | 2001-01-31 | Completed |
| A Phase II, Single Arm, Multicenter Study of Nilotinib in Combination With Pegylated Interferon-α2b in Patients With Suboptimal Molecular Response or Stable Detectable Molecular Residual Disease After at Least Two Years of Imatinib Treatment (NordDutchCML [NCT01866553] | Phase 2 | 20 participants (Actual) | Interventional | 2013-04-30 | Terminated(stopped due to insufficient enrollment) |
| A Phase II Study of Interferon-Based Adjuvant Chemoradiation in Patients With Resected Pancreatic Adenocarcinoma [NCT00059826] | Phase 2 | 89 participants (Actual) | Interventional | 2003-03-31 | Completed |
| A Randomized, Single Center, Comparative Study to Evaluate the Efficacy and Safety of Silibinin (Legalon® SIL) in Combination With Ribavirin or With Peginterferon and Ribavirin, Versus Peginterferon and Ribavirin Based Standard of Care (SoC) in Treatment [NCT01871662] | Phase 2/Phase 3 | 0 participants (Actual) | Interventional | 2013-08-31 | Withdrawn |
| [NCT01872442] | Phase 2 | 0 participants | Interventional | 2013-10-15 | Completed |
| Interferon γ-Primed Mesenchymal Stromal Cells as Prophylaxis for Acute Graft v Host Disease After Allogeneic Hematopoietic Cell Transplantation for Patients With Hematologic Malignancies and Myelodysplasia [NCT04328714] | Phase 1 | 45 participants (Anticipated) | Interventional | 2021-12-02 | Suspended(stopped due to Study is suspended pending renovation and reopening of the facility manufacturing the study product.) |
| An Clinic Trial of Recombinant Human Interferon Alpha Nasal Drops to Prevent Coronavirus Disease 2019 in Medical Staff in Epidemic Area [NCT04320238] | Phase 3 | 2,944 participants (Anticipated) | Interventional | 2020-01-21 | Recruiting |
| A Pragmatic Trial to Evaluate the Intermediate-term Effects of Early, Aggressive Versus Escalation Therapy in People With Multiple Sclerosis [NCT03500328] | | 900 participants (Anticipated) | Interventional | 2018-05-02 | Recruiting |
| A Phase II Study Of Autologous Tumor/DC Vaccine (DC Vaccine) Combined With Interleukin-2 (IL-2) And Interferon-α-2a (IFNα-2a) In Patients With Metastatic Renal Cell Carcinoma (RCC) [NCT00085436] | Phase 2 | 18 participants (Actual) | Interventional | 2003-12-31 | Completed |
| A Phase II Study Of Peg-Intron, GM-CSF And Thalidomide In Metastatic Renal Cell Carcinoma [NCT00090870] | Phase 2 | 10 participants (Actual) | Interventional | 2002-04-30 | Terminated(stopped due to Pharmaceutical collaborator pulled funding.) |
| A RANDOMISED STUDY OF OBSERVATION VERSUS ADJUVANT LOW DOSE EXTENDED DURATION INTERFERON ALPHA-2A IN COMPLETELY RESECTED HIGH RISK MALIGNANT MELANOMA [NCT00002892] | Phase 3 | 1,000 participants (Anticipated) | Interventional | 1995-10-31 | Completed |
| Cytokine-Based Immunotherapy Following High-Dose Chemotherapy and Autologous Stem Cell Transplantation [NCT00003408] | Phase 2 | 40 participants (Anticipated) | Interventional | 1998-04-30 | Completed |
| HBsAg Loss/Seroconversion in Inactive Chronic Hepatitis B Carriers Treated With Peginterferon Alpha-2a [NCT01471535] | | 20 participants (Actual) | Interventional | 2008-05-31 | Completed |
| Randomized, Comparative Phase II/III Study Between Treatment With CSF470 Vaccine (Allogeneic, Irradiated) Plus BCG and MOLGRAMOSTIN (rhGM-CSF) as Adjuvants and Interferon-alfa 2b (IFN-ALPHA), in Stages IIB, IIC and III Post Surgery Cutaneous Melanoma Pati [NCT01729663] | Phase 2/Phase 3 | 108 participants (Anticipated) | Interventional | 2009-04-30 | Recruiting |
| Study Assessing Cognitive Performance Plus Physical Activity in Patients With Relapsing-Remitting MS Under Treatment With Betaferon® [NCT01491100] | | 1,085 participants (Actual) | Observational | 2012-04-30 | Completed |
| A Randomized, Single-Blind, Crossover Study in Healthy Volunteers to Demonstrate the Bioequivalence of Interferon Beta-1a Manufactured by Two Different Processes [NCT01500408] | Phase 1 | 110 participants (Actual) | Interventional | 2012-01-31 | Completed |
| Interferon Gamma Administration in Leukocyte Adhesion Deficiency Type I [NCT00001905] | Phase 2 | 5 participants | Interventional | 1999-04-30 | Completed |
| A Randomized Discontinuation Trial to Determine the Clinical Benefit of Continuation of Sorafenib Following Disease Progression in Patients With Advanced Renal Cell Carcinoma [NCT00352859] | Phase 4 | 2 participants (Actual) | Interventional | 2006-08-31 | Terminated |
| International, Randomized, Multicenter, Phase IIIb Study in Patients With Relapsing-Remitting Multiple Sclerosis Comparing Over a Treatment Period of at Least 104 Weeks: 1. Double-Blinded Safety, Tolerability, and Efficacy of Betaseron/ Betaferon 250 µg ( [NCT00099502] | Phase 3 | 2,244 participants (Actual) | Interventional | 2003-11-30 | Completed |
| Prospective Two-week Open-label Application Experimental Randomized Single-center Non-interventional Study of the Drug Ingaron in Patients With a New Coronavirus Infection COVID-19 [NCT05386459] | | 36 participants (Actual) | Observational | 2020-04-21 | Completed |
| Open-Label, Multicenter, Observational, Phase IV Study to Evaluate the Adherence to Treatment With 250mcg (8MIU) IFNB-1b (Betaseron®) Given Subcutaneous Every Other Day Over a Period of up to 12 Months in Patients With a First Clinical Demyelinating Event [NCT00461396] | | 104 participants (Actual) | Observational | 2007-05-31 | Completed |
| A Multi-centre, Double Blind, Randomised, Placebo Controlled, Parallel Group Study Investigating Simvastatin as an Add-on Treatment IM Administered Interferon-beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis [NCT00492765] | Phase 4 | 380 participants (Actual) | Interventional | 2006-02-28 | Completed |
| A Multi-Centre, Open Label Study to Investigate the Recovery of IFN-beta Efficacy in Relapsing-Remitting Multiple Sclerosis Patients With Neutralising IFN-beta Antibodies and Reduced Bioavailability [NCT00493116] | Phase 4 | 20 participants (Actual) | Interventional | 2003-10-31 | Completed |
| Optimizing IFN Beta - 1B Dose [NCT00473213] | Phase 3 | 217 participants (Actual) | Interventional | 1999-09-30 | Completed |
| Multicentric, Controlled and Randomised Open Clinical Trial Investigating the Efficacy and Safety of Dose Adaptation of Ribavirin Using Pharmacologic Measures of Ribavirin Exposition During Combination Peginterferon Alfa-2 and Ribavirin Treatment in Naive [NCT00485342] | Phase 3 | 236 participants (Anticipated) | Interventional | 2006-04-30 | Recruiting |
| A Randomized Trial Comparing a Short Course Versus Standard Treatment in Patients With Chronic Hepatitis C Virus Infection [NCT00502970] | Phase 4 | 150 participants (Actual) | Interventional | 2004-05-31 | Completed |
| Adjuvant Low-dose Interleukin-2 (IL2) Plus Interferone-alpha (IFN) in Operable Renal Cell Cancer (RCC). Phase III, Randomized, Multicenter Trial of the Italian Oncology Group for Clinical Research (GOIRC). [NCT00502034] | Phase 3 | 310 participants (Actual) | Interventional | 1994-07-31 | Completed |
| A Study of Pegylated Alfa Interferon, Sunitinib and Tarceva in Patients With Metastatic Renal Cell Carcinoma [NCT00522249] | Phase 1/Phase 2 | 10 participants (Actual) | Interventional | 2007-05-31 | Terminated(stopped due to PI decision) |
| A Phase III Prospective Randomized Comparison of Imatinib at a Dose of 400mg in Combination With Peg-Interferon-alpha2a (Peg-IFNa2a) or Cytarabine (Ara-C)Versus Imatinib at a Dose of 600mg Versus Imatinib a Dose of 400mg for Previously Untreated Chronic M [NCT00219739] | Phase 3 | 789 participants (Actual) | Interventional | 2003-09-30 | Completed |
| Evaluation of Birdshot RETINE CHOROIDOPATHY Treatment by Either Steroid or Interferon alpha2a [NCT00508040] | Phase 2 | 58 participants (Actual) | Interventional | 2007-09-30 | Completed |
| Effectiveness and Side Effects of Pegylated Interferon Alpha-2a (Pegaferon®) Plus Ribavirin in the Patients With Chronic Hepatitis C [NCT00527540] | Phase 3 | 60 participants (Anticipated) | Interventional | 2007-02-28 | Completed |
| Retrospective Study to Evaluate the Impact of Using Interferon (Pegylated or Not) in the Treatment of Patients With Chronic Hepatitis C in Brazil (DECISION) [NCT01280656] | | 660 participants (Actual) | Observational | 2010-01-31 | Completed |
| Evaluation of the Correlation Between the MS Functional Composite Index and Two Quality of Life Scales (MS54 and AMS Quality of Life) in Relapsing MS Patients Treated With Interferon Beta-1a (AVONEX®) [NCT00534261] | Phase 4 | 284 participants (Actual) | Interventional | 1999-11-30 | Completed |
| A Phase I Trial of Monoclonal Antibody HGS-ETR2 (Lexatumumab) With or Without Interferon Gamma in Patients With Refractory Pediatric Solid Tumors [NCT00428272] | Phase 1 | 30 participants (Actual) | Interventional | 2006-12-04 | Terminated |
| [NCT00466219] | Phase 3 | 25 participants | Interventional | 2002-05-31 | Completed |
| A 2 Year, Double-blind, Randomized, Multicenter, Active-controlled Core Phase to Evaluate Safety & Efficacy of Daily Fingolimod vs Weekly Interferon β-1a im in Pediatric Patients With Multiple Sclerosis and 5 Year Fingolimod Extension Phase [NCT01892722] | Phase 3 | 220 participants (Anticipated) | Interventional | 2013-07-26 | Recruiting |
| Four Arms, Multicenter, Open Label Study of Tailored Regimens With Peginterferon Plus Ribavirin for Genotype 2 Chronic Hepatitis C [NCT00540345] | Phase 4 | 300 participants (Actual) | Interventional | 2006-10-31 | Completed |
| An Open-label Randomized Controlled Trial on Interferon β-1b and Remdesivir Combination Versus Remdesivir as Treatment for COVID-19 Infection [NCT04647695] | Phase 2 | 100 participants (Anticipated) | Interventional | 2020-11-20 | Recruiting |
| A Multicentre, Randomized Controlled Trial in HBsAg Seroclearance After Receiving Combined Therapy of Peginterferon and Tenofovir in Nucleos(t)Ide Analogue-treated Patients With HBV Related Liver Fibrosis. [NCT04640129] | Phase 4 | 272 participants (Anticipated) | Interventional | 2020-11-30 | Not yet recruiting |
| Effect and Safety of Adding Metformin to the Standard Treatment of Hepatitis C on Sustained Viral Response [NCT00560690] | Phase 4 | 140 participants (Actual) | Interventional | 2007-12-31 | Completed |
| A Phase II Trial to Assess the Activity of TroVax® Alone vs. TroVax® Plus Interferon Alfa (IFN-α) on Patients With Advanced or Metastatic Renal Cell Cancer [NCT00445523] | Phase 2 | 28 participants (Actual) | Interventional | 2006-05-31 | Completed |
| Phase III Randomized Study of Four Weeks High Dose IFN-2b in StageT3-T4 or N1 (Microscopic) Melanoma [NCT00447356] | Phase 3 | 0 participants (Actual) | Interventional | 2000-01-31 | Withdrawn(stopped due to There were no patient enrolled in this study at this site) |
| Subcutaneous Continuous Infusion of Interferon Alfa-2b and Ribavirin in Hepatitis C Genotype 1 Nonresponders [NCT00624325] | Phase 2/Phase 3 | 30 participants (Actual) | Interventional | 2007-07-31 | Completed |
| An Open-Label, Pilot, Randomized, Multi-Center Study to Compare Efficacy and Safety of Tenofovir Monotherapy Alone With Tenofovir Monotherapy Followed by Concurrent Combination of Pegylated Interferon-Alpha-2b and Tenofovir or Tenofovir Monotherapy Follow [NCT01727271] | Phase 4 | 0 participants (Actual) | Interventional | 2013-08-31 | Withdrawn |
| International, Multicenter, Randomized, Double Blind, Active-controlled, Parallel-group Phase III Study of Narlaprevir/Ritonavir and Pegylated Interferon/Ribavirin in 2 Patient Populations - naïve and Treatment Failure Patients With Genotype 1 Chronic Hep [NCT03833362] | Phase 3 | 420 participants (Actual) | Interventional | 2014-05-07 | Completed |
| The SIM-SOF Trial: A Randomized Trial Comparing Simeprevir-Sofosbuvir Versus Peginterferon/Ribavirin/Sofosbuvir for the Treatment of Chronic Hepatitis C Genotype-1a-infected Patients With Cirrhosis [NCT02168361] | Phase 4 | 93 participants (Actual) | Interventional | 2013-12-31 | Completed |
| A Randomized Phase III Trial of Hyperthermic Isolated Limb Perfusion With Melphalan, Tumor Necrosis Factor, and Interferon-Gamma in Patients With Locally Advanced Extremity Melanoma [NCT00001296] | Phase 3 | 122 participants | Interventional | 1992-02-29 | Completed |
| Phase III Randomized Double-Blind Placebo Controlled Study To Evaluate the Safety and Efficacy of Betaseron in AIDS and Advanced ARC Patients Receiving a Reduced-Dose AZT Regimen [NCT00002238] | Phase 3 | 0 participants | Interventional | | Completed |
| The Treatment of Multiple Myeloma Utilizing VBMCP Chemotherapy Alternating With High-Dose Cyclophosphamide and Alpha2b-Interferon Versus VBMCP: A Phase III Study for Previously Untreated Multiple Myeloma [NCT00002556] | Phase 3 | 312 participants (Actual) | Interventional | 1994-07-31 | Completed |
| PHASE II STUDY OF SIMULTANEOUS HOMOHARRINGTONINE (NSC 141633) AND ALPHA INTERFERON (IFN-A) THERAPY IN CHRONIC MYELOGENOUS LEUKEMIA (CML) [NCT00002574] | Phase 2 | 87 participants (Actual) | Interventional | 1994-09-30 | Completed |
| Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate, Indomethacin and Recombinant Human Interferon-Gamma in Advanced Colorectal Cancer [NCT00002796] | Phase 1/Phase 2 | 46 participants (Actual) | Interventional | 1997-05-31 | Terminated(stopped due to Administratively complete.) |
| Randomized Trial of Autologous GVHD for Refractory Lymphoma [NCT00003414] | Phase 3 | 50 participants (Anticipated) | Interventional | 1997-10-31 | Completed |
| A European Randomized Multicenter Study of Interferon Alfa-2b Versus No Treatment After Intensive Therapy and Autologous Hematopoietic Stem Cell Transplantation for Relapsing Lymphoma Patients (Non-Hodgkin Lymphomas and Hodgkin's Disease) [NCT00003924] | Phase 3 | 360 participants (Anticipated) | Interventional | 1995-10-31 | Active, not recruiting |
| Intraperitoneal (IP) Autologous Therapeutic Tumor Vaccine AUT-OV-ALVAC-h.B7.1 Plus IP rIFN-gamma for Patients With Ovarian Cancer. A Pilot Study [NCT00004032] | Phase 1 | 12 participants (Actual) | Interventional | 1997-10-31 | Completed |
| A National Phase II Trial of Intron (Interferon-alfa 2b) Plus BCG for Treatment of Superficial Bladder Cancer [NCT00004122] | Phase 2 | 0 participants | Interventional | 1999-07-31 | Completed |
| Effectiveness and Tolerability of Hepatitis C Treatment in HIV Co-infected Patients in Routine Care Services in Asia: A Pilot Model of Care Project [NCT01838772] | Phase 4 | 188 participants (Actual) | Interventional | 2013-12-31 | Completed |
| Open-label Early Phase 2 Study With a Single Arm of Interferon Gamma-1b Treatment of Osteopetrosis [NCT02666768] | Phase 2 | 5 participants (Actual) | Interventional | 2016-02-22 | Completed |
| Phase 1/2 Study of Human Menstrual Blood-derived Mesenchymal Stem Cells Transplantation for the Evaluation of the Efficacy and Safety in Patients With Liver Cirrhosis [NCT01483248] | Phase 1/Phase 2 | 50 participants (Anticipated) | Interventional | 2010-10-31 | Enrolling by invitation |
| Effect of Infliximab in Hepatitis-C Genotype 1 Naïve Patients With High TNF-alpha on the Efficacy of Pegylated Interferon Alfa-2b/Ribavirin Therapy [NCT00237484] | Phase 3 | 89 participants (Actual) | Interventional | 2005-07-18 | Completed |
| An Open-Label Study of the Safety of Subcutaneous Recombinant Interferon Gamma-1b in Patients With Idiopathic Pulmonary Fibrosis [NCT00076635] | Phase 3 | 91 participants (Actual) | Interventional | 2003-11-30 | Terminated(stopped due to program discontinued based on GIPF-007 results) |
| Phase IV Study of Treatment of Acute Hepatitis C With Pegylated Interferon [NCT00241618] | Phase 4 | 180 participants | Interventional | 2002-01-31 | Completed |
| A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Determine the Safety and Efficacy of AVONEX When Used in Subjects With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) [NCT00099489] | Phase 2 | 67 participants | Interventional | 2004-02-29 | Completed |
| A Phase I Trial of Peginterferon Alfa-2b (PEG-Intron) for Plexiform Neurofibromas [NCT00253474] | Phase 1 | 36 participants (Anticipated) | Interventional | 2005-09-30 | Completed |
| An Open-Label, Randomized Study to Determine the Impact of Antiretroviral Treatment in HCV/HIV-Coinfected Subjects With High CD4+ Cell Count on the Efficacy of Hepatitis C Treatment With Pegylated Interferon Alfa-2A and Ribavirin [NCT00100581] | | 2 participants (Actual) | Interventional | | Completed |
| A Phase II/III Study of Immunomodulation After High Dose Myeloablative Therapy With Autologous Stem Cell Rescue for Refractory/Relapsed Hodgkin Disease [NCT00070187] | Phase 2/Phase 3 | 24 participants (Actual) | Interventional | 2003-11-30 | Completed |
| Adjuvant α-Interferon Treatment After Resection of Hepatocellular Carcinoma in HCV-Related Cirrhosis: a Randomized Trial on Prevention of Cancer Recurrence [NCT00273247] | Phase 3 | 150 participants | Interventional | 1998-06-30 | Completed |
| Randomized, Controlled Study of Buprenorphine and Methadone in Hepatitis C Patients in Need of Treatment [NCT00279565] | Phase 4 | 128 participants | Interventional | 2005-08-31 | Terminated(stopped due to The trial was terminated because of deviations from the protocol.) |
| A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of the Safety and Efficacy of Interferon Gamma-1b in Patients With Idiopathic Pulmonary Fibrosis (The INSPIRE Trial) [NCT00075998] | Phase 3 | 826 participants (Actual) | Interventional | 2003-12-31 | Terminated(stopped due to test drug showed lack of benefit at interim analysis) |
| A Multi-Center Phase II Study of Nonmyeloablative Conditioning With TBI and Fludarabine for HLA-Matched Related Hematopoietic Cell Transplantation for Treatment of Chronic Myeloid Leukemia in Chronic and Accelerated Phase [NCT00110058] | Phase 2 | 40 participants (Anticipated) | Interventional | 2005-02-28 | Completed |
| A Multicenter, Randomized, Controlled Trial of Combination Therapy for HBeAg Positive Chronic Hepatitis B: Comparing Thymosin Alpha 1 and Pegylated Interferon-alpha2a With Pegylated Interferon-alpha2a Alone. [NCT00291616] | Phase 4 | 52 participants (Actual) | Interventional | 2005-12-31 | Completed |
| A Phase I Clinical Trial of Repeated Dose Intrapleural Adenoviral-Mediated Interferon-beta (BG00001, Ad.hIFN-β for Pleural Malignancies [NCT00299962] | Phase 1 | 17 participants (Actual) | Interventional | 2006-03-31 | Completed |
| A Phase 3, Randomized, Open-Label Study of the Safety and Efficacy of Two Dose Levels of Interferon Alfacon-1 (Infergen, CIFN) Plus Ribavirin Administered Daily for 48 Weeks Versus No Treatment in Hepatitis C Infected Patients Who Are Nonresponders to Pre [NCT00086541] | Phase 3 | 515 participants (Actual) | Interventional | 2004-06-30 | Completed |
| A Phase II, Multicenter, Randomised, Double-blind, Placebo Controlled, Dose Finding Study of Subcutaneously Administered Interferon Beta-1a for Maintenance of Remission in Patients With Crohn's Disease [NCT00304252] | Phase 2 | 192 participants | Interventional | 2001-11-30 | Terminated(stopped due to Lack of Efficacy) |
| A Phase II Clinical Trial of a Timing/Schedule Optimized Combined-Modality Regimen: Cisplatin + Metronomic Low-Dose Interferon-α (IFN-α) Followed by Gemcitabine HCl (GEMZAR) in Combination With Mild, Fever-Range Whole-Body Hyperthermia (FR-WBH) in Patient [NCT00082862] | Phase 2 | 48 participants (Anticipated) | Interventional | 2002-07-31 | Recruiting |
| A Randomized, Phase IIb Clinical Trial to Evaluate the Safety and Antiviral Activity of NM283 and the Combination of Pegylated Interferon Plus NM283, in Patients With Chronic Hepatitis C Who Have Previously Failed to Respond to Standard Therapy [NCT00120861] | Phase 2 | 0 participants | Interventional | 2005-01-31 | Completed |
| Chronic Hepatitis C: Treatment of (Peg)Interferon Alpha - Ribavirin Non-Responders With Pegylated Interferon alpha2b, Ribavirin, AdoMet and Betaine [NCT00310336] | Phase 2/Phase 3 | 30 participants (Anticipated) | Interventional | 2006-08-31 | Completed |
| Combined Treatment With Capecitabine and Immunotherapy Versus Immunotherapy Alone in Advanced Renal Cell Carcinoma: a Prospective, Randomized, Multi-center phaseIII-Trial [NCT00311467] | Phase 3 | 172 participants (Actual) | Interventional | 2004-03-31 | Terminated(stopped due to no patient recruitment) |
| A Phase II Dose Escalation Study of Continuous Daily Subcutaneous Administration of Interferon Alpha-2b in Patients With Metastatic or Unresectable Clear Cell Renal Cell Carcinoma [NCT00293527] | Phase 2 | 0 participants (Actual) | Interventional | | Withdrawn(stopped due to Withdrawn in October 2006, no longer of interest) |
| A Pilot Safety Trial of STING-dependent Activators (STAVs) and Stimulated Dendritic Cells for Aggressive Relapsed/Refractory Leukemias [NCT05321940] | Phase 1 | 0 participants (Actual) | Interventional | 2023-11-30 | Withdrawn(stopped due to Investigator decision) |
| Pilot Open Label Clinical Trial Evaluating the Safety and Efficacy of Chemokine Modulation to Enhance the Effectiveness of Pembrolizumab in Patients With Metastatic Triple Negative Breast Cancer [NCT03599453] | Early Phase 1 | 8 participants (Actual) | Interventional | 2019-01-09 | Completed |
| A Study to Evaluate the Erythropoietic Response in Hepatitis C Virus (HCV) Patients Receiving Combination Ribavirin (RBV)/Interferon (IFN) Therapy or RBV/PEG IFN [NCT00328549] | Phase 2 | 105 participants (Actual) | Interventional | 2001-10-31 | Completed |
| A Phase I Study of EC90 With GPI-0100 Adjuvant Followed by EC17 With Cytokines (Interleukin-2 [IL-2] and Interferon-alpha [IFN-alpha]) in Patients With Refractory or Metastatic Cancer [NCT00329368] | Phase 1 | 13 participants (Actual) | Interventional | 2005-09-30 | Completed |
| Randomized, Double-Blind, Multicenter Study to Compare the Safety and Efficacy of Viramidine to Ribavirin in Treatment-Naive Patients With Chronic Hepatitis C [NCT00093093] | Phase 3 | 900 participants | Interventional | 2004-06-30 | Completed |
| A Phase II Trial of Belinostat as Consolidation Therapy With Zidovudine for Adult T-Cell Leukemia-Lymphoma [NCT02737046] | Phase 2 | 10 participants (Anticipated) | Interventional | 2016-12-12 | Recruiting |
| Multi-Center Trial to Evaluate the Efficacy and Safety of Structured Treatment Interruptions With or Without Pegylated Interferon Alpha for HIV-Infected Patients After Prolonged Viral Suppression (ANRS 105 INTERVAC) [NCT00125814] | Phase 3 | 200 participants | Interventional | 2001-12-31 | Terminated |
| A Multicenter, Randomized, Open-Label, Parallel-Group, Active-Controlled Study to Evaluate the Benefits of Switching Therapy (Glatiramer Acetate or Interferon Beta-1a) to Natalizumab in Subjects With Relapsing Remitting Multiple Sclerosis [NCT01058005] | Phase 3 | 84 participants (Actual) | Interventional | 2010-03-31 | Terminated(stopped due to Due to significantly slower than expected enrollment, the Sponsor decided to terminate the study.) |
| An Open-label, Single-arm, Roll-over Trial of Telaprevir in Combination With Pegylated Interferon Alfa-2a (Pegasys) and Ribavirin (Copegus) for Subjects From the Control Group of the VX- 950-TiDP24-C216 Trial Who Failed Therapy for Virologic Reasons [NCT01054573] | Phase 3 | 90 participants (Actual) | Interventional | 2010-04-30 | Completed |
| An Open-Label Trial of Pegylated Interferon Plus Ribavirin in Combination With CTS-1027 in HCV Null-Responders [NCT01051921] | Phase 2 | 67 participants (Actual) | Interventional | 2010-01-31 | Completed |
| A Pilot Study of Treatment With Pegylated Interferon-Alpha2a, Ribavirin and Insulin Sensitizer Pioglitazone of Insulin Resistance (With the Exception of Diabetes) in Hepatitis C Virus Infection (The INSPIRED HCV Study) [NCT00433069] | Phase 2 | 5 participants (Actual) | Interventional | 2007-01-31 | Completed |
| Pegylated Interferon Therapy for Acute Hepatitis C Infection in HIV-infected Patients [NCT00132210] | Phase 4 | 200 participants (Anticipated) | Interventional | 2002-09-30 | Completed |
| A Multicenter, Randomized, Double-blind, Controlled, Non-inferiority Phase III Clinical Trial of Recombinant Human Interferon Alpha-2b Gel (ZK-A03) in Treatment of Herpes Zoster Before and After the Alteration of the Active Ingredient Manufacturer [NCT05806918] | Phase 3 | 368 participants (Anticipated) | Interventional | 2023-04-01 | Not yet recruiting |
| Comparison of Bone Effects With Copaxone and Interferon in Multiple Sclerosis: A Pilot Study [NCT00490906] | | 60 participants (Actual) | Observational | 2007-06-30 | Completed |
| Phase I Evaluation of Sodium Stibogluconate in Combination With Interferon α-2b Followed by Cisplatin, Vinblastine and Dacarbazine for Patients With Melanoma or Malignancies Potentially Responsive to SSG and/or Interferons [NCT00498979] | Phase 1 | 22 participants (Actual) | Interventional | 2007-05-31 | Completed |
| A Phase II Study Evaluating the Efficacy and Tolerance of Combination Therapy of Imatinib Mesylate (IM) +-2A Interféron for Chronic Phase CML Patients Resistant or Refractory to IM Used as Single Therapy for at Least One Year [NCT00146913] | Phase 2 | 30 participants | Interventional | 2004-03-31 | Active, not recruiting |
| Phase 4 Comparative Study of Pegasys vs Peg-Intron for Treatment of Chronic Hepatitis C Genotype 4 [NCT00502099] | Phase 4 | 217 participants (Actual) | Interventional | 2006-01-31 | Completed |
| Pilot Study on Interferon Gamma in Association With Peg-Interferon Alpha 2a and Ribavirin Among Patients With a Chronic Hepatitis C and Non Responders to the Association of Peg-Interferon Alpha 2b or 2a and Ribavirin ANRS HC16 Gammatri [NCT00148863] | Phase 2 | 65 participants | Interventional | 2004-06-30 | Completed |
| Randomized Phase II Trial of Either 5-Fluorouracil, Recombinant Alfa-2a-Interferon and Intravenous Hydroxyurea With Filgrastim Support (FHIG) or Doxorubicin/Docetaxel (Dd) in Patients With Advanced Gastric Cancer [NCT00003172] | Phase 2 | 0 participants | Interventional | 1997-12-31 | Completed |
| OUTPATIENT SUBCUTANEOUS IL-2 AND ALPHA INTERFERON IN THE MANAGEMENT OF METASTATIC CANCER [NCT00002504] | Phase 2 | 0 participants | Interventional | 1992-08-31 | Completed |
| Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin Versus Pegylated Interferon Alfa-2a Alone for Treatment-naïve Hemodialysis Patients With Chronic Hepatitis C [NCT00491244] | Phase 4 | 377 participants (Actual) | Interventional | 2007-06-30 | Completed |
| Efficacy and Safety of Umifenovir as an Adjuvant Therapy Compared to the Control Therapeutic Regiment of Interferon Beta 1a, Lopinavir / Ritonavir and a Single Dose of Hydroxychloroquine in Moderate to Severe COVID-19: A Randomized, Double-Blind, Placebo- [NCT04350684] | Phase 4 | 40 participants (Anticipated) | Interventional | 2020-04-15 | Enrolling by invitation |
| A Greek Observational Study on Relapse Rate and Sustained Virological Response in Naive CHC Patients, Treated With Pegylated Interferon Alpha-2b and Ribavirin in Daily Clinical Practice [NCT00724464] | | 332 participants (Actual) | Observational | 2007-12-31 | Completed |
| Study to Investigate the Immune Response to Influenza Vaccine in Patients With Multiple Sclerosis on Teriflunomide Treatment and Using a Population of Patients With Multiple Sclerosis as a Reference [NCT01403376] | Phase 2 | 128 participants (Actual) | Interventional | 2011-09-30 | Completed |
| A Phase II Study of a-Interferon With Adriamycin, Bleomycin, Velban, and Dacarbazine (ABVD) for Patients With Hodgkin's Disease [NCT01404936] | Phase 2 | 35 participants (Actual) | Interventional | 1996-07-31 | Completed |
| Phase III Study of Recombinant Human Interferon-alpha2a Versus Cyclosporin A for the Treatment of Ocular Behcet's Disease - a National,Randomised, Single-masked Controlled Trial (INCYTOB) [NCT00167583] | Phase 3 | 37 participants (Actual) | Interventional | 2004-11-30 | Completed |
| Phase II Trial of Concurrent Administration of Intravesical BCG & Interferon in the Treatment and Prevention of Recurrence of Superficial Transitional Carcinoma of the Urinary Bladder [NCT00539773] | | 10 participants (Actual) | Interventional | 2007-09-30 | Completed |
| A Phase 3, Randomized, Open-Label Study of the Safety and Efficacy of Two Dose Levels of Interferon Alfacon-1 (Infergen, CIFN) Plus Ribavirin Administered Daily for 48 Weeks Versus No Treatment in Hepatitis C Infected Patients Who Are Nonresponders to Pre [NCT00162734] | Phase 3 | 144 participants (Actual) | Interventional | 2005-02-28 | Completed |
| Phase II Study of Mild Whole Body Hyperthermia Combined With 5-Fluorouracil/Interferon-a/Liposomal Doxorubicin in Patients With Advanced Malignancy [NCT00178802] | Phase 2 | 24 participants (Anticipated) | Interventional | 1996-06-30 | Active, not recruiting |
| Antiviral & Antifibrotic Liver Therapy in HCV + Drinkers and Non-Drinkers [NCT00211848] | Phase 2 | 207 participants (Anticipated) | Interventional | 2000-06-30 | Completed |
| Pilot Study of Addition of IL-2 to Pegylated Interferon Alpha 2a and Ribavirin for the Treatment of Chronic Hepatitis C in HIV-HCV Coinfected Patients Non Responders to Three Months of Therapy With Pegylated Interferon Alpha 2a and Ribavirin. ANRS HC09 SE [NCT00196586] | Phase 2 | 75 participants | Interventional | 2003-04-30 | Completed |
| A Multi-Centered, Prospective, Randomized, Placebo-Controlled Clinical Trial for the Treatment of Significant Steatosis or NASH With Xenical Followed by Treatment of Hepatitis C (HCV) With PEG-Interferon Alpha-2a/Copegus [NCT00207311] | Phase 4 | 30 participants (Actual) | Interventional | 2005-08-31 | Completed |
| Phase II Study of Pegylated Interferon and Thalidomide in Pretreated Metastatic Malignant Melanoma [NCT00238329] | Phase 2 | 32 participants (Anticipated) | Interventional | 2001-01-31 | Completed |
| An Open Labelled, Active Controlled, Three Arm, Parallel- Group Study of the Safety and Efficacy of Renessans Administered Alone and in Combination With Standard Interferon Therapy in Patients Chronic HCV Hepatitis [NCT01463592] | Phase 3 | 90 participants (Actual) | Interventional | 2010-06-30 | Active, not recruiting |
| COPE-HCV: Continuous Interferon Delivery Via the Medtronic Paradigm Pump Infusion System Clinical Evaluation for Chronic HCV [NCT00919633] | Phase 2 | 116 participants (Actual) | Interventional | 2009-06-30 | Completed |
| Effects of Traditional Chinese Medicines (TCMs) on Patients With COVID-19 Infection: A Perspective, Open-labeled, Randomized, Controlled Trial [NCT04251871] | | 150 participants (Anticipated) | Interventional | 2020-01-22 | Recruiting |
| A Phase 2b Study of Daclatasvir in Combination With Peg-Interferon Alfa-2a and Ribavirin in Treatment Naive Subjects With Chronic Hepatitis C Genotype 1 and 4 Infection [NCT01125189] | Phase 2 | 558 participants (Actual) | Interventional | 2010-07-31 | Completed |
| An Extension Study to Protocol VIR-NCHR-01 to Assess the Antiretrovirological Properties of a Therapeutic HIV Vaccine Candidate Based on Recombinant Fowlpox Virus (rFPV) (ITV Extension Study) [NCT00332930] | Phase 1/Phase 2 | 35 participants | Interventional | 2002-09-30 | Completed |
| A Randomized, Double-blind, Placebo-controlled Study to Determine the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the FXR-agonist EYP001a in Chronically HBV Infected Subjects [NCT03272009] | Phase 1 | 73 participants (Actual) | Interventional | 2017-09-21 | Completed |
| A Swedish Multi-Centre, Prospective, Open Label Study: Safety of Avonex Treatment in Multiple Sclerosis Patients Who Are NAB Positive on Previous s.c Interferon Beta Therapy [NCT00493077] | Phase 4 | 3 participants (Actual) | Interventional | 2004-05-31 | Completed |
| Study of Treatment High Risk and/or Low Risk Acute Lymphoblastic leukémia(ALL) Adults Stage III [NCT00483132] | Phase 3 | 232 participants (Actual) | Interventional | 1994-09-30 | Completed |
| An Open Label,Phase 3 Study of Telaprevir in Combination With Peginterferon Alfa 2a (Pegasys®) and Ribavirin (Copegus®) in Subjects Coinfected With Genotype 1 Hepatitis C Virus and Human Immunodeficiency Virus Type 1(HCV/HIV-1) [NCT01467479] | Phase 3 | 185 participants (Actual) | Interventional | 2011-12-31 | Terminated(stopped due to It was decided by Sponsor on 13 January 2014 to terminate study early at primary efficacy endpoint as part of a decision to modify drug development plan.) |
| Open-Label, Phase 3b Study to Determine Efficacy and Safety of Telaprevir, Pegylated-Interferon-alfa-2a and Ribavirin in Hepatitis C Virus Treatment-Naïve and Treatment-Experienced Subjects With Genotype 1 Chronic Hepatitis C and Human Immunodeficiency Vi [NCT01513941] | Phase 3 | 163 participants (Actual) | Interventional | 2012-04-30 | Completed |
| 24 VS 48-WEEK TREATMENT WITH PEG-IFN ALPHA-2A IN PATIENTS WITH GENOTYPE 2/3 CHRONIC HEPATITIS C, RELAPSERS TO PEG-IFN + RIBAVIRIN TREATMENT. A RANDOMIZED CONTROLLED TRIAL [NCT01517308] | Phase 3 | 0 participants (Actual) | Interventional | 2012-05-31 | Withdrawn(stopped due to Time elapsed to require permissions and a recent paper showed a high efficacy of a 48-week regimen in this setting. It seems non-ethical to start this trial) |
| Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection. [NCT00000764] | Phase 1 | 98 participants | Interventional | | Completed |
| Double-Blind, Randomized, Placebo-Controlled Study of Low Dose Oral Interferon Alfa-n3 (Human Leukocyte Derived) in ARC Patients [NCT00002012] | | 45 participants | Interventional | | Completed |
| An Observational, Multi-Center, Cohort Study Evaluating the Antiviral Efficacy, Safety, and Tolerability in Korean Patients With Chronic Hepatitis B (CHB) Receiving Pegylated Interferon-alpha 2a (Pegasys®): TRACES STUDY [NCT01531166] | | 500 participants (Actual) | Observational | 2011-09-30 | Completed |
| Pilot Study of Interferon Alfa for Patients Who Have Received Cancer Vaccines [NCT02159482] | Phase 2 | 11 participants (Actual) | Interventional | 2005-11-30 | Terminated(stopped due to Low enrollment) |
| A Multicenter Clinical Trial of Recombinant Human Interferon Gamma (Ingaron) in Pulmonary Tuberculosis [NCT06118619] | | 350 participants (Anticipated) | Observational | 2022-06-01 | Recruiting |
| Combination Therapy With 9-(1,3-Dihydroxy-2-Propoxymethyl) Guanine (DHPG) and Interferon Beta for the Prevention of Relapse of Cytomegalovirus Retinitis in Patients With the Acquired Immunodeficiency Syndrome [NCT00002299] | | 0 participants | Interventional | | Completed |
| Marrow-Ablative Chemo-Radiotherapy and Autologous Stem Cell Transplantation Followed by Interferon-Alpha Maintenance Treatment Versus Interferon-Alpha Maintenance Treatment Alone After a Chemotherapy-Induced Remission in Patients With Stages III or IV Fol [NCT00003152] | Phase 3 | 469 participants (Anticipated) | Interventional | 1997-03-31 | Terminated(stopped due to low accrual) |
| Phase II Trials of CHOP Chemotherapy and Interferon Alpha or Rituximab Anti-CD20 Monoclonal Antibody as Initial Treatment of Patients With Stage III and IV High-Risk Indolent B-Cell Lymphoma and Intermediate Grade B-Cell Lymphoma [NCT00004039] | Phase 2 | 0 participants (Actual) | Interventional | 1998-06-30 | Withdrawn(stopped due to No patient accruals) |
| Randomised Multicentre Phase IV Study to Compare Glivec® (Imatinib Mesylate, STI571) in Monotherapy Versus Glivec® in Combination With Interferon Alpha at Low Doses in the Treatment of Newly-Diagnosed Chronic-Phase Chronic Myeloid Leukaemia [NCT00390897] | Phase 4 | 360 participants | Interventional | 2003-07-31 | Completed |
| Non-Interventional Study Evaluating The Safety and Efficacy In Patients Receiving New PegIntron Pen for Hepatitis C [NCT01340573] | | 3 participants (Actual) | Observational | 2007-03-31 | Terminated(stopped due to Terminated early due to low enrollment.) |
| A Randomized, Open-label, Multi-center, Phase 3, 2-arm Study Evaluating the Efficacy and Safety of Peg Interferon Alfa-2b Low-dose Maintenance Monotherapy Versus Standard Supportive Care in Patients With Cirrhotic Hepatitis C Co-infected With Human Immuno [NCT00381017] | Phase 3 | 0 participants (Actual) | Interventional | 2006-09-30 | Withdrawn(stopped due to Non-protocol feasibility) |
| A Phase I Study of AZT and Human Interferon Alpha (Recombinant Alpha-2A and Lymphoblastoid) in the Treatment of AIDS-Associated Kaposi's Sarcoma [NCT00000725] | Phase 1 | 56 participants | Interventional | | Completed |
| A Randomized, Phase IIb Clinical Trial to Evaluate the Safety and Antiviral Activity of the Combination of Pegylated Interferon Alfa Plus NM283 (Valopicitabine) in Treatment-Naive Patients With Chronic Hepatitis C [NCT00118768] | Phase 2 | 175 participants | Interventional | 2005-08-31 | Completed |
| An Open-Label, Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and the Antiviral Activity of NM283 When Administered Alone and in Combination With Pegylated Interferon Alfa 2b to Treatment-Naive Adults With Genotype-1 Chronic Hepatitis C [NCT00120835] | Phase 1/Phase 2 | 0 participants | Interventional | 2004-07-31 | Completed |
| A Phase II Study of Alpha Interferon (alphaIFN) In HIV-Related Malignancies - A Pediatric Oncology Group Wide Study [NCT00002621] | Phase 2 | 8 participants (Actual) | Interventional | 1994-12-31 | Completed |
| Triple Therapy With Peg-Interferon Alfa-2b/Ribavirin Plus Amantadine Compared to Standard Peg-Interferon Alfa-2b/Ribavirin for Previous HCV Non Responders ANRSHC03 BITRI [NCT00122629] | Phase 3 | 405 participants | Interventional | 2000-10-31 | Terminated |
| Phase II Trial of 2-Fluorouracil Recombinant Alpha-2a-Interferon and Intravenous Hydroxyurea With Filgrastim in Patients With Refractory GI Malignancies Grant Application Title: Parenteral Hydroxyurea: A Modulator in Pancreatic Cancer [NCT00019474] | Phase 2 | 60 participants (Actual) | Interventional | 1998-03-31 | Completed |
| Phase II Clinical Trial of Intra-lesional Administration of TG1042 (Adenovirus-Interferon-gamma) in Patients With Relapsing Primary Cutaneous B-Cell Lymphomas. [NCT00394693] | Phase 2 | 13 participants (Actual) | Interventional | 2006-11-30 | Completed |
| Phase II Trial Of Combined Resection, Intraperitoneal Chemotherapy, And Whole Abdominal Radiation For Treatment Of Peritoneal Mesothelioma [NCT00024271] | Phase 2 | 0 participants | Interventional | 2001-05-31 | Active, not recruiting |
| Randomized Multicenter Treatment Optimization Study In Chronic Myeloid Leukemia (CML) Interferon-a Vs. Allogeneic Stem Cell Transplantation Vs. High-Dose Chemotherapy Followed By Autografting And Interferon-a Maintainance In Early Chronic Phase [NCT00025402] | Phase 3 | 1,000 participants (Anticipated) | Interventional | 1997-07-31 | Active, not recruiting |
| Phase II Trial of Interleukin-12 (NSC #672423, IND #6798) Followed by Interferon Alfa-2B in Patients With Metastatic Malignant Melanoma [NCT00026143] | Phase 2 | 60 participants (Actual) | Interventional | 2001-10-31 | Completed |
| Interferon Alpha In Combination With Thalidomide In The Treatment Of Metastatic Renal Cell Carcinoma A Randomized Phase II Study [NCT00027664] | Phase 2 | 90 participants (Anticipated) | Interventional | 2001-02-28 | Active, not recruiting |
| Granulocyte-Macrophage Colony Stimulating Factor (Rhu-GM-CSF) and Autologous Bone Marrow Transplantation for Chronic Myeloid Leukemia [NCT00011934] | Phase 2 | 0 participants | Interventional | 1998-05-31 | Completed |
| A Phase II Study of Temozolomide (Temodar) and Peglated Interferon Alfa-2B (PEGIntron) in the Treatment of Advanced Melanoma [NCT00027742] | Phase 2 | 0 participants | Interventional | 2001-05-31 | Completed |
| Therapeutic Safety and Efficacy of Combination Treatment With REP 2139-Ca and Pegasys in Patients With Chronic Hepatitis B [NCT02726789] | Phase 2 | 5 participants (Actual) | Interventional | 2012-10-31 | Completed |
| Phase I/II Study of Recombinant Human Interferon-gamma (rIFN-gamma) in HIV-Infected Children [NCT00000761] | Phase 1 | 20 participants | Interventional | | Completed |
| Pilot Study on Efficacy and Tolerance of Peg-interferon Alpha-2a (Pegasys) Added to Tenofovir DF and Emtricitabine (Truvada) in AGHBe Positive HBV-HIV Co-infected Patients. ANRS HB 01 EMVIPEG. [NCT00391638] | Phase 2/Phase 3 | 56 participants (Actual) | Interventional | 2007-01-31 | Completed |
| An Open Label Study of the Safety and Efficacy of Combination Therapy With AVONEX and Bi-Monthly High Dose Intravenous Methotrexate With Leucovorin Rescue in the Treatment of Multiple Sclerosis [NCT00037102] | Phase 4 | 16 participants (Actual) | Interventional | 2001-07-31 | Completed |
| A Phase II Study of SCH 54031 (Peg Interferon Alpha-2B/PEG-Intron) in Subjects With Interferon-Refractory Chronic Myelogenous Leukemia [NCT00037882] | Phase 2 | 1 participants (Actual) | Interventional | 2001-02-28 | Terminated |
| A Randomized Multicenter Phase II Trial of Recombinant Tumor Necrosis Factor and Recombinant Human Interferon-gamma in Patients With AIDS Related Complex [NCT00001004] | Phase 2 | 30 participants | Interventional | | Completed |
| A Phase II Clinical And Biologic Study Of The Combination Of Low Dose Interferon-Alpha And Thalidomide (NSC #66847) For Patients With Relapsed Or Refractory Low-Grade Follicular Lymphoma [NCT00015912] | Phase 2 | 35 participants (Actual) | Interventional | 2001-07-31 | Terminated(stopped due to Administratively complete.) |
| Treatment of Mantle Cell Lymphomas at Advanced Stages: Prospective Randomized Comparison of Myeloablative Radiochemotherapy Followed by Blood Stem Cell Transplantation Versus Maintenance With Interferon Alpha in First Remission After Initial Cytoreductive [NCT00016887] | Phase 3 | 0 participants | Interventional | 2000-12-31 | Active, not recruiting |
| A Phase I/II Study of Interferon Gamma-1b by Subcutaneous Injection for the Treatment of Patients With Cystic Fibrosis [NCT00043342] | Phase 1/Phase 2 | 51 participants (Actual) | Interventional | 2002-04-30 | Completed |
| A Phase I Study of the Safety, Tolerability, and Antitumor Activity of Escalating Doses of Intravenous CCI-779 Given in Combination With Escalating Doses of Interferon-Alpha to Patients With Advanced Renal Cancer [NCT00045370] | Phase 1 | 0 participants | Interventional | 2002-04-30 | Completed |
| Interferon Gamma-1b in Combination With Chemotherapy (Carboplatin/Paclitaxel) for First Line Therapy of Advanced Ovarian or Primary Peritoneal Carcinoma. [NCT00047632] | Phase 3 | 847 participants (Actual) | Interventional | 2001-10-31 | Terminated(stopped due to futility) |
| A Randomized, Double-Blind, Three-Arm, Phase IIIb Study Comparing the Safety and Efficacy of Interferon Gamma-1b Alone, IFN-Gamma 1b With Azathioprine, and Azathioprine Alone in Patients With Idiopathic Pulmonary Fibrosis Receiving Prednisone [NCT00052039] | Phase 3 | 0 participants (Actual) | Interventional | 2002-04-30 | Terminated(stopped due to Study design changes were needed based on GIPF-001 results) |
| A Prospective, Randomized, Double-Blind, Multicenter Pilot Study Of The Safety And Efficacy Of Interferon Gamma- 1b (IFN-y 1b) Plus Voriconazole Versus Placebo Plus Voriconazole In The Treatment Of Invasive Aspergillosis And Other Filamentous Fungal Infec [NCT00059878] | Phase 2 | 0 participants | Interventional | 2003-08-31 | Completed |
| A Randomized Phase III Trial Of Interferon Alfa-2B Or Interferon Alfa-2B Plus Bevacizumab In Patients With Advanced Renal Carcinoma [NCT00072046] | Phase 3 | 732 participants (Actual) | Interventional | 2003-10-31 | Completed |
| A Phase II, Double-Blind, Placebo-Controlled Study to Determine the Safety and Efficacy of a Humanized Anti-Interferon-γ Monoclonal Antibody (HuZAF) Administered to Patients With Moderate to Severe Crohn's Disease [NCT00072943] | Phase 2 | 175 participants | Interventional | 2002-03-31 | Completed |
| A Phase II Open-Label Pilot Trial of the Antiretroviral Activity, Safety, and Tolerability of Pegylated Interferon Alfa-2A (40KD) [PegasysTM] in HIV-1 Infected Subjects [NCT00078442] | Phase 2 | 12 participants (Actual) | Interventional | 2006-05-31 | Completed |
| A Randomized Clinical Trial Using Fine Needle Aspiration For Evaluation of Hepatic Pharmacokinetics of MK-5172 in Participants With Chronic Hepatitis C [NCT01547312] | Phase 1 | 0 participants (Actual) | Interventional | 2012-05-31 | Withdrawn |
| Randomized Study for Patients With Follicular Lymphoma Needing Treatment [NCT00140569] | Phase 3 | 400 participants | Interventional | 1994-01-31 | Completed |
| A Randomised Trial of Lamivudine Plus Interferon Versus Lamivudine for the Treatment of HBeAg Positive Chronic Hepatitis B Virus (HBV) [NCT00140725] | Phase 3 | 160 participants | Interventional | 2000-04-30 | Completed |
| A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Phase II Study of the Safety and Antifungal Activity of Subcutaneous Recombinant Interferon-Gamma 1b (rIFN-Gamma 1b) in Conjunction With Standard Therapy in Patients With Acute Cryptococcal Men [NCT00012467] | Phase 2 | 60 participants | Interventional | 2000-01-31 | Completed |
| A Phase I/II Trial of Combination Therapy With 5-Fluorouracil, Interferon-an Interleukin-2, and Thalidomide for Metastatic, Advanced or Recurrent Renal Cell Carcinoma. [NCT00277017] | Phase 1/Phase 2 | 15 participants (Actual) | Interventional | 2000-09-30 | Completed |
| A Phase-I Study Of Cyclical Oral Administration Of Temozolomide In Combination With PEG12000-Interferon Alfa-2B In Patients With Refractory And/Or Advanced Solid Tumors [NCT00014261] | Phase 1 | 0 participants | Interventional | 2000-10-31 | Completed |
| A Randomized, Double-Blinded, Placebo-Controlled, Phase II Study of the Safety and Efficacy of Inhaled Interferon Gamma-1b With Antimycobacterial in Previously Treated or Moderate to Severe Pulmonary Mycobacterium Avium Complex (MAC) Infection [NCT00021567] | Phase 2 | 20 participants | Interventional | 2001-07-31 | Completed |
| Evaluation of Interferon Alpha-2b and Thalidomide in Patients With Disseminated Malignant Melanoma, Phase II [NCT00026520] | Phase 2 | 0 participants | Interventional | 2001-11-30 | Completed |
| Pilot Studies of Gamma Interferon Therapy for Chronic Hepatitis C [NCT00028275] | Phase 2 | 20 participants | Interventional | 2001-12-31 | Completed |
| A Phase I/II Study Of Interleukin-12-Primed Activated T Cells In Combination With 5FU, GM-CSF And Interferon Alfa-2b In Metastatic Renal Cell Carcinoma Or Colorectal Carcinoma [NCT00030342] | Phase 1/Phase 2 | 60 participants (Anticipated) | Interventional | 2001-11-30 | Completed |
| Phase II Trial Of Oral Bexarotene (Targretin) Combined With Interferon Alfa-2b (Intron-A) For Patients With Cutaneous T-Cell Lymphoma [NCT00030849] | Phase 2 | 0 participants | Interventional | 2001-10-31 | Completed |
| A Multi-center, Open Label, Two Part, Dose Escalation Study to Determine the Tolerability of Interferon-Beta Gene Transfer (BG00001) in the Treatment of Recurrent or Progressive Grade III and Grade IV Gliomas [NCT00031083] | Phase 1 | 12 participants | Interventional | 2002-04-02 | Completed |
| Phase I Evaluation of Interferon-alpha-1b in Solid Tumors, Lymphoma or Myeloma [NCT00276536] | Phase 1 | 35 participants (Actual) | Interventional | 2001-01-31 | Completed |
| Phase II Study of Interferon Alpha and Isotretinoin in Patients With T-Cell Malignancies [NCT00038376] | Phase 2 | 56 participants (Actual) | Interventional | 1990-05-08 | Completed |
| A Phase I-II Pilot Study to Assess the Safety and Efficacy of Combined Administration With Pegylated Interferon-alpha2a and the Histone Deacetylase Inhibitor (HDACi) Panobinostat for Reducing the Residual Reservoir of HIV-1 Infected Cells in cART-Treated [NCT02471430] | Phase 1/Phase 2 | 34 participants (Anticipated) | Interventional | 2016-05-31 | Active, not recruiting |
| Induction of Graft Versus Tumor Effect of Pegylated Interferon Alpha-2b for Patients With Relapsed Hematological Malignancies After Allogeneic Stem Cell Transplantation [NCT02634294] | Phase 2/Phase 3 | 30 participants (Actual) | Interventional | 2015-08-31 | Completed |
| A Phase II Study of Protracted Infusional 5-Fluorouracil Plus Alpha Interferon for Advanced Metastatic Carcinoid [NCT00002470] | Phase 2 | 0 participants | Interventional | 1990-09-30 | Completed |
| A Prospective, Randomised, Open-label Phase IIb Clinical Trial Assessing the Effect of Pegylated Interferon Alfa-2a (Pegasys®)180 μg Once Weekly for 48 Weeks in Addition to an Ongoing Nucelos(t)Ide Based Treatment on Quantitative HBsAg Levels in Patients [NCT01524679] | Phase 2 | 170 participants (Actual) | Interventional | 2012-08-31 | Completed |
| "Ingested Interferon-Alpha: Prolongation or Permanence of the Honeymoon Phase in Newly Diagnosed Diabetes Mellitus" [NCT00024518] | Phase 2 | 57 participants (Actual) | Interventional | 2001-09-30 | Completed |
| A Randomized Controlled Trial of Interferon-alpha, Interleukin-2 and 5-Fluorouracil vs. Interferon-alpha Alone in Patients With Advanced Renal Cell Carcinoma [NCT00053820] | Phase 3 | 670 participants (Anticipated) | Interventional | 2002-07-31 | Completed |
| Phase II Study Of Bevacizumab And PEG Interferon Alpha-2b (PEG Intron) In Patients With Metastatic, Or Unresectable Carcinoid Tumors [NCT00055809] | Phase 2 | 44 participants (Actual) | Interventional | 2003-01-31 | Completed |
| Phase I/II Study of the Safety of Subcutaneous Interferon Gamma-1b Combined With Rituximab in Patients With Low Grade/Follicular Non-Hodgkin's Lymphoma [NCT00057447] | Phase 1/Phase 2 | 24 participants (Actual) | Interventional | 2003-03-31 | Terminated(stopped due to administrative reasons) |
| Pharmacological Interactions Between Zidovudine and Ribavirin in HCV-HIV Co-Infected Patients Treated With Rebetron or Peg-Intron Plus Ribavirin [NCT00059358] | Phase 1/Phase 2 | 16 participants (Anticipated) | Interventional | 2001-09-30 | Completed |
| An Open Label Pilot Study of Induction Therapy With a Single High Dose Bolus of Intravenous Methotrexate With Leucovorin Rescue, Prior to Initiation of AVONEX® Treatment, in Patients Presenting With a First Acute Demyelinating Event: Comparison With CHAMP [NCT00037115] | Phase 4 | 0 participants (Actual) | Interventional | 2002-05-31 | Withdrawn(stopped due to Lack of funding) |
| Randomized, Multicenter, Open Label Study to Compare the Efficacy and Tolerability of Pegylated Interferon-alpha-2 (PEG-IFN) to 'Low-dose' Interferon-alpha-2a in Patients With Malignant Melanoma in Stages IIA (T3a) - IIIB (AJCC 2002) [NCT00204529] | Phase 3 | 901 participants (Actual) | Interventional | 2004-10-31 | Completed |
| A Long-term Follow up of Patients Enrolled in the Pivotal Study of Betaseron® (Interferon Beta 1b) in Relapsing-remitting Multiple Sclerosis [NCT00206635] | | 432 participants (Actual) | Observational | 2005-01-31 | Completed |
| Efficacy of Maintenance Therapy With Rituximab After Induction Chemotherapy (R-CHOP vs. R-FC) for Elderly Patients With Mantle Cell Lymphoma Not Suitable for Autologous Stem Cell Transplantation [NCT00209209] | Phase 3 | 570 participants (Anticipated) | Interventional | 2004-01-14 | Active, not recruiting |
| Phase II Trial Of Induction Therapy With EPOCH Chemotherapy And Maintenance Therapy With Combivir/Interferon ALPHA-2a For HTLV-1 Associated T-Cell Non-Hodgkin's Lymphoma [NCT00041327] | Phase 2 | 19 participants (Actual) | Interventional | 2002-10-31 | Completed |
| [NCT00216775] | | 50 participants (Actual) | Observational | 2004-12-31 | Completed |
| A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Safety and Efficacy of Inhaled Interferon Gamma-1b With Antimycobacterials in Previously Treated or Mod-to-Sev Pulmonary Mycobacterium Avium Complex Infection [NCT00043355] | Phase 2 | 100 participants (Actual) | Interventional | 2000-12-31 | Terminated(stopped due to Futility) |
| A Phase II Open Label Study to Determine Safety and Efficacy of Interferon-alpha in Combination With Imantinib Mesylate (Gleevec) in Patients With Chronic Phase Chronic Myelogenous Leukemia Who Have Not Achieved a Complete Cytogenetic Response to Gleevec [NCT00045422] | Phase 2 | 0 participants | Interventional | 2002-04-30 | Completed |
| Evaluation of a Multi-disciplinary Approach for the Treatment of Hepatitis C in IDUs (HI-LO Study) [NCT00399672] | | 370 participants (Actual) | Interventional | 2007-06-30 | Completed |
| A Randomized, Double-Blind, Placebo-Controlled, Phase III Study of the Safety and Efficacy of Subcutaneous Recombinant Interferon-Gamma 1b in Patients With Idiopathic Pulmonary Fibrosis [NCT00047645] | Phase 3 | 330 participants (Actual) | Interventional | 2000-04-30 | Completed |
| HEPMET-1: Evaluate the Feasibility, Mental Sideeffects and the Efficacy of Hepatitis C Treatment in a Methadone Maintenance Treated (MMT) Opioid Addicted Group. [NCT00147784] | Phase 3 | 10 participants (Anticipated) | Interventional | 2006-03-31 | Completed |
| Randomized Double Blind Trial Comparing the Efficacy of Prazosin Versus Placebo Associated With Peg-Interferon Alpha 2b and Ribavirin for Initial Treatment of Patients With Hepatitis C With Genotype 1 or 4 and Severe Fibrosis [NCT00148837] | Phase 2 | 112 participants (Actual) | Interventional | 2004-09-30 | Active, not recruiting |
| Safety and Tolerability of Oral Two-Doses Estroprogestins Associated With Interferon-Beta 1a in Patients With Relapsing-Remitting Multiple Sclerosis [NCT00151801] | Phase 2 | 200 participants | Interventional | 2002-05-31 | Recruiting |
| Modulation of Death Effector Expression By Short-Term Exposure to Low-Dose Interferon [NCT00082719] | Phase 1 | 33 participants (Actual) | Interventional | 2003-12-31 | Completed |
| Analysis of the Duration of Combination Therapy That is Necessary for HCV Genotype 1 Eradication [NCT00152581] | Phase 4 | 40 participants | Interventional | 2002-04-30 | Completed |
| Randomized Trial of Therapy of Early Phase Chronic Myelogenous Leukemia With High-Dose Imatinib Mesylate (Gleevec) Alone or in Combination With Peg-Alpha Interferon (PEG-Intron) and Sargramostim (GM-CSF) [NCT00050531] | Phase 3 | 94 participants (Actual) | Interventional | 2003-04-30 | Completed |
| An Open-Label Study of the Safety and Efficacy of Subcutaneous Recombinant Interferon Gamma-1b in Patients With Idiopathic Pulmonary Fibrosis. [NCT00052052] | Phase 2 | 210 participants (Actual) | Interventional | 2002-09-30 | Completed |
| Adjuvant Interleukin-2, Interferon-alpha and 5-Fluorouracil for Patients With High Risk of Relapse After Surgical Treatment for Renal Cell Carcinoma [NCT00053807] | Phase 3 | 96 participants (Actual) | Interventional | 1998-02-28 | Completed |
| Phase II Trial of PEG-Intron in Patients With Advanced Renal Cell Carcinoma [NCT00045279] | Phase 2 | 0 participants | Interventional | 2002-04-30 | Completed |
| Tacrolimus Monotherapy in OLT Recipients With HCV Under Preemptive Treatment With Interferon and Ribavirin [NCT00167557] | Phase 4 | 0 participants (Actual) | Interventional | 2005-01-31 | Withdrawn(stopped due to The PI left the institution.) |
| A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel Group Trial Investigating Methylprednisolone in Combination With Interferon-beta-1a for the Treatment of Patients With Relapsing-remitting Multiple Sclerosis [NCT00168766] | Phase 4 | 345 participants (Actual) | Interventional | 2003-01-31 | Completed |
| Treatment Optimization Trial in Chronic Myeloid Leukemia (CML) - Randomized Controlled Comparison of Imatinib vs. Imatinib/Interferon-alpha vs. Imatinib/Low-Dose AraC vs. Interferon-alpha Standard Therapy and Determination of the Role of Allografting in N [NCT00055874] | Phase 3 | 1,551 participants (Actual) | Interventional | 2002-06-30 | Completed |
| A Phase II Trial of 13-Cis Retinoic Acid, Alpha Interferon, Taxotere, and Estramustine (R.I.T.E.) for the Treatment of Hormone Refractory Prostate Cancer [NCT00176527] | Phase 2 | 40 participants (Anticipated) | Interventional | 2002-11-30 | Terminated(stopped due to accrual goal met) |
| A Phase II Trial of G3139 (Genasense) Anti-Bcl-2 Antisense Oligonucleotide Plus Alpha-Interferon in Metastatic Renal Cancer [NCT00059813] | Phase 2 | 41 participants (Anticipated) | Interventional | 2003-08-31 | Completed |
| A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Biology, and Clinical Effects of Interferon Gamma-1b Administered Subcutaneously to Patients With IPF Followed by an Open-Label Extension [NCT00047658] | Phase 2 | 32 participants (Actual) | Interventional | 2001-11-30 | Completed |
| Safety and Tolerability of Consensus Interferon-Alpha (CIFN) Plus Interferon Gamma-1b (IFN-γ 1b) With or Without Ribavirin (RBV) in the Treatment of Patients With Chronic Hepatitis C Who Are Non-Responders to PEG-IFN-a (2a or 2b) Plus RBV [NCT00084279] | Phase 2 | 81 participants (Actual) | Interventional | 2004-04-30 | Completed |
| Randomized, Multicenter Study for Adjuvant Treatment of Stage III Malignant Melanoma: Intermittent, High-Dose Intravenous Interferon Alpha-2b Versus Standard High-Dose Interferon Alpha-2b Therapy [NCT00226408] | Phase 3 | 600 participants | Interventional | 2003-11-30 | Recruiting |
| A Study on the Viral Kinetics of Different Regimens of Pegylated Interferon and Lamivudine Combination Therapy in HBeAg Positive Chronic Hepatitis B [NCT00226447] | Phase 2 | 30 participants | Interventional | 2002-12-31 | Completed |
| A Phase 1-2 Study for Stage IV Breast and HER2/Neu Positive Cancers to Evaluate the Safety and Efficacy of a Vaccine Using Whole Cells From the SVBR- 1-GM Cell Line Genetically Engineered To Produce Granulocyte- Macrophage Colony Stimulating Factor [NCT00095862] | Phase 1/Phase 2 | 24 participants (Anticipated) | Interventional | 2004-11-30 | Terminated |
| Phase II Trial of Capecitabine (Xeloda®) and Pegylated Interferon Alfa-2A(Pegasys®) for Recurrent or Progressive Brain Metastasis From Breast Carcinoma [NCT00227656] | Phase 2 | 2 participants (Actual) | Interventional | 2005-09-30 | Terminated(stopped due to Study slow to accrue.) |
| Phase II Trial of ZD1839 (IRESSA®) and Pegylated Interferon Alfa 2b (PEG-Intron™) in Unresectable or Metastatic Renal Cell Carcinoma [NCT00467077] | Phase 2 | 21 participants (Actual) | Interventional | 2004-09-30 | Terminated(stopped due to Protocol was closed due to slow accrual.) |
| Predictive Value of HBV pgRNA on Long-term Outcomes in Hepatitis B Patients Treated With Antiviral Therapy [NCT05965388] | | 5,000 participants (Anticipated) | Observational | 2023-12-01 | Not yet recruiting |
| The Florida Melanoma Trial: A Phase I/II Trial of Post-Operative Adjuvant Radiotherapy With Concurrent Interferon-Alfa in the Treatment of Advanced Stage III Melanoma: Study Site & Coordinating Center [NCT00005615] | Phase 1/Phase 2 | 24 participants (Actual) | Interventional | 1997-07-31 | Completed |
| Neuroprotection With Riluzole in Patients With Early Multiple Sclerosis [NCT00501943] | Phase 2 | 43 participants (Actual) | Interventional | 2006-07-31 | Completed |
| Phase I Study of TH1 Dendritic Cell Immunotherapy for the Treatment of Cutaneous Angiosarcoma [NCT05799612] | Phase 1 | 24 participants (Anticipated) | Interventional | 2023-09-30 | Not yet recruiting |
| Study to Evaluate Response Rates in Chronic Hepatitis C (CHC) Patients Genotype 1 With Insulin Resistance and to Assess Prolonged Treatment Duration in Late Virological Responders [NCT00493805] | Phase 4 | 59 participants (Actual) | Interventional | 2007-04-30 | Terminated(stopped due to Slow Enrollment) |
| Controlled High-risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance (CHAMPIONS10) [NCT00179478] | Phase 4 | 155 participants (Actual) | Interventional | 2001-02-28 | Completed |
| Pilot Phase I/II Study of the Evaluation of Interferon Gamma-1b Administered Topically for Macular Edema/Intraretinal Schisis Cysts in Rod-Cone Dystrophy (RCD) and Enhanced S-Cone Syndrome (ESCS) [NCT02338973] | Phase 1/Phase 2 | 4 participants (Actual) | Interventional | 2015-01-14 | Terminated |
| SWITCH OR ADD PEGYLATED-INTERFERON IN CHRONIC HEPATITIS B PATIENTS ON LONG TERM NUCLEOS(T)IDE THERAPY (SWAP TRIAL) [NCT01928511] | Phase 4 | 254 participants (Actual) | Interventional | 2014-01-31 | Completed |
| An Open-label Randomized Controlled Trial on Lopinavir/ Ritonavir, Ribavirin and Interferon Beta 1b Combination Versus Lopinavir/ Ritonavir Alone, as Treatment for 2019 Novel Coronavirus Infection [NCT04276688] | Phase 2 | 127 participants (Actual) | Interventional | 2020-02-10 | Completed |
| A Phase I/II Open-Label Study to Assess the Safety, Tolerability and Preliminary Efficacy of FP-1201 (Recombinant Human Interferon Beta) in the Treatment of Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome. [NCT00789685] | Phase 1/Phase 2 | 37 participants (Actual) | Interventional | 2009-02-28 | Completed |
| Pilot Study of IFN-alpha-2b Dose Reduction With Dose Optimization [NCT01460875] | | 34 participants (Actual) | Interventional | 2008-04-22 | Completed |
| Randomised Phase II Study of Postoperative Hepatic Arterial Infusion Chemotherapy (Interferon/Fluorouracil Versus Low-dose Cisplatin/Fluorouracil) for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus. [NCT01834963] | Phase 2 | 66 participants (Anticipated) | Interventional | 2013-03-31 | Recruiting |
| A Phase II, Multicenter, Open-label, Randomized, Comparator Controlled Study to Evaluate the Efficacy and Safety of Pegylated Interferon - α2b in the Treatment of Adult Patients Diagnosed With SARS-CoV2 (COVID-19) [NCT04480138] | Phase 2 | 7 participants (Actual) | Interventional | 2020-08-11 | Terminated(stopped due to Due to non availability of eligible subjects and slow recruitment) |
| Assessing Tolerability of Avonex Intramuscular Injections With a 25 Gauge Needle Versus 30 Gauge Needle [NCT01641120] | | 20 participants (Actual) | Interventional | 2012-05-31 | Completed |
| Compassionate Use Access to REP 2139-Mg for the Treatment of Chronic HBV Infection or Chronic HBV / HDV Co-infection [NCT05683548] | | 0 participants | Expanded Access | | Available |
| Phase II Randomized Controlled Trial of Pegylated Interferon Alpha-2b in Early Primary Myelofibrosis [NCT01758588] | Phase 2 | 8 participants (Actual) | Interventional | 2013-01-31 | Terminated(stopped due to This study was suspended due to insufficient subject accrual.) |
| Nivolumab in Combination With Cisplatin and 5-Fluorouracil as Induction Therapy in Children and Adults With EBV-positive Nasopharyngeal Carcinoma [NCT06019130] | Phase 2 | 57 participants (Anticipated) | Interventional | 2023-01-10 | Recruiting |
| Multicenter Interventional Phase IV Study for the Assessment of the Effects on Patient's Satisfaction of Plegridy (Pre-filled Pen) in Subjects With Relapsing-remitting Multiple Sclerosis Unsatisfied With Other Injectable Subcutaneous Interferons (PLATINUM [NCT02587065] | Phase 4 | 193 participants (Actual) | Interventional | 2016-02-03 | Completed |
| Study on Screening, Verification and Intervention of High-risk Patients With Liver Cancer [NCT05721300] | | 2,215 participants (Anticipated) | Interventional | 2023-02-10 | Recruiting |
| Treatment With Peginterferon Alfa-2a (40 KD) (PEGASYS®) of Chronic Hepatitis B Patients, Who Have Failed Anti-viral Treatment. A Pilot Study. [NCT00226382] | Phase 4 | 50 participants (Actual) | Interventional | 2005-01-31 | Completed |
| Phase IV Study of Long Term Peg-Intron for Patients Who Have Failed to Respond to Rebetron/Interferon With Advanced Fibrosis and Cirrhosis Secondary to Hepatitis C- The Copilot Trial [NCT00179413] | Phase 4 | 549 participants (Actual) | Interventional | 2000-01-15 | Completed |
| POST-OPERATIVE ADJUVANT INTERFERON-ALFA-2B (INTRON-A) TREATMENT AFTER RESECTION OF THICK PRIMARY MELANOMA AND/OR REGIONAL LYMPHNODE METASTASES 'INTERMEDIATE-HIGH DOSE' VS INTERMEDIATE-LOW DOSE' IFN-ALFA VS OBSERVATION: A 3-ARM MULTICENTER RANDOMIZED PHASE [NCT00002763] | Phase 3 | 1,000 participants (Anticipated) | Interventional | 1996-04-30 | Active, not recruiting |
| A Phase I-II Study of Interferon-gamma Plus Weekly Paclitaxel, Trastuzumab and Pertuzumab in Patients With HER-2 Positive Breast Cancer [NCT03112590] | Phase 1/Phase 2 | 51 participants (Actual) | Interventional | 2017-06-23 | Completed |
| Postoperative Adjuvant Therapy With Recombinant Interferon-Alpha Following Curative Resection of Hepatocellular Carcinoma: a Randomized Controlled Trial [NCT00234182] | Phase 1/Phase 2 | 84 participants | Interventional | 2000-01-31 | Completed |
| Non-interventional Safety Study to Investigate Pregnancy Outcomes in Female Patients Exposed to SC Peginterferon Beta-1a and IM Interferon Beta-1a Reported in a German Patient Support Program [NCT04655222] | | 470 participants (Actual) | Observational | 2021-04-30 | Completed |
| [NCT00239252] | Phase 3 | 0 participants | Interventional | | Completed |
| Efficacy and Safety of a Hansenula-derived Pegylated Interferon α2a (Reiferon Retard®) in Treatment of Patients With Chronic Hepatitis C Virus Infection: A National Multi-center Phase IV Open Label Non-Randomized Trial [NCT01649245] | Phase 4 | 5,000 participants (Anticipated) | Interventional | 2012-08-31 | Recruiting |
| Multicenter Phase 2 Study of Efficacy and Safety of Pegylated Interferon-alfa 2a in Polycythemia Vera Patients [NCT00241241] | Phase 2 | 40 participants | Interventional | 2004-09-30 | Completed |
| A Phase I Study of Low Dose Interleukin 2 (IL-2)Monotherapy, Followed by IL-2 Plus PEG-IFN/RBV In Chronic Hepatitis C Virus Genotype I Infection [NCT00277758] | Phase 1 | 18 participants (Actual) | Interventional | 2004-03-31 | Terminated(stopped due to Insufficient rate of volunteer accrual.) |
| A Multicentre Phase III Study of Interferon-beta-1a for the Treatment of Chronic Hepatitis C in Asian Subjects [NCT00249860] | Phase 3 | 257 participants (Actual) | Interventional | 2002-09-30 | Completed |
| Trial of Thalidomide, a- Interferon +/- Octreotide in Patients With Unresectable Hepatocellular Carcinoma [NCT00250796] | Phase 2 | 12 participants (Actual) | Interventional | 2000-09-30 | Completed |
| Rituximab (Mabthera®) as Single Agent and in Combination With Interferon Alfa-2a (Roferon-A®), a Phase-III Randomized Trial in Patients With Follicular or Other CD20+ Low-grade (Indolent) Lymphoma [NCT01609010] | Phase 3 | 313 participants (Actual) | Interventional | 2002-10-31 | Completed |
| Cytokines in the Treatment of Metastatic Renal Cell Carcinoma (MRCC): Intravenous Interleukin and Subcutaneous Interferon-α Versus Subcutaneous Interleukin and Interferon-α for Good Prognosis Patients [PERCY DUO] [NCT00416871] | Phase 3 | 220 participants (Anticipated) | Interventional | | Completed |
| Study of Parameters of Early Hepatitis C Virus Dynamics for Predicting the Outcome of Standard Interferon Therapy With Chinese Cohort [NCT01434212] | | 40 participants (Anticipated) | Observational | 2010-05-31 | Active, not recruiting |
| Effect of Cyclical Administration of Interferon β-1b in Multiple Sclerosis - Comparison With Normal Dose. [NCT00270816] | Phase 2/Phase 3 | 60 participants (Actual) | Interventional | 2005-11-30 | Completed |
| PERCY QUATTRO: Medroxyprogesterone, Interferon Alpha-2a, Interleukin 2 or Combination of Both Cytokines in Patients With Metastatic Renal Carcinoma of Intermediate Prognosis [NCT00291369] | Phase 3 | 456 participants | Interventional | 1999-12-31 | Completed |
| A Dose-Frequency Blinded, Multicenter, Extension Study to Determine the Long-Term Safety and Efficacy of PEGylated Interferon Beta-1a (BIIB017) in Subjects With Relapsing Multiple Sclerosis [NCT01332019] | Phase 3 | 1,077 participants (Actual) | Interventional | 2011-04-30 | Completed |
| A Pilot Safety and Tolerability Open-Label Study of Interferon Beta-1b in Combination With Tacrolimus in Patients Suffering From Multiple Sclerosis Who Have Failed Treatment With Approved Disease Modifying Agents [NCT00298662] | Phase 2 | 30 participants | Interventional | 2003-02-28 | Active, not recruiting |
| Phase II Study of Gamma Interferon (IFN-γ) Added to Bolus + Infusional 5-Fluorouracil (5-FU) and Leucovorin (LV) +/- Bevacizumab (BV) in Metastatic Colorectal Carcinoma [NCT00786643] | Phase 2 | 48 participants (Actual) | Interventional | 2006-02-28 | Completed |
| A Phase 4 Open-Label Pilot Study of the Safety and Tolerability of High Dosage of CIFN Plus RBV Administered Daily for 48 Weeks in HCV Genotype 1 Infected Patients Who Are Nonresponders to Prior Pegylated Interferon Alfa Plus RBV Therapy [NCT00266318] | Phase 4 | 40 participants | Interventional | 2005-12-31 | Completed |
| [NCT00297570] | Phase 3 | 90 participants (Anticipated) | Interventional | 2006-02-28 | Recruiting |
| Medroxyprogesterone, Interferon Alpha-2a, Interleukin 2 or Combination of Both Cytokines in Patients With Metastatic Renal Carcinoma of Intermediate Prognosis [PERCY QUATTRO] [NCT00416429] | Phase 3 | 456 participants (Anticipated) | Interventional | | Completed |
| Bevacizumab, Dacarbazine and Interferon Alfa-2a Combination as a First-Line Therapy in Patients With Locally Advancing or Metastatic Melanoma [NCT00308607] | Phase 2 | 27 participants (Actual) | Interventional | 2005-08-31 | Completed |
| A Phase II Trial of Interferon Alpha-1b (IFN Alpha-1b) in Patients With Metastatic Clear Cell Renal Carcinoma [NCT00278174] | Phase 2 | 7 participants (Actual) | Interventional | 2005-02-28 | Completed |
| Randomized Study for the Assessment of Nitazoxanide in the Treatment of Chronic Hepatitis C Genotype 4 [NCT01276756] | Phase 2/Phase 3 | 100 participants (Actual) | Interventional | 2010-12-31 | Completed |
| [NCT00323505] | Phase 2 | 0 participants | Interventional | 2001-03-31 | Completed |
| A Multicentre, Randomised, Double-blind, Placebo-controlled, Dose-finding Phase II Study of Subcutaneously Administered IFN-beta-1a in the Treatment of Patients With Moderately Active Ulcerative Colitis [NCT00303381] | Phase 2 | 194 participants (Actual) | Interventional | 2001-12-31 | Completed |
| A Randomized, Multicenter, phaseIIIB, Two Arm Study Evaluating the Tolerability of Peginterferon Alfa-2a Plus Ribavirin in Patients With Chronic Hepatitis C Genotype 1 Infection co-Infected With Human Immunodeficiency Virus Receiving HAART Versus Not Rece [NCT00296972] | Phase 3 | 100 participants | Interventional | 2005-07-31 | Terminated(stopped due to not funded) |
| Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With SCH54031 (PEG Interferon Alpha 2B/PEG Intron) and Low-Dose Cytosine Arabinoside (Ara-C) [NCT00303290] | Phase 1 | 76 participants (Actual) | Interventional | 2000-01-31 | Completed |
| 14 vs 24 Weeks HCV Treatment to Genotype 2/3 Patients With Rapid Virological Response [NCT00308048] | Phase 3 | 435 participants | Interventional | 2004-03-31 | Completed |
| A Prospectively Randomized Phase III Study on Adjuvant Chemotherapy and Adjuvant Chemo-Immunotherapy in Patients With Operated Colon Carcinoma Dukes C (Stage III; T1-4, N1-30, M0). [NCT00309530] | Phase 3 | 598 participants | Interventional | 1990-10-31 | Completed |
| Phase I Evaluation of Sodium Stibogluconate in Combination With Interferon α-2b for Solid Tumors, Lymphoma or Myeloma [NCT00311558] | Phase 1 | 18 participants (Actual) | Interventional | 2005-10-31 | Terminated |
| A Scandinavian, Randomized, Rater-blinded Study of Single and Double-dose Betaferon in Patients With Early Secondary Progressive Multiple Sclerosis [NCT00313976] | Phase 3 | 0 participants (Actual) | Interventional | | Withdrawn |
| A Monocentric, Randomized, Controlled Trial to Test the Efficacy of Interferon-beta in the Treatment of Disseminated Encephalomyelitis (ED)-Associated and Primary Intermediate Uveitis in Comparison to Standard Treatment (TEAM) [NCT00344253] | Phase 3 | 19 participants (Actual) | Interventional | 2006-03-31 | Completed |
| Phase 1/2 Study to Evaluate the Safety, Feasibility, and Efficacy of FP-1201 (Intravenous Interferon-Beta-1a) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy [NCT05936229] | Phase 1/Phase 2 | 24 participants (Anticipated) | Interventional | 2024-03-01 | Not yet recruiting |
| A Phase I Trial Testing Multiple Antigen-Engineered DC Followed by IFNa2b Boost for Immunization of HLA-Unrestricted Melanoma Patients [NCT01622933] | Phase 1 | 35 participants (Actual) | Interventional | 2012-06-30 | Completed |
| Observation Study of Different Optimized Therapy Method of Patients With Chronic Hepatitis B [NCT01623778] | | 67 participants (Actual) | Observational | 2009-01-31 | Completed |
| Inflammation, Stress and Social Behavior: Using Ecological Assessments and Model Systems to Enhance Relevance to Health Outcomes [NCT01625793] | | 0 participants (Actual) | Interventional | 2012-06-30 | Withdrawn(stopped due to New medication coming on the market, made study obsolete.) |
| Chemo-Immunotherapy: Observational Trial of Carboplatin-pegylated Liposomal Doxorubicin (PLD) or Doxorubicin Combination Chemotherapy With Tocilizumab, a Humanized Monoclonal Antibody Against the Human Interleukin-6 (IL-6) Receptor, and Pegylated Interfer [NCT01637532] | Phase 1/Phase 2 | 21 participants (Actual) | Interventional | 2011-02-28 | Completed |
| Eine Phase II Studie über Interferon Gamma 1b Zur Behandlung Der steroidrefraktären Bronchiolitis Obliterans Nach Allogener SZT [NCT01639261] | Phase 2 | 10 participants (Anticipated) | Interventional | 2012-07-31 | Active, not recruiting |
| Chemo-Immunotherapy, Gemcitabine With Pegylated Interferon Alpha-2b (Peg-Intron) With and Without p53 Synthetic Long Peptide (p53 SLP) Vaccine, for Patients With Platinum Resistant Ovarian Cancer CHIP Trial [NCT01639885] | Phase 1/Phase 2 | 15 participants (Actual) | Interventional | 2011-08-31 | Completed |
| Vitamin D in Addition to Pegylated Interferon and Ribavirin Compared to Pegylated Interferon and Ribavirin Alone in the Treatment of Chronic Hepatitis C Genotype 4. [NCT01655966] | Phase 3 | 80 participants (Anticipated) | Interventional | 2012-05-31 | Active, not recruiting |
| A Randomized, Open-Labeled Study to Evaluate the Efficacy and Safety of ABT-450/Ritonavir/ABT-267 and ABT-333 Co-administered With Ribavirin Compared to Telaprevir Co-administered With Pegylated Interferon a-2a and Ribavirin in Treatment-Experienced Adult [NCT01854528] | Phase 3 | 148 participants (Actual) | Interventional | 2013-06-30 | Completed |
| Phase III Randomized Study of Four Weeks of High Dose Interferon Alfa-2b in Stage T2bN0, T3a-bN0, T4a-bN0, and T1-4, N1a,2a (Microscopic) Melanoma [NCT00003641] | Phase 3 | 1,150 participants (Actual) | Interventional | 1999-03-25 | Active, not recruiting |
| CAMP-010: PHASE I/II STUDY OF IN VIVO PURGING FOLLOWED BY HIGH DOSE CHEMOTHERAPY, AUTOLOGOUS HEMATOPOIETIC STEM CELL INFUSION AND IMMUNOTHERAPY IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA [NCT00002761] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 1996-02-29 | Withdrawn(stopped due to PI left institution) |
| A Multicenter Trial of Adjuvant Interferon Alfa-2b for Melanoma Patients With Early Lymph Node Metastasis Detected by Lymphatic Mapping and Sentinel Lymph Node Biopsy [NCT00004196] | Phase 3 | 3,000 participants (Anticipated) | Interventional | 1999-10-31 | Completed |
| The Effect of Postoperative Interferon-alpha Treatment in Patients Underwent Curative Surgery for Hepatocellular Carcinoma With a Low miR-26 Expression: a Multi-center Randomized Clinical Trial. [NCT01681446] | Phase 3 | 296 participants (Anticipated) | Interventional | 2012-08-31 | Recruiting |
| A Pilot Phase II Two-Arm, Randomized Clinical Trial of Concomitant Immunotherapy (With Interferon-Alpha and Retinoic Acid) and Radiation Therapy for the Treatment of Advanced Cervical Cancer in India [NCT01276730] | Phase 2 | 209 participants (Actual) | Interventional | 2007-10-31 | Completed |
| Study to Evaluate Cellular Adoptive Immunotherapy Using Polyclonal Autologous CD8+ Antigen-Specific T Cells for Metastatic Merkel Cell Carcinoma in Combination With MHC Class I Up-Regulation and the Anti-PD-L1 Antibody Avelumab [NCT02584829] | Phase 1/Phase 2 | 8 participants (Actual) | Interventional | 2015-11-06 | Terminated(stopped due to Terminated due to loss in funding) |
| Natalizumab De-escalation to Interferon-beta-1b in Patients With Relapsing-remitting Multiple Sclerosis: A Swiss Multicenter Study Prospective, Controlled, Single-arm, Open-label, Multi-centre, Phase IV Study [NCT01701856] | Phase 4 | 5 participants (Actual) | Interventional | 2012-09-30 | Terminated(stopped due to Problems to recruit the needed number of patients in the planned time) |
| Assessment of Strategies for the Management of Flu-like Symptoms in MS Patients Commencing Treatment With Betaferon® [NCT01706055] | | 629 participants (Actual) | Observational | 2012-09-30 | Completed |
| A Phase II Study Evaluating RNS60 Compared to Interferon Beta-1a (Avonex) for the Treatment of Relapsing Remitting Multiple Sclerosis [NCT01714089] | Phase 2 | 0 participants (Actual) | Interventional | | Withdrawn |
| An Open-Label Re-Treatment Study With PegInterferon Alfa-2a, Ribavirin and BMS-790052 With or Without BMS-650032 for Subjects With Chronic Hepatitis C [NCT01428063] | Phase 2 | 276 participants (Actual) | Interventional | 2011-09-30 | Completed |
| A MULTICENTER, PROSPECTIVE, OBSERVATIONAL, NON-INTERVENTIONAL COHORT STUDY IN CHINESE SUBJECTS WITH HBeAg NEGATIVE CHRONIC HEPATITIS B (CHB) RECEIVING THERAPY WITH PEGINTERFERON ALFA [NCT01730508] | | 978 participants (Actual) | Observational | 2012-11-20 | Completed |
| Is Hepcidin a Possible Contributor to Impaired Iron Mobilization and Anaemia in Hepatitis C Patients Treated With Pegylated Interferon Alpha and Ribavirin Therapy? A Pilot Study [NCT01726400] | | 15 participants (Actual) | Observational | 2012-12-31 | Completed |
| Treatment and Natural History Study of Lymphomatoid Granulomatosis [NCT00001379] | Phase 2 | 105 participants (Anticipated) | Interventional | 1995-05-05 | Recruiting |
| Study of Parameters of Early Hepatitis C Virus Dynamics for Predicting the Outcome of Standard Interferon Therapy With Chinese Cohort (Second Phase) [NCT01760148] | | 300 participants (Anticipated) | Observational | 2012-07-31 | Recruiting |
| BETASLEEP - SLEEP Quality and Functional Health Status, Fatigue, Comorbidities and Therapeutic Algorithms Among BETAferon® Treated MS Patients [NCT01766063] | | 138 participants (Actual) | Observational | 2012-12-06 | Completed |
| HBsAg Decline and HBeAg Seroconversion Following 48 Weeks Peg-interferon-α Treatment in Patients With e Antigen Positive Chronic Hepatitis B After Nucleoside Analogue Maintenance Therapy Compared to Continuing Nucleoside Analogue Treatment [NCT01769833] | Phase 3 | 144 participants (Anticipated) | Interventional | 2013-05-31 | Active, not recruiting |
| An Expanded Access Phase 2 Study of Sofosbuvir With Ribavirin and With or Without Pegylated Interferon for 24 Weeks in Subjects Who Have Undergone Liver Transplantation and Who Have Aggressive, Recurrent Hepatitis C Infection [NCT01779518] | | 0 participants | Expanded Access | | Approved for marketing |
| A Phase II Randomized Study of Imatinib Versus High Dose Interferon as Adjuvant Therapy in KIT-mutated Patients With Resected Melanoma [NCT01782508] | Phase 2 | 40 participants (Anticipated) | Interventional | 2012-08-31 | Recruiting |
| Pilot Single-center Open Study of the Effect of Ingaron on the Efficacy and Resistance to Antibiotics in Antibacterial Therapy in Patients With Community-acquired Pneumonia [NCT05395702] | | 114 participants (Actual) | Interventional | 2017-05-12 | Completed |
| Randomized Trial of 24 or 48 Weeks of Peginterferon Alfa-2a Plus Ribavirin for Chronic Hepatitis C Virus Genotype 1-infected Patients in Taiwan [NCT00495131] | Phase 4 | 308 participants (Actual) | Interventional | 2006-06-30 | Completed |
| a Multi-sites, Randomized, Parallel, Controlled Clinical Study to Evaluated the Efficacy and Safety of Recombinant Human Interferon Alpha-2b Gel (Yallaferon®) in HPV Infection [NCT01824992] | Phase 2/Phase 3 | 325 participants (Actual) | Interventional | 2011-03-31 | Completed |
| Pharmacovigilance Study of the Interferon α 2b Produced by Bio-Manguinhos / Fiocruz and Used by Genotype 2/3 Chronic Hepatitis C Patients (Estudo de farmacovigilância da Alfainterferona 2b Humana Recombinante Produzida Por Bio-Manguinhos - Fiocruz, Utiliz [NCT01841775] | Phase 4 | 85 participants (Actual) | Interventional | 2009-05-31 | Completed |
| BETAEVAL_Global- The New BETACONNECT® Auto-injector: Adherence and EVALuation of MS Patients Treated With Betaferon® [NCT02247310] | | 498 participants (Actual) | Observational | 2014-10-20 | Completed |
| A Phase 3, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of TMC435 Plus Pegylated Interferon Alfa-2a and Ribavirin Administered for 12 Weeks in Treatment-Naïve Subjects With Chronic Genotype 1 or Genotype 4 HCV Infection [NCT01846832] | Phase 3 | 232 participants (Actual) | Interventional | 2013-09-30 | Completed |
| Randomized Phase 2 Study: Neoadjuvant Conditioning of Prostate Cancer Tumor Microenvironment Using a Novel Chemokine-Modulating Regimen [NCT03899987] | Phase 2 | 30 participants (Anticipated) | Interventional | 2019-11-29 | Suspended(stopped due to IFNa2b Supply Shortage) |
| A Phase IV, Open-label, Multicentre, International Trial of Response Guided Treatment With Directly Observed Pegylated Interferon Alfa 2b (PEG-IFN-alfa 2b) and Self Administered Ribavirin (RBV) for Patients With Chronic HCV Genotype 2 or 3 and Injection D [NCT01364090] | Phase 4 | 93 participants (Actual) | Interventional | 2012-06-30 | Completed |
| The Fleming [FMTVDM] Directed CoVid-19 Treatment Protocol [NCT04349410] | Phase 2/Phase 3 | 1,800 participants (Actual) | Interventional | 2020-04-11 | Completed |
| A Randomized, Open-Label, Multicenter Study Investigating AB-729, Nucleos(t)Ide Analogue and Pegylated Interferon Alfa-2a Treatment in Subjects With Chronic Hepatitis B Infection [NCT04980482] | Phase 2 | 43 participants (Actual) | Interventional | 2021-10-29 | Active, not recruiting |
| A Phase IIIb, Randomized, Open-Label Study of Pegylated Interferon Alfa-2A in Combination With Lamivudine or Entecavir Compared With Untreated Control Patients in Children With HBeAg Positive Chronic Hepatitis B in the Immune-Tolerant Phase [NCT02263079] | Phase 3 | 62 participants (Actual) | Interventional | 2014-06-16 | Completed |
| An Open-label Randomized Controlled Trial on Interferon β-1b and Hydroxychloroquine Combination Versus Hydroxychloroquine Alone, as Treatment for COVID-19 Infection [NCT04350281] | Phase 2 | 60 participants (Actual) | Interventional | 2020-04-09 | Completed |
| International Multicenter Randomized Double-blind Crossover Study of Pharmacokinetics, Pharmacodynamics and Tolerability of BCD-033 (CJSC BIOCAD, Russia) and Rebif® (Merck Serono S.p.А., Italy) After Single Subcutaneous Administration to Healthy Volunteer [NCT01766024] | Phase 1 | 32 participants (Actual) | Interventional | 2013-02-28 | Completed |
| A Phase II Multicenter, Parallel-Group, Randomized, Dose-Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Following 12 Weeks of Oral Administration of GSK2336805 With Pegylated Interferon and Ribavirin in Treat [NCT01648140] | Phase 2 | 286 participants (Actual) | Interventional | 2012-08-01 | Completed |
| Combined Virological and Immunological Evaluation of Treatment of Patients With Early HTLV-1-Associated Myelopathy With Recombinant Human Interferon Beta-1a [NCT00001785] | Phase 2 | 12 participants | Interventional | 1998-09-30 | Completed |
| A Phase I Pilot Study of the Safety and Efficacy of Interferon Alfa-2b (IFN Alfa-2b) in Combination With Nucleoside Analog Therapy in Patients With Combined Hepatitis C (HCV) and Advanced Human Immunodeficiency Virus (HIV) Infections [NCT00001035] | Phase 1 | 10 participants | Interventional | | Completed |
| A Phase 3, Multi-Center, Randomized, Double-Blind, Double-Dummy, Active Controlled, Parallel Group Study To Evaluate The Efficacy And Safety Of RPC1063 Administered Orally To Relapsing Multiple Sclerosis Patients [NCT02294058] | Phase 3 | 1,346 participants (Actual) | Interventional | 2014-12-03 | Completed |
| A Phase IV Study of Recombinant Human Gamma Interferon in Patients With Chronic Granulomatous Diseases of Childhood [NCT00001317] | Phase 4 | 100 participants | Interventional | 1992-05-31 | Completed |
| Treatment of Multiply Drug Resistant Tuberculosis With Interferon Gamma: A Phase I/II Dose Escalation Trial [NCT00001407] | Phase 2 | 30 participants | Interventional | 1994-05-31 | Completed |
| Open-Label, Bridging Study to Determine Efficacy and Safety of Telaprevir, Pegylated-Interferon-alfa-2a and Ribavirin in Treatment- Naïve and Treatment-Experienced Russian Subjects With Genotype 1 Chronic Hepatitis C [NCT01498068] | Phase 3 | 36 participants (Actual) | Interventional | 2012-01-31 | Completed |
| Activation of Alveolar Macrophages by Aerosolized r-metHuIFN-Gamma (IFN-Gamma) in Patients With AIDS [NCT00002433] | | 12 participants | Interventional | | Completed |
| A Trial of Active Intralymphatic Immunotherapy With Interferon-Treated Cells and Cyclophosphamide [NCT00002475] | Phase 2 | 40 participants (Anticipated) | Interventional | 1991-04-30 | Completed |
| RANDOMIZED PHASE II TRIAL OF AUTOLOGOUS TUMOR CELL VACCINE [NCT00002505] | Phase 2 | 0 participants | Interventional | 1992-08-31 | Completed |
| ALPHA INTERFERON, TUMOR INFILTRATING LYMPHOCYTES, AND INTERLEUKIN-2 IN THE TREATMENT OF CANCER [NCT00002733] | Phase 2 | 30 participants (Anticipated) | Interventional | 1996-01-31 | Completed |
| Cohort Study on Efficacy and Safety of Interferon Intermittent Treatment of Chronic Hepatitis B [NCT04028856] | | 400 participants (Actual) | Observational | 2018-06-01 | Completed |
| Prospective Study of Betaferon in Adherence, Coping and Nurse Support in Patients of Chinese Origin With Multiple Sclerosis [NCT01436838] | | 110 participants (Actual) | Observational | 2012-03-31 | Completed |
| An Integrated Phase II/III, Open Label, Randomized and Controlled Study of the Safety and Efficacy of CG0070 Adenovirus Vector Expressing GM-CSF in Patients With NMIBC With Carcinoma In Situ Disease Who Have Failed BCG [NCT01438112] | Phase 2/Phase 3 | 22 participants (Actual) | Interventional | 2014-03-31 | Terminated(stopped due to Change in study design) |
| Directly Observed Hepatitis C Treatment in Methadone Clinics [NCT01442311] | | 80 participants (Actual) | Interventional | 2007-10-31 | Completed |
| A Double-Blinded Randomized Control Study Evaluating the Efficacy and Safety of Pegylated Lambda Interferon Compared to Pegylated Alfa-2a Interferon, Each in Combination With Ribavirin, in the Treatment of Naive Genotype 1 or 4 Chronic Hepatitis C Subject [NCT01447394] | Phase 3 | 0 participants (Actual) | Interventional | 2012-03-31 | Withdrawn |
| Assessing the Effectiveness and Safety of Interferon Bladder Infusion for the Treatment of Interstitial Cystitis: a Randomized, Double-blind, Placebo-controlled Study [NCT05912946] | Phase 2/Phase 3 | 129 participants (Anticipated) | Interventional | 2023-10-15 | Not yet recruiting |
| Pilot Study on the Efficacy of Pegylated Interferon-Ribavirin-Boceprevir Triple Therapy in Patients Infected With Genotype 1 HCV With Cirrhosis and Awaiting Liver Transplantation (ANRS HC 29 BOCEPRETRANSPLANT) [NCT01463956] | Phase 2 | 58 participants (Actual) | Interventional | 2012-01-06 | Completed |
| The Predictive Values of Rapid Virus Response and Complete Early Virus Response for Sustained Virus Response in Chronic Hepatitis C Treated With Individual Therapeutic Programme [NCT01464008] | | 297 participants (Actual) | Observational | 2004-01-31 | Completed |
| Comparison of Polyethylene Glycol-Interferon Alfa-2B (PEG-Intron, SCH 54031) vs. Interferon Alfa-2B for Treatment of Adult Subjects With Chronic Hepatitis C Not Previously Treated With Interferon: Dose Finding Study [NCT03537274] | Phase 2/Phase 3 | 1,224 participants (Actual) | Interventional | 1997-08-05 | Completed |
| Phase I-II Study of the Combination Vemurafenib Plus Cobimetinib Plus PEG-interferon in Advanced Melanoma Patients Harboring the V600BRAF Mutation [NCT01959633] | Phase 1/Phase 2 | 11 participants (Actual) | Interventional | 2014-04-03 | Completed |
| Parallel, Open-Label, Randomized, Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-790052 and BMS-650032 in Combination in Null Responders to Standard of Care Infected With Chronic Hepatitis C Virus Genotype 1 [NCT01012895] | Phase 2 | 215 participants (Actual) | Interventional | 2009-12-31 | Completed |
| Assessment of the Biochemical Response to Interferon-Gamma in Subjects With Specific Gene Mutation in Chronic Granulomatous Disease [NCT01147042] | Phase 4 | 2 participants (Actual) | Interventional | 2010-05-18 | Terminated(stopped due to Early termination due to only 2 subjects completing trial.) |
| A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Three Preparations of Low-Dose Oral Alpha Interferon in HIV-Infected Patients With CD4+ Counts >= 50 and <= 350 Cells/mm3 [NCT00000844] | | 560 participants | Interventional | | Completed |
| Impact of Interleukin 28B (rs12979860) Genotype on Virological Responses in Chronic Hepatitis C Treatment [NCT03090035] | Phase 3 | 98 participants (Actual) | Interventional | 2014-01-01 | Completed |
| Evaluation of Treatment With Interferon, Octreotide, or Their Combination in Patients With Zollinger-Ellison Syndrome and Progressive Metastatic Non-B Islet Cell Neoplasm [NCT00001228] | Phase 2 | 50 participants | Interventional | 1988-10-25 | Completed |
| Treatment of Non-Tuberculous Mycobacterial Infections With Interferon Gamma [NCT00001318] | Phase 2 | 60 participants | Interventional | 1992-08-31 | Completed |
| A Randomized Trial to Evaluate the Safety and Efficacy of Combination Therapy With Retrovir ( AZT ) and HIVID ( ddC ) Versus Retrovir, HIVID, and Wellferon ( Interferon Alfa-n1 ) for the Treatment of HIV Infection [NCT00002086] | Phase 2 | 256 participants | Interventional | | Completed |
| A Phase I Trial of Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor (rHuGM-CSF), Recombinant Alpha Interferon and Azidothymidine (AZT) in AIDS-Associated Kaposi's Sarcoma [NCT00000694] | Phase 1 | 18 participants | Interventional | | Completed |
| ALPHA INTERFERON AND CIS-RETINOIC ACID FOR THE TREATMENT OF SQUAMOUS CELL CARCINOMAS [NCT00002506] | Phase 2 | 0 participants | Interventional | 1992-08-31 | Completed |
| Standard Dose Versus Myeloablative Therapy for Previously Untreated Symptomatic Multiple Myeloma, A Phase III Intergroup Study [NCT00002548] | Phase 3 | 899 participants (Actual) | Interventional | 1994-01-31 | Completed |
| PHASE I STUDY OF INTERFERON ENHANCED INTRAPERITONEAL RADIOIMMUNO-CHEMOTHERAPY FOR OVARIAN CANCER [NCT00002734] | Phase 1 | 30 participants (Actual) | Interventional | 1996-03-31 | Completed |
| Combination Chemobiotherapy With Gemcitabine, 5-Fluorouracil, Interleukin-2 and Alpha Interferon in Patients With Metastatic or Unresectable Renal Cell Cancer. A Phase II Study [NCT00003664] | Phase 2 | 30 participants (Anticipated) | Interventional | 1998-10-31 | Active, not recruiting |
| Drug Repurposing Using Metformin for Improving the Therapeutic Outcome in Multiple Sclerosis Patients [NCT05298670] | Phase 2 | 80 participants (Anticipated) | Interventional | 2022-02-01 | Recruiting |
| [NCT00004402] | Phase 3 | 30 participants | Interventional | 1999-11-30 | Completed |
| [NCT00004450] | | 60 participants | Interventional | 1998-08-31 | Completed |
| [NCT00004804] | Phase 3 | 57 participants | Interventional | 1993-08-31 | Completed |
| Effect of Interferon Alpha 2b Intensification on HIV-1 Residual Viremia in Individuals Suppressed on Antiretroviral Therapy [NCT01295515] | Phase 1/Phase 2 | 7 participants (Actual) | Interventional | 2011-02-11 | Completed |
| Pilot Study on Innate Activation and Viral Control in HIV-Infected Adults Undergoing an Analytical Treatment Interruption After Administration of Pegylated Interferon Alpha 2b With Broadly HIV-1 Neutralizing Antibodies (3BNC117, 10-1074) [NCT03588715] | Phase 1 | 15 participants (Actual) | Interventional | 2020-06-18 | Active, not recruiting |
| The Observational Study of COVID-19 Infection and Its Clinical Prognosis in Chronic Hepatitis B Patients With Antiviral Therapy [NCT05792878] | | 600 participants (Anticipated) | Observational | 2022-09-01 | Recruiting |
| A Randomized, Multicenter, Two Arm, Open Label, Twelve Week Phase IIIb Study to Evaluate the Tolerability of Rebif (New Formulation) (IFN Beta-1a) and Betaseron (IFN Beta-1b) in IFN-naive Subjects With Relapsing Remitting Multiple Sclerosis (RRMS) Followe [NCT00428584] | Phase 3 | 129 participants (Actual) | Interventional | 2006-12-31 | Completed |
| Efficacy and Safety of Pegylated Proline Interferon Alpha 2b (AOP2014) in Maintaining Deep Molecular Remissions in Patients With Chronic Myeloid Leukemia (CML) Who Discontinue ABL-Kinase Inhibitor Therapy - a Randomized Phase III, Multicenter Trial With P [NCT03117816] | Phase 3 | 214 participants (Actual) | Interventional | 2017-05-04 | Completed |
| An Open-label Multicenter Study to Assess Response to COVID-19 Vaccine in Participants With Multiple Sclerosis Treated With Ofatumumab 20 mg Subcutaneously [NCT04878211] | Phase 4 | 24 participants (Actual) | Interventional | 2021-06-10 | Terminated(stopped due to Terminated by sponsor) |
| Plegridy™ (Peginterferon β-1a) Real World Effectiveness and Safety Observational Program [NCT02230969] | | 1,208 participants (Actual) | Observational | 2014-11-12 | Completed |
| Evaluating the Efficacy and Safety of Bromhexine Hydrochloride Tablets Combined With Standard Treatment/ Standard Treatment in Patients With Suspected and Mild Novel Coronavirus Pneumonia (COVID-19) [NCT04273763] | | 18 participants (Actual) | Interventional | 2020-02-16 | Active, not recruiting |
| A Phase I Study of PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma. [NCT01462773] | Phase 1 | 16 participants (Actual) | Interventional | 2006-01-31 | Completed |
| A Phase II Trial of Pancreaticoduodenectomy Plus Postoperative Cisplatin, Interferon Alfa-2b, and 5-FU Combined With Radiation Treatment for Patients With Resected Pancreatic Adenocarcinoma [NCT00068575] | Phase 2 | 29 participants (Actual) | Interventional | 2002-05-31 | Completed |
| A Single Center, Prospective Phase IV, Open-Label, Randomized Trial Comparing the Efficacy , Tolerability, and Safety of Quadritherapy Regimen (Reiferon Retard® + Ribavirin + Nitazoxanide + Alfacalcidol ( Bon-One ®) ) Versus Triple Therapy Regimen (Reifer [NCT01896609] | Phase 4 | 300 participants (Anticipated) | Interventional | 2013-06-30 | Recruiting |
| UARK 98-026, Total Therapy II - A Phase III Study for Newly Diagnosed Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy [NCT00083551] | Phase 3 | 668 participants (Actual) | Interventional | 1998-08-31 | Completed |
| A Phase II Study of Pegylated Interferon Alfa-2b (Peg-Intron (TM)) in Children With Diffuse Pontine Gliomas [NCT00036569] | Phase 2 | 32 participants (Actual) | Interventional | 2002-05-31 | Completed |
| RESOunD: REbif Satisfaction On Discontinuing Oral Dimethyl Fumarate. A 24-week, Prospective, Open-label, Multicenter Trial Evaluating Treatment Satisfaction in Subjects With Relapsing Forms of Multiple Sclerosis Following Treatment Change From Tecfidera™ [NCT02117050] | Phase 4 | 1 participants (Actual) | Interventional | 2014-06-30 | Terminated(stopped due to recruitment challenges) |
| A Phase I/II Dose-Finding Study to Determine the Safety, Tolerability, and Anti-Leukemic Effects of STI571 (NSC 716051) in Combination With Interferon-alpha in Patients With Chronic Myelogenous Leukemia in Chronic Phase [NCT00015847] | Phase 2 | 25 participants (Actual) | Interventional | 2001-04-30 | Terminated |
| A Phase 2 Study of Bevacizumab and Interferon-Alpha-2b in Metastatic Malignant Melanoma [NCT00026221] | Phase 2 | 57 participants (Actual) | Interventional | 2001-11-30 | Completed |
| Safety and Activity of Rituximab(HLX01) in Combination With Pegylated Interferon α-2b in Patients With Newly Diagnosed Advanced Indolent B-cell Lymphoma: a Single-arm, Multicenter, Phase 2 Study [NCT04246359] | Phase 2 | 52 participants (Anticipated) | Interventional | 2020-01-15 | Recruiting |
| The Role Of Nitazoxanide, Interferon Alfa And Ribavirin In Treatment Of Hepatitis C Infected Type 2 Diabetic Patients [NCT01770483] | Phase 4 | 66 participants (Actual) | Interventional | 2011-07-31 | Completed |
| Open Label Phase I Study of Single Agent Oral RG7388 in Patients With Polycythemia Vera and Essential Thrombocythemia (With Pilot Feasibility Study in Combination With Pegylated Interferon Alfa 2a for Patients Who do Not Respond to the Single Agent at Eac [NCT02407080] | Phase 1 | 13 participants (Actual) | Interventional | 2015-04-30 | Completed |
| Pilot Study of Mesenchymal Stromal Cells in Patients With Xerostomia After Radiation Therapy for Head and Neck Cancer [NCT04489732] | Phase 1 | 6 participants (Actual) | Interventional | 2022-02-18 | Active, not recruiting |
| A Phase I/II Randomized, Double-blind, Placebo-controlled Study of Inhaled Interferon α2b for the Treatment of Coronavirus Disease 19 (COVID-19) [NCT04988217] | Phase 1/Phase 2 | 173 participants (Actual) | Interventional | 2021-09-15 | Completed |
| A Multicenter, Open-Label Study to Evaluate ARC-520 Administered Alone and in Combination With Other Therapeutics in Patients With Chronic Hepatitis B Virus (HBV) Infection (MONARCH) [NCT02577029] | Phase 2 | 79 participants (Actual) | Interventional | 2015-12-31 | Terminated(stopped due to Company decision to discontinue trial) |
| Feasibility of Assessing Drug Response to Precise Local Injection of Anti-cancer Drugs Using Presage's CIVO Device in Soft Tissue Sarcoma Patients Undergoing Surgery. [NCT03056599] | Phase 1 | 23 participants (Actual) | Interventional | 2016-12-15 | Completed |
| Evaluate the Efficacy and Safety of TG-2349 in Combination With Peg-interferon and Ribavirin in Treatment naïve East Asian Subjects With Chronic Hepatitis C Virus Genotype 1b Infection. [NCT02340962] | Phase 2 | 25 participants (Actual) | Interventional | 2015-05-31 | Completed |
| Open-Label, Phase 3b Study To Determine Efficacy and Safety of Telaprevir, Pegylated-Interferon-alfa-2a and Ribavirin in Hepatitis C Genotype 1 Infected, Stable Liver Transplant Subjects [NCT01571583] | Phase 3 | 74 participants (Actual) | Interventional | 2012-02-29 | Completed |
| An Open-Label Safety and Tolerability Study of Nitazoxanide, Pegylated-Interferon Alfa 2a and Ribavirin in HIV/HCV Co-Infected Genotype 1 Prior Treatment Relapsers and Non-Responders [NCT01185028] | Phase 1/Phase 2 | 8 participants (Actual) | Interventional | 2010-08-31 | Completed |
| COMparison Between All immunoTherapies for Multiple Sclerosis. An Observational Long-term Prospective Cohort Study of Safety, Efficacy and Patient's Satisfaction of MS Disease Modulatory Treatments in Relapsing-remitting Multiple Sclerosis [NCT03193866] | | 3,526 participants (Actual) | Observational [Patient Registry] | 2017-06-02 | Active, not recruiting |
| Granulocyte-Macrophage Colony Stimulating Factor (Rhu-GM-CSF) With Interferon-Alpha (IFN-alpha) for Chronic Myeloid Leukemia [NCT00003561] | Phase 2 | 48 participants (Anticipated) | Interventional | 1998-02-28 | Terminated |
| Prospective Randomized Pilot Study of Daily Consensus Interferon (CIFN) and Ribavirin for 52 Wks vs Extended Duration 72 Wks Based on Virologic Response for the Initial Treatment of Difficult-to-treat Patients With Chronic HCV Genotype 1 [NCT00211692] | Phase 3 | 64 participants (Actual) | Interventional | 2005-07-31 | Completed |
| A Phase I/II Study of Nivolumab Plus 5-Fluorouracil Plus Interferon-α2b for Unresectable Fibrolamellar Hepatocellular Carcinoma [NCT04380545] | Phase 1/Phase 2 | 15 participants (Anticipated) | Interventional | 2021-01-13 | Recruiting |
| A Pilot Study to Characterize Interferon-Induced Gene Expression in Liver Cells and Peripheral Blood Lymphocytes Using High Density Oligonucleotide Microarray Expression Analysis in Caucasian and African American Patients With Chronic Hepatitis C [NCT00324389] | Phase 2 | 2 participants | Interventional | 2006-05-31 | Completed |
| The Treatment of Macular Edema Secondary to Uveitis Using Topical Interferon Gamma [NCT01376362] | Phase 1/Phase 2 | 5 participants (Actual) | Interventional | 2011-06-30 | Completed |
| Double-Blind, Randomized, Dose Ranging Study of Alferon LDO (Low Dose Oral Interferon Alfa-n3 (Human Leukocyte Derived)) in HIV+ Subjects [NCT00002018] | | 60 participants | Interventional | | Completed |
| A Phase I Study To Determine the Safety of the Optimal Monocyte Activating Administration Schedule of Subcutaneous Human Recombinant Interferon-gamma in ZDV-Treated Patients With AIDS [NCT00001112] | Phase 1 | 5 participants | Interventional | | Completed |
| Phase I Study of Alferon N Injection in Persons With Asymptomatic Human Immunodeficiency Virus (HIV) Infection [NCT00002078] | Phase 1 | 0 participants | Interventional | | Completed |
| Open-label Pilot Study of Interferon Gamma-1b (Actimmune™) for the Treatment of Friedreich Ataxia (FRDA) [NCT01965327] | Phase 2 | 12 participants (Actual) | Interventional | 2013-08-31 | Completed |
| Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy, Safety, and Pharmacokinetic Study of ACTIMMUNE® (Interferon γ-1b) in Children and Young Adults With Friedreich's Ataxia [NCT02415127] | Phase 3 | 92 participants (Actual) | Interventional | 2015-06-30 | Completed |
| Safety and Tolerance of Zidovudine and Interferon-Alpha in HIV-Infected Children [NCT00000967] | Phase 1 | 52 participants | Interventional | | Completed |
| Randomized Study on the Efficacy and Safety of Pegylated Interferon and Ribavirin in Hepatitis C Virus Infection After Liver Transplantation [NCT00383864] | Phase 4 | 55 participants | Interventional | 2001-07-31 | Completed |
| A Study of Peg-interferon Treatment for Nucleos(t)Ide Analogues Suppressed Chronic Hepatitis B Patients With Low Level Hepatitis Surface Antigen [NCT04035837] | Phase 4 | 30,000 participants (Anticipated) | Interventional | 2018-05-16 | Recruiting |
| S9805, Phase II Study of Tandem High Dose Melphalan Supported by Peripheral Blood Stem Cell Support in Waldenstrom's Macroglobulinemia (WM) [NCT00003416] | Phase 2 | 9 participants (Actual) | Interventional | 1998-09-30 | Completed |
| Adjuvant Therapy for Melanoma Patients With Regional Lymph Node Metastases With Interferon Alfa-2B vs. Biochemotherapy Using Cisplatin + Vinblastine + DTIC + Interferon Plus IL-2 [NCT00002882] | Phase 3 | 140 participants (Actual) | Interventional | 1995-11-30 | Completed |
| MYELOMA VII MEDICAL RESEARCH COUNCIL WORKING PARTY ON LEUKEMIA IN ADULTS: MYELOMATOSIS THERAPY TRIAL [NCT00002599] | Phase 3 | 750 participants (Anticipated) | Interventional | 1994-09-30 | Active, not recruiting |
| Phase I Trial of Immunotherapy With Adenovirus-Interferon- Gamma (TG1041) in Patients With Malignant Melanoma [NCT00004016] | Phase 1 | 0 participants | Interventional | 1999-04-30 | Completed |
| Patients With Chronic Lymphocytic Leukemia or Multiple Myeloma Whose Disease Has Been Controlled With Chemotherapy: Rituximab Anti-CD20 Monoclonal Antibody or Interferon Alpha 2-b as Maintenance Therapy [NCT00004040] | Phase 2 | 0 participants (Actual) | Interventional | 1998-06-30 | Withdrawn(stopped due to no patient accruals) |
| A RANDOMIZED PHASE II TRIAL OF INTERFERON ALPHA-2A WITH AND WITHOUT 13-CIS RETINOIC ACID IN PATIENTS WITH PROGRESSIVE MEASURABLE METASTATIC RENAL CELL CARCINOMA. Amendment Protocol: Extension to a Randomized Phase III Trial [NCT00002737] | Phase 3 | 320 participants (Actual) | Interventional | 1996-03-31 | Completed |
| PHASE III TRIAL OF MELACINE PLUS INTERFERON ALFA-2B VERSUS INTERFERON ALFA-2B IN PATIENTS WITH DISSEMINATED MALIGNANT MELANOMA [NCT00002767] | Phase 3 | 300 participants (Anticipated) | Interventional | 1996-01-31 | Active, not recruiting |
| A CLINICAL TRIAL FOR PANCREAS CANCER USING ACTIVE INTRALYMPHATIC IMMUNOTHERAPY WITH INTERFERON-TREATED PANCREAS CANCER TISSUE CULTURE CELLS, GMCSF, AND LOW-DOSE CYCLOPHOSPHAMIDE [NCT00002773] | Phase 2 | 0 participants | Interventional | 1996-05-31 | Completed |
| Phase I Trial of rhIL-12 and rHuIFN-a2b in Patients With Metastatic Renal Cell Carcinoma or Malignant Melanoma [NCT00004244] | Phase 1 | 30 participants (Actual) | Interventional | 2000-03-31 | Completed |
| Open-Label, Randomized, Multicenter, Multiple-Dose,Active-Controlled, Parallel-Group, Efficacy and Safety Study of BG00012 in Children From 10 to Less Than 18 Years of Age With Relapsing-Remitting Multiple Sclerosis, With Optional Open-Label Extension [NCT02283853] | Phase 3 | 156 participants (Actual) | Interventional | 2014-08-28 | Active, not recruiting |
| Interferon Maintenance in Advanced Multiple Myeloma After Using High-Dose Melphalan as Myeloablative Chemotherapy: A Pilot Study [NCT00003007] | Phase 2 | 0 participants | Interventional | 1996-07-31 | Completed |
| Phase I Trial of Interleukin-12 Followed by Interferon-Alpha [NCT00003451] | Phase 1 | 40 participants (Actual) | Interventional | 1998-08-31 | Completed |
| PROSPECTIVE RANDOMISED STUDY TO COMPARE LOW-DOSE INTERFERON-ALPHA-n1 (WELLFERON) +/- HYDROXYUREA VS HIGH-DOSE INTERFERON-ALPHA-n1 (WELLFERON) +/- HYDROXYUREA IN PATIENTS WITH NEWLY DIAGONISED CHRONIC PHASE CHRONIC MYELOID LEUKAEMIA [NCT00002869] | Phase 3 | 800 participants (Anticipated) | Interventional | 1995-04-30 | Active, not recruiting |
| Treatment of Metastatic Renal Cell Carcinoma and Melanoma With Subsequential High-Dose Subcutaneous Interferon Alfa-2b and High-Dose Bolus and Continuous Intravenous Interleukin-2 [NCT00003091] | Phase 2 | 40 participants (Anticipated) | Interventional | 1996-01-31 | Completed |
| A Prospective, Randomized, Open-Label, Comparative Clinical Trial in Post-Surgical Melanoma Patients With Either DNP-Modified Autologous Tumor Vaccine or Interferon Alpha-2b [NCT00003715] | Phase 2 | 425 participants (Anticipated) | Interventional | 1998-12-31 | Terminated(stopped due to Terminated: recruiting or enrolling participants has halted prematurely and will not resume; participants are no longer being examined or treated) |
| Non-interventional Study to Observe Triple Combination Therapy With Boceprevir or Simeprevir Plus Peginterferon Alfa-2a Plus Ribavirin for Re-treatment of Chronic Hepatitis C in Hungary (IMPERIAL) [NCT02118597] | | 19 participants (Actual) | Observational | 2014-05-31 | Terminated(stopped due to Study terminated due to the Sponsor's decision.) |
| [NCT00005665] | Phase 2 | 0 participants | Interventional | | Active, not recruiting |
| Noninterventional Study on the Quality Assurance of the Therapy of Chronic Hepatitis C With Peg-(40kd)-Interferon Alfa-2a (Pegasys®) and Ribavirin (e.g. Copegus®) With Main Focus Gastroenterologists - a Project in BNG (Association of German Resident Gastr [NCT02106156] | | 10,228 participants (Actual) | Observational | 2008-01-31 | Completed |
| A Phase 2/3, Multi-center, Randomized, Double-blind, Placebo-controlled (Part A) and Double-blind, Double-dummy, Active-controlled (Part B), Parallel Group Study to Evaluate the Efficacy and Safety of RPC1063 Administered Orally to Relapsing Multiple Scle [NCT02047734] | Phase 3 | 1,320 participants (Actual) | Interventional | 2013-12-03 | Completed |
| An Open-Label, Two-Arm Randomized Study to Characterize Flu-Like Symptoms in Relapsing Multiple Sclerosis Patients Transitioning From Current Interferon Beta Therapies to BIIB017 [NCT01939002] | Phase 3 | 251 participants (Actual) | Interventional | 2013-11-30 | Completed |
| Multicenter, Open Label, Randomized and Parallel Group Phase IV Pilot Study Evaluating the Effectiveness of Functional Rehabilitation Protocol in RRMS Patients Treated With Betaferon® [NCT00780455] | Phase 4 | 4 participants (Actual) | Interventional | 2008-10-31 | Terminated |
| Open Label Phase I Study To Evaluate the Safety of Combination Therapy With AZT and Interferon-Beta in Patients With AIDS Related Kaposi's Sarcoma [NCT00000695] | Phase 1 | 36 participants | Interventional | | Completed |
| [NCT02359877] | Phase 1 | 60 participants (Actual) | Interventional | 2014-07-31 | Completed |
| TREATMENT OF METASTATIC MELANOMA WITH DTIC, CDDP AND IFN ALPHA WITH OR WITHOUT IL-2: A RANDOMIZED PHASE III TRIAL [NCT00002669] | Phase 2 | 90 participants (Anticipated) | Interventional | 1995-06-30 | Completed |
| A Comparative Study of High-dose Interferon Alfa-2a and Pegylated Interferon Alfa-2a for Induction Therapy in Difficult to Treat Genotype 1 Patients With Chronic HCV [NCT00381953] | Phase 3 | 33 participants (Actual) | Interventional | 2003-02-28 | Completed |
| Adjuvant Chemoimmunotherapy for Colorectal Cancer [NCT00003063] | Phase 3 | 1,050 participants (Anticipated) | Interventional | 1991-11-30 | Active, not recruiting |
| A Phase 3 Study Evaluating the Safety and Efficacy of Lambda/Ribavirin/Daclatasvir in Subjects With Chronic HCV Infection and Underlying Hemophilia Who Are Treatment Naïve or Are Prior Relapsers to Peginterferon Alfa-2a/Ribavirin [NCT01741545] | Phase 3 | 71 participants (Actual) | Interventional | 2013-03-31 | Completed |
| Prospective Phase IV Clinical Trial on Effectiveness of Rebif Treatment of CIS and RMS Patients in Romania Using Electronic Device RebiSmart™ [NCT02254304] | Phase 4 | 106 participants (Actual) | Interventional | 2014-12-31 | Completed |
| Danish Study of Low-dose Interferon Alpha Versus Hydroxyurea in the Treatment of Philadelphia Chromosome Negative (Ph-)Chronic Myeloid Neoplasms. [NCT01387763] | Phase 3 | 202 participants (Actual) | Interventional | 2012-01-31 | Completed |
| A Phase I/IIa Study of SV-BR-1-GM in Metastatic or Locally Recurrent Breast Cancer Patients [NCT03066947] | Phase 1/Phase 2 | 24 participants (Actual) | Interventional | 2017-05-05 | Completed |
| Boceprevir/Peginterferon Alfa (PegIFN α)-2b/Ribavirin (Riba) in Difficult-to-Treat Menopausal Women With Chronic Hepatitis C Genotype 1 (Gt 1), Either Deemed Nonresponders to Peginterferon/Ribavirin or Treatment-naives (MEN_BOC) [NCT01457937] | Phase 3 | 240 participants (Anticipated) | Interventional | 2011-11-30 | Recruiting |
| A Phase II Study of Total Marrow Irradiation, Busulfan, and Alpha-Interferon Followed by Allogeneic Peripheral Blood Stem Cell or Marrow Transplantation for Treatment of Patients With Advanced Multiple Myeloma. [NCT00003195] | Phase 2 | 0 participants | Interventional | 1997-12-31 | Completed |
| Treatment Protocol for Patients With Standard Risk Acute Myelogenous Leukemia and Its Variants: Induction Using High-Dose Cytarabine, Mitoxantrone and Ethyol; Consolidation With Cytarabine and Idarubicin and Maintenance With 13 Cis Retinoic Acid and Alpha [NCT00003405] | Phase 2 | 0 participants (Actual) | Interventional | 1998-04-30 | Withdrawn(stopped due to No enrollment) |
| A Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-2218 Alone or in Combination With Pegylated Interferon Alpha-2a [NCT04412863] | Phase 2 | 84 participants (Actual) | Interventional | 2020-07-03 | Active, not recruiting |
| An Investigation Into Beneficial Effects of Interferon Beta 1a, Compared to Interferon Beta 1b And The Base Therapeutic Regiment in Moderate to Severe COVID-19: A Randomized Clinical Trial [NCT04343768] | Phase 2 | 60 participants (Actual) | Interventional | 2020-04-09 | Completed |
| A Multicenter, Prospective Cohort Study: Efficacy of NA Combined With PEG-IFN-α2b Continuous Versus Pulsed Therapy for 96 Weeks in Patients With Chronic Hepatitis B. [NCT05922306] | Early Phase 1 | 1,084 participants (Anticipated) | Interventional | 2023-07-31 | Recruiting |
| Phase II Study of Low Dose Peginterferon Alfa-2b in Patients With Metastatic Melanoma Over-Expressing Basic Fibroblast Growth Factor [NCT00049530] | Phase 2 | 32 participants (Actual) | Interventional | 2004-01-13 | Completed |
| Autologous and Allogeneic Bone Marrow Transplantation for Low Grade Lymphoma [NCT00002829] | Phase 2 | 45 participants (Actual) | Interventional | 1994-02-28 | Completed |
| A Randomized Prospective Study of Early Intensification Versus Alternating Triple Therapy for Patients With Poor Prognosis Lymphoma [NCT00002835] | Phase 3 | 116 participants (Actual) | Interventional | 1995-10-30 | Completed |
| TREATMENT OF METASTATIC RENAL CELL CARCINOMA WITH SUBCUTANEOUS RECOMBINANT INTERLEUKIN-2 AND INTERFERON ALPHA [NCT00002847] | Phase 2 | 14 participants (Anticipated) | Interventional | 1995-09-30 | Active, not recruiting |
| A Phase I/II Pilot Study of a Novel Four Drug Regimen for the Treatment of Advanced Renal Cell Carcinoma: FUNIL-cRA [NCT00003585] | Phase 1/Phase 2 | 35 participants (Anticipated) | Interventional | 1996-08-31 | Completed |
| Pilot Study of Intensive Chemotherapy Followed by Peripheral Blood Stem Cell Harvesting for Autotransplantation of Adults With Chronic Myelogenous Leukemia and High Risk Acute Leukemia [NCT00004905] | Phase 2 | 0 participants | Interventional | 1999-10-31 | Completed |
| Randomised Controlled Trial of CID (Chlorambucil, Idarubicin, Dexamethasone) Versus CD (Chlorambucil, Dexamethasone) for Induction of Remission in Low Grade Non-Hodgkin's Lymphoma (Kiel Classification) Followed by Randomised Controlled Assessment of Stand [NCT00003639] | Phase 3 | 200 participants (Anticipated) | Interventional | 1993-11-30 | Active, not recruiting |
| Directly Observed Therapy for the Delivery of HCV Therapy Among HCV-infected Individuals in Chennai, India [NCT02541409] | Phase 2 | 50 participants (Actual) | Interventional | 2015-09-30 | Completed |
| Phase 4 Study of Peg-interferon Plus Ribavirin Therapy for Prevention of Hepatocellular Carcinoma [NCT00375661] | Phase 4 | 100 participants (Actual) | Interventional | 2006-09-30 | Completed |
| An Open-Label, Randomized, Multicenter, Active-Controlled, Parallel-Group Study to Evaluate the Safety, Tolerability, and Efficacy of BIIB017 in Pediatric Subjects Aged 10 to Less Than 18 Years for the Treatment of Relapsing-Remitting Multiple Sclerosis, [NCT03958877] | Phase 3 | 142 participants (Anticipated) | Interventional | 2019-10-18 | Recruiting |
| A Phase 1 Dose Escalation Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Percutaneously-Accessible Solid Tumors and Mycosis Fungoides [NCT02890368] | Phase 1 | 56 participants (Actual) | Interventional | 2016-09-30 | Terminated |
| Combination Therapy of Interferon Alfa-2b Plus Interleukin 2 and Hepatitis B Vaccine in Entecavir-experienced Chronic Hepatitis B Patients With HBeAg Seroclearance: a Prospective, Randomized Open-label Trial (Endeavor Study, a Pilot Study) [NCT02360592] | Phase 4 | 94 participants (Actual) | Interventional | 2013-06-30 | Completed |
| A Prospective, Phase III, Open-Label Study of Boceprevir, Pegylated-Interferon Alfa 2b and Ribavirin in HCV/HIV Coinfected Subjects [NCT01482767] | Phase 3 | 262 participants (Actual) | Interventional | 2012-04-30 | Completed |
| A Randomized Phase 2 Trial of Peginterferon Lambda-1a (Lambda) for the Treatment of Hospitalized Patients Infected With SARS-CoV-2 With Non-critical Illness [NCT04388709] | Phase 2 | 0 participants (Actual) | Interventional | 2020-09-30 | Withdrawn(stopped due to Due to the number of competing trials at their site, the study team has closed enrollment and withdrawn this trial.) |
| A Phase 3b Study of 2 Treatment Durations of Telaprevir, Peg-IFN (Pegasys®), and Ribavirin (Copegus®) in Treatment-Naive and Prior Relapser Subjects With Genotype 1 Chronic Hepatitis C and IL28B CC Genotype [NCT01459913] | Phase 3 | 239 participants (Actual) | Interventional | 2011-11-30 | Terminated(stopped due to The study was terminated early by the sponsor on 13 January 2014 due to a decision to modify the drug development plan.) |
| A 2-Part, Open Label Study of Telaprevir in Combination With Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Subjects Chronically Infected With Genotype 1 Hepatitis C Virus Following Liver Transplantation [NCT01467505] | Phase 2 | 61 participants (Actual) | Interventional | 2012-02-29 | Terminated(stopped due to The study was terminated early by the sponsor on 13 January 2014 due to a decision to modify the drug development plan.) |
| A Personalized Randomized Trial of Validation and Restoration of Immune Dysfunction in Severe Infections and Sepsis [NCT03332225] | Phase 2 | 36 participants (Actual) | Interventional | 2017-12-15 | Completed |
| A Phase II Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of 4 Different Regimens of MK-7009 When Administered Concomitantly With Pegylated Interferon and Ribavirin in Treatment-Experienced Patients With Chronic Ge [NCT00704405] | Phase 2 | 285 participants (Actual) | Interventional | 2009-03-27 | Completed |
| A Phase II Randomized, Double-blind, Placebo-controlled, Multi-center, Dose-effect Relationship Study of Hepalatide for Injection Combined With Pegylated Interferon in Subjects With Chronic Hepatitis B [NCT04426968] | Phase 2 | 96 participants (Actual) | Interventional | 2021-06-18 | Completed |
| A Phase 3, Matrix Design, Partially Double-Blind, Randomized Study of the Efficacy and Safety of 50 mg Lonafarnib/100 mg Ritonavir BID With and Without 180 mcg PEG IFN-alfa-2a for 48 Weeks Compared With PEG IFN-alfa-2a Monotherapy and Placebo Treatment in [NCT03719313] | Phase 3 | 407 participants (Actual) | Interventional | 2018-12-01 | Completed |
| A Pilot Study of the Efficacy of Recombinant Alpha Interferon (IFN-A2b) and Zidovudine (AZT) in the Treatment of Progressive Multifocal Leukoencephalopathy (PML) Complicating HIV-1 Infection [NCT00002270] | | 0 participants | Interventional | | Completed |
| Randomized Prospective Comparative Study of Interferon α2a and Cyclosporine in Patients With Refractory Behçet's Disease Uveitis [NCT03209219] | Phase 3 | 28 participants (Actual) | Interventional | 2017-06-30 | Completed |
| A Phase 2a Open-label Study of the Oral Farnesoid X Receptor (FXR) Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B (CHB) Patients in Combination With Pegylated Interferon alpha2a (Peg-IFN) Alone and With Entecavir (ETV) [NCT04365933] | Phase 2 | 20 participants (Actual) | Interventional | 2020-05-25 | Completed |
| Multicenter, Safety and Efficacy, Open-Label Extension Study of ACTIMMUNE® (Interferon γ-1b) in Children and Young Adults With Friedreich's Ataxia [NCT02593773] | Phase 3 | 86 participants (Actual) | Interventional | 2015-12-25 | Completed |
| Phase I/II Study of Subcutaneous Administration of Pegylated-Interferon Alpha-2A (RO 25-8310) in Previously Untreated Patients With Locally Advanced or Metastatic Renal Cell Carcinoma [NCT00003542] | Phase 1/Phase 2 | 58 participants (Anticipated) | Interventional | 1998-05-31 | Completed |
| Open-label, Randomized, 2-arm, Active Comparator Study to Evaluate Safety and Tolerability in Portuguese Patients With Relapsing Remitting Multiple Sclerosis (MS) Transitioning From Current Subcutaneous Interferon Therapy to Peginterferon Beta 1a (PLEGRID [NCT03177083] | Phase 4 | 80 participants (Actual) | Interventional | 2017-01-30 | Completed |
| A Phase II Randomized, Control, Multi-center Study of Recombinant Humanized Anti-PD-1 mAb for Injection Compared to High-Dose Interferon In Patients With Mucosal Melanoma That Has Been Removed by Surgery [NCT03178123] | Phase 2 | 220 participants (Anticipated) | Interventional | 2017-05-31 | Active, not recruiting |
| Autotransplantation for Chronic Myelogenous Leukemia (CML) Followed by Immunotherapy With Ex-Vivo Expanded Autologous T Cells [NCT00003727] | Phase 2 | 22 participants (Anticipated) | Interventional | 1999-03-31 | Completed |
| A Phase I-II Clinical Trial of Cisplatin (Platinol) Followed by Gemcitabine HCl (Gemzar) in Combination With Mild, Fever-Range Whole Body Hyperthermia (LL-WBH) at 40C in Patients With Advanced Malignancies [NCT00004063] | Phase 1/Phase 2 | 30 participants (Anticipated) | Interventional | 1999-08-31 | Recruiting |
| A Phase II Study of High Dose Late Intensification Therapy in Patients With Chemotherapy Sensitive Multiple Myeloma [NCT00004903] | Phase 2 | 0 participants | Interventional | 1999-10-31 | Active, not recruiting |
| PROSPECTIVE CONTROLLED STUDY FOR THE OPTIMIZATION OF THERAPY IN CHRONIC MYELOID LEUKEMIA (CML): MULTICENTRIC STUDY FOR THE EVALUATION OF INTERFERON ALPHA VS ALLOGENIC BM TRANSPLANTATION WITH CHEMOTHERAPY IN CML [NCT00002771] | Phase 3 | 750 participants (Anticipated) | Interventional | 1995-01-31 | Active, not recruiting |
| A Phase 3, Randomized, Open-label, Active-Comparator-Controlled Clinical Study to Evaluate the Safety and Efficacy of Bomedemstat (MK-3543/IMG-7289) Versus Best Available Therapy (BAT) in Participants With Essential Thrombocythemia Who Have an Inadequate [NCT06079879] | Phase 3 | 300 participants (Anticipated) | Interventional | 2023-11-27 | Not yet recruiting |
| A 6-month, Randomized, Active Comparator, Open-label, Multi-Center Study to Evaluate Patient Outcomes, Safety and Tolerability of (Fingolimod) 0.5 mg/Day in Patients With Relapsing Remitting Multiple Sclerosis Who Are Candidates for Multiple Sclerosis (MS [NCT01534182] | Phase 4 | 298 participants (Actual) | Interventional | 2012-01-31 | Completed |
| An Open Trial Combining Zidovudine, Interferon-alfa, and Recombinant CD4-IgG With Transplantation of Syngeneic Bone Marrow and Peripheral Blood Lymphocytes From Healthy gp160-Immunized Donors in the Treatment of Patients With HIV Infection [NCT00000647] | | 6 participants | Interventional | | Completed |
| Phase II Trial of Sequential Modification of Immunosuppression, Interferon Alpha, and Promace-Cytabom For Treatment of Post-Cardiac Transplant Lymphoproliferation. [NCT00002657] | Phase 2 | 20 participants (Actual) | Interventional | 1995-05-31 | Completed |
| A Randomized Phase II Trial of Mitoxantrone, Estramustine and Navelbine or 13-cis Retinoic Acid, Interferon and Paclitaxel in Patients With Metatstatic Hormone Refractory Prostate Cancer [NCT00005847] | Phase 2 | 0 participants | Interventional | 2001-04-05 | Completed |
| A Prospective Randomized Phase III Clinical Trial Assessing the Role of Post-Operative Radiotherapy Plus Adjuvant Interferon Alpha-2b in Patients With Cervical, Axillary, and Inguinal Nodal Metastasis From Cutaneous Melanoma [NCT00003444] | Phase 3 | 167 participants (Anticipated) | Interventional | 1999-03-29 | Completed |
| A Randomized Phase III Trial of Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, IL-2 and Interferon A-2B Versus Cisplatin, Vinblastine, Dacarbazine Alone in Patients With Metastatic Malignant Melanoma [NCT00003027] | Phase 3 | 482 participants (Anticipated) | Interventional | 1997-11-13 | Completed |
| PROSPECTIVE RANDOMISED STUDY TO COMPARE INTERFERON-ALPHA-n1 (WELLFERON) VS 'IDAC' CHEMOTHERAPY AND AUTOGRAFTING FOLLOWED BY INTERFERON ALPHA-n1 (WELLFERON) IN PATIENTS WITH NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOID LEUKEMIA [NCT00002868] | Phase 3 | 744 participants (Anticipated) | Interventional | 1997-11-20 | Completed |
| Biochemotherapy With Temozolomide, Velban, Cisplatin, Interleukin-2, Interferon-alpha and Thalidomide for Metastatic Melanoma With Optional Intrathecal Interleukin-2 Treatment [NCT00505635] | Phase 2 | 5 participants (Actual) | Interventional | 2007-03-31 | Terminated(stopped due to Slow accrual) |
| An Open Label, On-Treatment Trial to Assess the Effect of HIV-1 Coinfection on Therapeutic Responses Using Boceprevir, Peg-Interferon-alfa-2b and Ribavirin in HCV Genotype 1, IFN Treatment-Naive Subjects With or Without HIV-1 [NCT01443923] | Phase 4 | 4 participants (Actual) | Interventional | 2011-09-30 | Terminated(stopped due to Unable to complete enrollment due to newly approved treatment options.) |
| Clinical Trial of Low Dose Oral Interferon Alpha in Idiopathic Pulmonary Fibrosis [NCT01442779] | Phase 2 | 18 participants (Actual) | Interventional | 2000-09-30 | Completed |
| Boceprevir in Community Practice: Assessing Safety, Efficacy, Compliance and Quality of Life, Impact of an Education Program [NCT01405027] | Phase 4 | 197 participants (Actual) | Interventional | 2011-12-31 | Completed |
| A Multi-centre, Open Label, Parallel Group Trial to Evaluate the Pharmacokinetic Interactions Between BI 207127 (600 mg t.i.d. or 600 mg b.i.d.) and BI 201335 (120 mg q.d.) Given in Combination With Ribavirin for 24 Weeks, and Their Combined Effect on the [NCT01525628] | Phase 1 | 72 participants (Actual) | Interventional | 2012-04-30 | Completed |
| A Phase 2B, Randomized Study to Evaluate the Safety and Efficacy of Pegylated Interferon Lambda (BMS-914143) Administered With Ribavirin Plus a Single Direct Antiviral Agent (BMS-790052 or BMS-650032) Versus Pegasys Administered With Ribavirin (Part A) an [NCT01795911] | Phase 2 | 165 participants (Actual) | Interventional | 2013-03-31 | Completed |
| Evaluation of Treatment of Chronic Hepatitis C With Pegylated Interferon and Ribavirin in Patients With/Without Substitution Therapy in Austria [NCT00725751] | | 353 participants (Actual) | Observational | 2007-09-30 | Completed |
| Pilot Phase I/II Study of the Treatment of Classic Central Serous Chorioretinopathy With Topical Interferon Gamma-1b [NCT01468337] | Phase 1/Phase 2 | 5 participants (Actual) | Interventional | 2011-10-31 | Completed |
| Telaprevir in Patients With Genotype 3 HCV: Pilot Clinical Study to Evaluate Efficacy and Predictability of Therapy in Patients Who Have Failed to Respond to Pegylated Interferon and Ribavirin [NCT02087111] | Phase 4 | 14 participants (Actual) | Interventional | 2014-04-30 | Completed |
| A Randomized Trial of the European and American Osteosarcoma Study Group to Optimize Treatment Strategies for Resectable Osteosarcoma Based on Histological Response to Pre-operative Chemotherapy [NCT00134030] | Phase 3 | 1,334 participants (Actual) | Interventional | 2005-11-14 | Completed |
| A Phase II Randomized, Dose Ranging, Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of Different Doses of MK-5172 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Treatment Naïve Subjects With Chronic Hepatiti [NCT01710501] | Phase 2 | 87 participants (Actual) | Interventional | 2012-12-07 | Completed |
| A Randomized, Double-Blind, Crossover Study to Determine the Effect of Actimmune® Dose Titration on the Severity and Incidence of Interferon Gamma-1b-Related Flu-Like Symptoms and the Pattern of Dropouts in Healthy Volunteers [NCT01929382] | Phase 1 | 40 participants (Anticipated) | Interventional | 2013-07-31 | Active, not recruiting |
| Retrospective Cohort to Evaluate the Effectiveness and Safety of Xiyanping Injection Combined With Conventional Treatment for New Coronavirus Infection Pneumonia (Common Type) [NCT04275388] | | 426 participants (Anticipated) | Observational | 2020-05-15 | Not yet recruiting |
| A Multicenter Open-label Study to Evaluate the Safety and Efficacy of PEG-Intron™ Versus PEGASYS™ in Subjects With HBeAg Positive Chronic Hepatitis B and HBeAg Negative Chronic Hepatitis B Protocol No. MK-4031-376-00 (Also Known as SCH 054031, P08450) [NCT01641926] | Phase 3 | 402 participants (Actual) | Interventional | 2012-11-26 | Terminated(stopped due to This study was terminated early due to poor recruitment) |
| Immunotherapy for Autologous/Syngeneic Peripheral Blood Stem Cell (PBSC) Transplant Patients as Treatment for Advanced Multiple Myeloma [NCT00006244] | Phase 2 | 36 participants (Actual) | Interventional | 2000-02-29 | Completed |
| A Prospective, Multicenter, Randomized Controlled Clinical Trial of Pegylated Interferon Alfa-2b Versus Interferon Alfa Therapy in the Treatment of Adult Essential Thrombocythemia [NCT05395507] | Phase 2 | 194 participants (Anticipated) | Interventional | 2022-06-01 | Recruiting |
| A Prospective, Single-center Clinical Trial of Pegylated Interferon Alfa-2b Versus Interferon Alfa Therapy in the Treatment of Childhood and Adolescent Essential Thrombocythemia [NCT04226950] | Phase 2 | 40 participants (Anticipated) | Interventional | 2020-01-10 | Recruiting |
| Phase I Trial of Intravenous Administration of Vesicular Stomatitis Virus Genetically Engineered to Express Thyroidal Sodium Iodide Symporter (NIS) and Human Interferon Beta (hIFNb), in Patients With Metastatic or Recurrent Endometrial Cancer [NCT03120624] | Phase 1 | 77 participants (Anticipated) | Interventional | 2017-09-15 | Recruiting |
| Phase II Study of P1101 in Early Myelofibrosis [NCT02370329] | Phase 2 | 11 participants (Actual) | Interventional | 2015-08-12 | Active, not recruiting |
| A Phase IIa, Randomized, Double-blind (Participant and Investigator Blind, Sponsor Open), Placebo-controlled Trial to Evaluate the Safety, Tolerability, and Antiviral Activity of Oral ACH-0141625 in Combination With Pegylated Interferon Alpha-2a and Ribav [NCT01180790] | Phase 2 | 122 participants (Actual) | Interventional | 2010-09-30 | Completed |
| Double-Blind, Randomized, Placebo-Controlled Study to Assess Safety, Efficacy, and Pharmacokinetics (PK) of GSK2336805 in Combination With Peginterferon and Ribavirin in Treatment-naive Chronic Hepatitis C Subjects With Hepatitis C Virus Genotypes 1 or 4 [NCT01439373] | Phase 2 | 16 participants (Actual) | Interventional | 2011-07-07 | Completed |
| A Multi-Center, Double-Blind, Randomized Study Comparing the Combined Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Patients With Relapsing-Remitting Multiple Sclerosis (CombiRx) [NCT00211887] | Phase 3 | 1,008 participants (Actual) | Interventional | 2005-01-31 | Completed |
| A Randomized, Open-Label Study to Evaluate the Efficacy and Safety of ABT-450/Ritonavir/ABT-267 and ABT-333 Co-administered With and Without Ribavirin Compared to Telaprevir Co-administered With Pegylated Interferon α-2a and Ribavirin in Treatment-Naïve A [NCT01854697] | Phase 3 | 311 participants (Actual) | Interventional | 2013-03-31 | Completed |
| Non-interventional, Observational Study on Retreatment of Chronic Hepatitis C Patients Previous Treatment Failure, Using Peginterferon Alfa-2a and Ribavirin Based Regimens [NCT01798576] | | 282 participants (Actual) | Observational | 2012-11-30 | Terminated |
| An Open-Label Study to Evaluate the Safety, Antiviral Activity and Pharmacokinetics of Direct-Acting Antiviral Agent (DAA) Treatment in Combination With Peginterferon Alpha-2a and Ribavirin (pegIFN/RBV) in Chronic Hepatitis C Virus (HCV) Infected Subjects [NCT01609933] | Phase 2 | 32 participants (Actual) | Interventional | 2012-12-18 | Completed |
| A Phase I/II, Open Clinical Trial to Assess the Safety, Tolerability and Efficacy of a Fixed Dose Combination Therapy of: Hydroxychloroquine (HCQ), Pegylated Interferon Alpha-2a (Peg-IFN Alpha-2a) and Ribavirin (RBV) in Chronic Hepatitis C Genotype 1 Infe [NCT01272310] | Phase 1/Phase 2 | 36 participants (Anticipated) | Interventional | 2011-01-31 | Not yet recruiting |
| A Randomized, Active-Control Phase II Pilot Trial of Bavituximab Combined With Ribavirin for Initial Treatment of Chronic Hepatitis C Virus Genotype 1 Infection [NCT01273948] | Phase 1/Phase 2 | 66 participants (Actual) | Interventional | 2011-01-31 | Completed |
| A Phase IIb, Open Label, Single Arm, Multicenter Study to Evaluate the Effect of 48-weeks PEG-Interferon Alfa-2a (PEG-IFN) Administration on Serum HBsAg in Chronic Hepatitis B, HBeAg-Negative, Genotype D Patients on Treatment With Nucleos(t)Ide Analogues [NCT01706575] | Phase 2 | 76 participants (Actual) | Interventional | 2013-01-31 | Completed |
| A Pilot Study to Test Whether Systemic Interferon Gamma Increases Tumor Class I MHC Expression in Patients With Synovial Sarcoma and Myxoid/Round Cell Liposarcoma [NCT01957709] | Early Phase 1 | 8 participants (Actual) | Interventional | 2013-09-25 | Terminated(stopped due to Enough samples were collected for data analysis.) |
| A Phase 1/2 Trial Evaluating αDC1 Vaccines Combined With Tumor-Selective Chemokine Modulation as Adjuvant Therapy After Surgical Resection of Peritoneal Surface Malignancies [NCT02151448] | Phase 1/Phase 2 | 64 participants (Actual) | Interventional | 2014-07-31 | Completed |
| Response-guided Triple-therapy Using Boceprevir in Combination With PEGIFN/RBV in HIV/HCV-coinfected Patients [NCT01925183] | Phase 4 | 6 participants (Actual) | Interventional | 2013-08-31 | Completed |
| A Phase IIa, Open-label Trial to Evaluate the Safety, Tolerability and Efficacy of a 12 Weeks Combination Therapy of TMC647055 and TMC435 With and Without GSK23336805 With a Pharmacokinetic Enhancer With and Without Ribavirin in Chronic Genotype 1 Hepatit [NCT01724086] | Phase 2 | 90 participants (Actual) | Interventional | 2012-10-31 | Completed |
| A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Twice-Weekly Peginterferon Alpha 2a and Ribavirin Induction Therapy for Chronic Hepatitis C in Patients Who Are Coinfected With HIV-1 [NCT00085917] | Phase 2 | 29 participants (Actual) | Interventional | 2004-06-30 | Completed |
| PEG IFN-alpha2a (Pegasys®) Therapy in Patients With Chronic Myeloproliferative Diseases (Excluding Philadelphia Chromosome Positive Chronic Myeloid Leukemia) [NCT00452023] | Phase 2 | 84 participants (Actual) | Interventional | 2005-04-07 | Completed |
| Prospective, Observational Study of Predictors of the Effectiveness of Pegylated Interferon in a Cohort of Patients With Hepatitis C in Georgia [NCT01659567] | | 516 participants (Actual) | Observational | 2011-04-06 | Completed |
| Phase II Study of Dexamethasone/Alpha-Interferon in AL Amyloidosis [NCT00002849] | Phase 2 | 93 participants (Actual) | Interventional | 1996-11-30 | Completed |
| Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Alpha Interferon (IFN-A), Low-Dose Cytosine Arabinoside (ARA-C), and Homoharringtonine (HHT) [NCT00003239] | Phase 2 | 90 participants (Actual) | Interventional | 1998-03-31 | Completed |
| Phase I Combined Modality Protocol for Malignant Mesothelioma: Cisplatin & rIFN-alpha-2b Followed by Surgical Resection (Debulking), and Post-Op Concurrent Chemoradiotherapy With Cisplatin, +/- rIFN-alpha-2b [NCT00003263] | Phase 1 | 6 participants (Actual) | Interventional | 1996-08-31 | Completed |
| ProspeCtive Study to Evaluate Efficacy, Safety and tOlerability of Dietary supplemeNT of Curcumin (BCM95) in Subjects With Active Relapsing MultIple Sclerosis Treated With subcutaNeous Interferon Beta 1a 44 mcg Three Times a Week (TIW) [NCT01514370] | Phase 2 | 80 participants (Actual) | Interventional | 2012-04-30 | Completed |
| Phase 3 Open Label Study Evaluating the Efficacy and Safety of Pegylated Interferon Lambda-1a, in Combination With Ribavirin and Daclatasvir, for Treatment of Chronic HCV Infection With Treatment naïve Genotypes 1, 2, 3 or 4 in Subjects Co-infected With H [NCT01866930] | Phase 3 | 453 participants (Actual) | Interventional | 2013-07-11 | Terminated(stopped due to Sponsor decision not based on any new unexpected safety findings or efficacy observations.) |
| Type 1 Interferon as a Mucosal Adjuvant for Influenza Vaccine Given Intranasally [NCT00436046] | Phase 1 | 95 participants (Actual) | Interventional | 2007-03-31 | Completed |
| A Multicentre, Prospective, Randomized Open-label Pilot Study to Assess the Feasibility and Preliminary Efficacy of Interferon-gamma in Combination With Anidulafungin for the Treatment of Candidemia [NCT01270490] | Phase 3 | 20 participants (Anticipated) | Interventional | 2011-01-31 | Recruiting |
| A Multicenter, Prospective Non-interventional Study to Evaluate the Quality of Life in Belgian Patients With CIS or RRMS in Whom Interferon Beta-1a IM Treatment Has Been Initiated [NCT01272128] | | 100 participants (Actual) | Observational | 2012-12-31 | Completed |
| A Placebo-Controlled, Multicenter, Double-Blind, Randomized Trial of Pegylated Interferon Plus Ribavirin With or Without CTS-1027 in HCV Null-Responders [NCT01273064] | Phase 2 | 114 participants (Actual) | Interventional | 2011-01-31 | Terminated(stopped due to Risk-benefit ratio) |
| A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex [NCT01864148] | Phase 2 | 419 participants (Actual) | Interventional | 2013-08-31 | Completed |
| A Real-World Study of Sequential Combination Therapy With Pegylated Interferon In Nucleoside-treated Patients With Chronic Hepatitis B [NCT03357822] | Phase 4 | 2,000 participants (Anticipated) | Interventional | 2018-01-25 | Recruiting |
| Subcutaneous (SC) Interferon Beta Therapy in Multiple Sclerosis Patients and Characterization of Injection Site Reactions and Flu-Like Symptoms Under Daily Practice Setting [NCT03347370] | | 626 participants (Actual) | Observational | 2017-11-27 | Completed |
| Mechanism of Action of Ocrelizumab in Multiple Sclerosis [NCT03344094] | | 30 participants (Anticipated) | Observational | 2017-10-12 | Recruiting |
| Human Recombinant Interferon Gamma in the Treatment of Ventilator-acquired Pneumonia in ICU Patients [NCT05843786] | Phase 3 | 132 participants (Anticipated) | Interventional | 2023-06-30 | Recruiting |
| A Phase 3 Clinical Trial to Study Short Duration Versus Standard Response-Guided Therapy With MK-3034 (SCH 503034)/Boceprevir Combined With PegIntron and Ribavirin in Previously Untreated Non-Cirrhotic Subjects With Chronic HCV Genotype 1 in Asia [NCT01945294] | Phase 3 | 257 participants (Actual) | Interventional | 2013-10-10 | Completed |
| Open-label, Multicenter, Trial Evaluating Efficacy and Safety of Peginterferon Alfa-2a (PEGASYS®) in Patients With Chronic Hepatitis D (CHD) [NCT02732639] | Phase 3 | 31 participants (Actual) | Interventional | 2005-10-31 | Completed |
| Evaluate the Pharmacokinetic and Pharmacodynamic Profile, Safety, and Tolerability of Escalating Single Dose & Multiple Dose by Using Recombinant Human Serum Albumin/Interferon alpha2b Fusion Protein in Hepatitits B Patients [NCT03294798] | Phase 1/Phase 2 | 11 participants (Actual) | Interventional | 2017-06-13 | Completed |
| Phase II Study of Recombinant Anti-tumor and Anti-virus Protein for Injection to Treat Advanced Neuroendocrine Tumors [NCT02455596] | Phase 2 | 20 participants (Anticipated) | Interventional | 2015-05-31 | Recruiting |
| An Open-Label, Phase 4 Study of Telaprevir, Peginterferon Alfa-2a (Pegasys®), and Ribavirin (Copegus®) in Treatment-Experienced Black/African American and Non-Black/African American Subjects With Genotype 1 Chronic Hepatitis C Who Have Not Achieved a Sust [NCT01467492] | Phase 4 | 121 participants (Actual) | Interventional | 2012-01-31 | Terminated(stopped due to It was decided by Sponsor on 13 January 2014 to terminate study early at primary efficacy endpoint as part of a decision to modify drug development plan.) |
| PROmyBETAapp: Ascertaining Medication Usage & Documentation of Patient Reported Outcomes Utilizing the myBETAapp® in Patients With Multiple Sclerosis Treated With Betaferon®: a Pilot Study [NCT03134573] | | 96 participants (Actual) | Observational | 2017-09-15 | Completed |
| "Medical Treatment of High-Risk Neurofibromas in Patients With Type 1 Neurofibromatosis: A Clinical Trial of Sequential Medical Therapies" [NCT00846430] | Phase 2 | 9 participants (Actual) | Interventional | 2008-10-31 | Completed |
| An Open Prospective Observational Study Evaluating the Efficacy and Tolerability of Interferon Gamma (Ingaron) Injections in Patients With Drug-resistant Pulmonary Tuberculosis [NCT05359315] | | 84 participants (Anticipated) | Observational | 2022-04-15 | Recruiting |
| A Trial of Prednisone and Acetaminophen Versus Acetaminophen Alone in Minimizing Flu-like Symptoms From Pegylated Interferon Beta-1a [NCT03424733] | Phase 4 | 50 participants (Anticipated) | Interventional | 2017-09-25 | Recruiting |
| Phase I/II Study of Anti-PD-1/PD-L1 Antibodies Combined With Pegylated Interferon Alfa-2b in Patients With Advanced-Stage Hepatocellular Carcinoma [NCT04943679] | | 15 participants (Anticipated) | Observational | 2021-06-15 | Recruiting |
| A Phase 2 Multicenter, Randomized, Open-label Study to Investigate the Efficacy and Safety of BRII-835 (VIR-2218) and Pegylated Interferon Alpha (PEG-IFNα) Combination Therapy for the Treatment of Chronic Hepatitis B Virus (HBV) Infection [NCT05970289] | Phase 2 | 75 participants (Anticipated) | Interventional | 2023-08-22 | Recruiting |
| Phase 3, Randomized, Open-Label, Parallel Arm Study to Evaluate the Efficacy and Safety of 180 mcg Peginterferon Lambda-1a (Lambda) Subcutaneous Injection for 48 Weeks in Patients With Chronic Hepatitis Delta Virus (HDV) Infection (LIMT-2) [NCT05070364] | Phase 3 | 150 participants (Anticipated) | Interventional | 2021-12-21 | Active, not recruiting |
| Study of the Safety and Efficacy of Sofosbuvir-Based Regimens in the Treatment of Egyptian Patients With and Without Post-hepatitis C Cirrhosis [NCT02992457] | Phase 4 | 10,000 participants (Actual) | Interventional | 2015-01-31 | Completed |
| A Phase 3, Safety and Efficacy Study of Boceprevir/Peginterferon Alfa-2a/Ribavirin in Chronic HCV Genotype 1 IL28B CC Subjects [NCT01544920] | Phase 3 | 737 participants (Actual) | Interventional | 2012-05-30 | Completed |
| A Phase III Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of TMC435 Plus PegIFNα-2a (Pegasys) and Ribavirin (Copegus) Triple Therapy in Chronic Hepatitis C Genotype-1 Infected Subjects Who Are Co-infected With Human Immunodeficiency V [NCT01479868] | Phase 3 | 109 participants (Actual) | Interventional | 2011-10-31 | Completed |
| A Phase I/II Study of the SV-BR-1-GM Regimen in HLA Matched Metastatic Breast Cancer Patients in Combination With Pembrolizumab [NCT04418219] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2020-12-21 | Withdrawn(stopped due to Funding Discontinued) |
| A Phase II Study of Type-1 Polarized Dendritic Cell (aDC1) -Based Treatment in Combination With Tumor-Selective Chemokine Modulation (CKM: Interferon Alpha 2b, Rintatolimod and Celecoxib) in Melanoma Patients With Primary PD-1/PD-L1 Resistance [NCT04093323] | Phase 2 | 24 participants (Anticipated) | Interventional | 2023-12-31 | Suspended(stopped due to IFNa2b supply shortage) |
| Telaprevir in Combination With Standard of Care in Hepatitis C Genotype 1 Infection in Patients With Hepatocellular Carcinoma Awaiting Liver Transplantation [NCT01821963] | Phase 3 | 1 participants (Actual) | Interventional | 2013-04-30 | Terminated(stopped due to Low referral rate due to new therapeutic options.) |
| A Phase 3 Evaluation of BMS-790052 in Combination With Peg-Interferon Alfa-2a and Ribavirin in Treatment Naive Subjects With Chronic Hepatitis C Genotype 4 [NCT01448044] | Phase 3 | 152 participants (Actual) | Interventional | 2011-12-31 | Completed |
| A I//II Phase Study of the Efficacy and Safety of Interferon-Gamma by Subcutaneous Injection in the Complex Treatment of Patients Infected With HIV and Tuberculosis [NCT05065905] | Phase 1/Phase 2 | 78 participants (Actual) | Interventional | 2006-01-19 | Completed |
| Interferon-α Prevents Leukemia Relapse of AML Patients Undergoing HLA-identical Allogeneic Hematopoietic Stem Cell Transplantation With Pretransplant MRD [NCT03121079] | | 0 participants (Actual) | Interventional | 2017-05-01 | Withdrawn(stopped due to there was almost no patient would enroll in this study.) |
| Early Diagnosis of Active Tuberculosis Using Ultra Low-dose Chest CT to Predict Progression to Active Tuberculosis Among Contacts [NCT03220464] | | 116 participants (Anticipated) | Interventional | 2017-06-20 | Recruiting |
| Pegylated Interferon +/- Ribavirin for Children With Hepatitis C [NCT00100659] | Phase 3 | 114 participants (Actual) | Interventional | 2004-12-31 | Completed |
| Host Response to Tuberculosis and Acquired Immune Deficiency Syndrome [NCT00201123] | Phase 2 | 89 participants (Actual) | Interventional | 2005-04-30 | Completed |
| An Open-Label Study to Assess the Immune Response to Vaccination in Tecfidera® (BG00012)-Treated Versus Interferon-Treated Subjects With Relapsing Forms of Multiple Sclerosis. [NCT02097849] | Phase 2 | 71 participants (Actual) | Interventional | 2015-02-28 | Completed |
| Phase II Trial of Chemoimmunotherapy With 5-Fluorouracil Followed by Interferon-alfa-2b in Previously-treated Metastatic Gastrointestinal, Kidney, or Lung Cancer [NCT01658813] | Phase 2 | 18 participants (Actual) | Interventional | 2012-07-31 | Completed |
| Response to Peg-interferon and Ribavirin for the Treatment of HCV Infection in HIV Co-infected Patients, Implemented in Public Hospitals in Thailand [NCT02247440] | Phase 4 | 18 participants (Actual) | Interventional | 2014-08-31 | Completed |
| A Phase II Study of Pegylated Interferon Alfa-2b in AJCC Stage III (TxN1-2M0) Melanoma Subjects After Regional Lymph Node Dissection in Russia [NCT02155322] | Phase 2 | 33 participants (Actual) | Interventional | 2014-08-19 | Completed |
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] |
| Trial | Outcome |
|---|
| NCT00003641 (2) [back to overview] | 5-year Relapse-free Survival Rate |
| NCT00003641 (2) [back to overview] | 5-year Overall Survival Rate |
| NCT00003656 (4) [back to overview] | Best Response as Measured by CT, Bone Scans, and Clinical Progression |
| NCT00003656 (4) [back to overview] | Number of Subjects With Toxicity by Clinical Evaluation From First Dose to 30 Days After Last Dose |
| NCT00003656 (4) [back to overview] | Duration of Response (Progression-free Survival) as Measured by CT, Bone Scans, and Clinical Progression From Initiation of Therapy Until an Increase of ≥ 25% From the Smallest Sum of All Tumor Measurements Obtained During the Best Response |
| NCT00003656 (4) [back to overview] | Change in Retinoic Acid Receptor Expression on Tissue as Measured by Number of Subjects With the Presence of Peripheral Blood Lymphocytes During the First and Fifth Dose |
| NCT00004088 (2) [back to overview] | Three-year Overall Survival |
| NCT00004088 (2) [back to overview] | Progression-free Survival |
| NCT00006237 (3) [back to overview] | Toxicity |
| NCT00006237 (3) [back to overview] | 5-year Relapse-Free Survival |
| NCT00006237 (3) [back to overview] | 5-year Overall Survival |
| NCT00006244 (6) [back to overview] | Number of Patients <56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity |
| NCT00006244 (6) [back to overview] | Initial Response to Therapy |
| NCT00006244 (6) [back to overview] | Overall Survival |
| NCT00006244 (6) [back to overview] | Number of Patients ≥56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity |
| NCT00006244 (6) [back to overview] | Proportion of Patients Alive and in Remission |
| NCT00006244 (6) [back to overview] | Time to Disease Progression |
| NCT00015847 (3) [back to overview] | Major Cytogenetic Response After 6 and 12 Months of Treatment. |
| NCT00015847 (3) [back to overview] | Treatment-related Toxicity (i.e., Grade 3 or 4 Nonhematologic Toxicity) as Measured by NCI CTCAE v3.0 (Phase I) |
| NCT00015847 (3) [back to overview] | Complete Cytogenetic Response at 6 and 12 Months (Phase II) |
| NCT00026221 (3) [back to overview] | Comparison of Plasma Levels of VEGF Following Administration of Bevacizumab Alone or in Combination With IFN-alfa |
| NCT00026221 (3) [back to overview] | Objective Response Rate |
| NCT00026221 (3) [back to overview] | Progression-free Survival |
| NCT00036569 (5) [back to overview] | Two Year Survival of Pediatric Patients With Diffuse Pontine Gliomas |
| NCT00036569 (5) [back to overview] | Number of Participants With Adverse Events |
| NCT00036569 (5) [back to overview] | Number of Participants With a Metabolic and Biological Change in the Brainstem Through Magnetic Resonance Imaging (MRI) Techniques |
| NCT00036569 (5) [back to overview] | Median Time to Progression |
| NCT00036569 (5) [back to overview] | Mean Quality of Life (QOL) Score at Baseline and Follow-Up |
| NCT00047879 (1) [back to overview] | The Number of Participants With Adverse Events |
| NCT00049530 (4) [back to overview] | Non-progression Rate (Clinical Response to Peginterferon Alfa-2b) |
| NCT00049530 (4) [back to overview] | Progression Free Survival |
| NCT00049530 (4) [back to overview] | Plasma b-FGF Level Response |
| NCT00049530 (4) [back to overview] | Overall Survival |
| NCT00050778 (5) [back to overview] | Annualized Relapse Rate |
| NCT00050778 (5) [back to overview] | Percent Change From Baseline in MRI T2 Lesion Volume at Year 3 |
| NCT00050778 (5) [back to overview] | Percent Change From Baseline in T1 Cerebral Volume at Year 3 |
| NCT00050778 (5) [back to overview] | Probability of Participants Who Were Relapse Free at 3 Years After Initial Treatment |
| NCT00050778 (5) [back to overview] | Probability of Participants With Sustained Accumulation of Disability (SAD) |
| NCT00062010 (3) [back to overview] | Progression-free Survival |
| NCT00062010 (3) [back to overview] | Survival |
| NCT00062010 (3) [back to overview] | Response by RECIST Criteria (v 1.0) |
| NCT00065468 (8) [back to overview] | Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) |
| NCT00065468 (8) [back to overview] | Time to Treatment Failure (TTF) |
| NCT00065468 (8) [back to overview] | European Quality of Life Health Questionnaire (EQ-5D) - Index Score |
| NCT00065468 (8) [back to overview] | Duration of Response (DR) |
| NCT00065468 (8) [back to overview] | Overall Survival (OS) |
| NCT00065468 (8) [back to overview] | Percentage of Participants With Clinical Benefit |
| NCT00065468 (8) [back to overview] | Percentage of Participants With Objective Response |
| NCT00065468 (8) [back to overview] | Progression-Free Survival (PFS) |
| NCT00068575 (1) [back to overview] | Median Overall Survival (OS) |
| NCT00078338 (1) [back to overview] | Time to First Relapse |
| NCT00083551 (1) [back to overview] | Overall Survival |
| NCT00083889 (24) [back to overview] | Plasma Concentrations of Soluble Proteins: Plasma Basic Fibroblast Growth Factor (bFGF) That May be Associated With Tumor Proliferation or Angiogenesis |
| NCT00083889 (24) [back to overview] | Functional Assessment of Cancer Therapy-General (FACT-G): Social/Family Well Being (SWB) Subscale |
| NCT00083889 (24) [back to overview] | Functional Assessment of Cancer Therapy-General (FACT-G): Physical Well Being (PWB) Subscale |
| NCT00083889 (24) [back to overview] | Ctrough Concentrations of Metabolite SU012662 |
| NCT00083889 (24) [back to overview] | Functional Assessment of Cancer Therapy-General (FACT-G): Functional Well Being (FWB) Subscale |
| NCT00083889 (24) [back to overview] | Time to Tumor Progression (TTP), Investigator's Assessment |
| NCT00083889 (24) [back to overview] | Functional Assessment of Cancer Therapy-General (FACT-G): Emotional Well Being (EWB) Subscale |
| NCT00083889 (24) [back to overview] | Functional Assessment of Cancer Therapy-General (FACT-G) |
| NCT00083889 (24) [back to overview] | FACT-Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Subscale |
| NCT00083889 (24) [back to overview] | FACT-Kidney Symptom Index (FKSI) Subscale |
| NCT00083889 (24) [back to overview] | EuroQoL Five Dimension (EQ-5D) Health State Index |
| NCT00083889 (24) [back to overview] | Euro-QoL Visual Analog Scale (EQ-VAS) |
| NCT00083889 (24) [back to overview] | Ctrough Concentrations of SU011248 and Active Metabolite SU012662 |
| NCT00083889 (24) [back to overview] | Ctrough Concentrations of SU011248 |
| NCT00083889 (24) [back to overview] | Plasma Concentrations of Soluble Proteins: Plasma VEGF-A, Plasma VEGF-C, Plasma sVEGFR-3, PLASMA IL-8, and PLASMA bFGF That May be Associated With Tumor Proliferation or Angiogenesis |
| NCT00083889 (24) [back to overview] | Time to Tumor Progression (TTP), Core Radiology Assessment |
| NCT00083889 (24) [back to overview] | Duration of Response (DR), Core Radiology Assessement |
| NCT00083889 (24) [back to overview] | Duration of Response (DR), Investigator's Assessment |
| NCT00083889 (24) [back to overview] | Incremental Cost Effectiveness Ratio (ICER) |
| NCT00083889 (24) [back to overview] | Objective Response, Core Radiology Assessment |
| NCT00083889 (24) [back to overview] | Objective Response, Investigator's Assessment |
| NCT00083889 (24) [back to overview] | Overall Survival (OS) |
| NCT00083889 (24) [back to overview] | Progression-Free Survival (PFS), Core Radiology Assessment |
| NCT00083889 (24) [back to overview] | Progression-Free Survival (PFS), Investigator's Assessment |
| NCT00085436 (2) [back to overview] | Clinical Response as Measured by RECIST |
| NCT00085436 (2) [back to overview] | Immunity as Measured by T-cell and Antibody Responses to the Tumor |
| NCT00085917 (3) [back to overview] | Number of Participants With Sustained Virologic Response (SVR) |
| NCT00085917 (3) [back to overview] | Number of Participants With Normalization of Liver Enzymes |
| NCT00085917 (3) [back to overview] | Number of Participants With Adverse Events |
| NCT00100659 (2) [back to overview] | Adverse Events |
| NCT00100659 (2) [back to overview] | Sustained Viral Response (SVR) |
| NCT00110396 (3) [back to overview] | Number of Participants Who Were Neutralising Antibody (NAb) Positive at Anytime During the Study |
| NCT00110396 (3) [back to overview] | Number of Participants With Binding Antibodies (BAb) at Week 96 |
| NCT00110396 (3) [back to overview] | Number of Participants Who Were Neutralising Antibody (NAb) Positive at the Week 96 Visit. |
| NCT00117637 (34) [back to overview] | Average of All Trough Plasma Concentrations |
| NCT00117637 (34) [back to overview] | Duration of Response According to the Independent Radiological Review for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Duration of Response According to the Investigator Assessment for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Duration of Response According to the Investigator Assessment for the Second Intervention Period |
| NCT00117637 (34) [back to overview] | Overall Survival (OS) |
| NCT00117637 (34) [back to overview] | Progression Free Survival According to the Investigator Assessment (Second Intervention Period) |
| NCT00117637 (34) [back to overview] | Progression-free Survival (PFS) Based on Independent Radiological Review for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Progression-free Survival (PFS) Based on Investigator Assessment for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Slope - Change in Trough Concentration/Cycle |
| NCT00117637 (34) [back to overview] | Time to Response According to the Investigator Assessment for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Time to Response According to the Investigator Assessment for the Second Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period |
| NCT00117637 (34) [back to overview] | Disease Control (DC) According to Independent Central Review for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Disease Control (DC) According to the Investigator Assessment for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period |
| NCT00117637 (34) [back to overview] | Tumor Response According to the Independent Radiological Review for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Tumor Response According to the Investigator Assessment for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Tumor Response According to the Investigator Assessment for the Second Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Time to Response According to the Independent Radiological Review for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the Second Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) After Intervention for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period |
| NCT00117637 (34) [back to overview] | Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period |
| NCT00126594 (6) [back to overview] | Duration of Response for Participants With Stable Disease (N=37) Following Treatment |
| NCT00126594 (6) [back to overview] | Objective Response Rate (ORR) Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00126594 (6) [back to overview] | Progression-free Survival |
| NCT00126594 (6) [back to overview] | Best Overall Response for Participants |
| NCT00126594 (6) [back to overview] | Selected Grade 3-4 Adverse Events Using NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 |
| NCT00126594 (6) [back to overview] | Median Overall Survival (OS) |
| NCT00134030 (3) [back to overview] | Percentage of Patients With Overall Survival |
| NCT00134030 (3) [back to overview] | Event-free Survival (EFS) |
| NCT00134030 (3) [back to overview] | Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 |
| NCT00179413 (3) [back to overview] | Determination of the Effect of PEG-Intron 0.5mg Per kg Weekly sc Versus Colchicine 0.6mg Bid Daily on: |
| NCT00179413 (3) [back to overview] | Development of Portal Hypertension |
| NCT00179413 (3) [back to overview] | Evaluation of Safety and Tolerability of Long Term Maintenance PEG-Intron in Patients With Cirrhosis |
| NCT00179478 (4) [back to overview] | Annualized Relapse Rate |
| NCT00179478 (4) [back to overview] | Rate of Development of Clinical Definite Multiple Sclerosis (CDMS) Over 10 Years |
| NCT00179478 (4) [back to overview] | The Number of New or Enlarging MRI T2 Lesions at 10 Years |
| NCT00179478 (4) [back to overview] | Number of Participants With an EDSS > 3.5 at Study Completion |
| NCT00185211 (11) [back to overview] | Time to Confirmed Expanded Disability Status Scale (EDSS) Progression Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With Confirmed EDSS Progression at Selected Points in Time |
| NCT00185211 (11) [back to overview] | Time to Clinically Definite Multiple Sclerosis (CDMS) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS at Selected Points in Time |
| NCT00185211 (11) [back to overview] | Relapse-based Efficacy Domain: Time to Multiple Sclerosis (MS) According to McDonald Criteria |
| NCT00185211 (11) [back to overview] | Relapse-based Efficacy Domain: Hazard Ratio for Recurrent Relapses |
| NCT00185211 (11) [back to overview] | Relapse-based Efficacy Domain (Supportive): Annualized Relapse Rate |
| NCT00185211 (11) [back to overview] | MRI-based Efficacy Domain: Percentage Change of Brain Volume From Screening MRI to Month 60 |
| NCT00185211 (11) [back to overview] | MRI-based Efficacy Domain: Absolute Change of Volume of Black Holes From Screening MRI to Month 60 |
| NCT00185211 (11) [back to overview] | Disability-based Efficacy Domain: Multiple Sclerosis Functional Composite (MSFC) at Month 60 |
| NCT00185211 (11) [back to overview] | MRI-based Efficacy Domain: Absolute Change of T2 Lesion Volume From Screening MRI to Month 60 |
| NCT00185211 (11) [back to overview] | MRI (Magnet-Resonance Imaging)-Based Efficacy Domain: Cumulative Number of Newly Active Lesions at Month 60 |
| NCT00185211 (11) [back to overview] | Functional Assessment of Multiple Sclerosis (FAMS) Trial Outcome Index (TOI) at Month 60 |
| NCT00201123 (3) [back to overview] | Chest Cavity Size |
| NCT00201123 (3) [back to overview] | Sputum Conversion |
| NCT00201123 (3) [back to overview] | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels |
| NCT00211692 (4) [back to overview] | Participants Achieving SVR Categorized by Time of Response |
| NCT00211692 (4) [back to overview] | The Primary Endpoint Would be the Number Who Achieve a Sustained Virologic Response. |
| NCT00211692 (4) [back to overview] | Overall Number of Serious Adverse Events |
| NCT00211692 (4) [back to overview] | Number of Participants Discontinuing Early From Study Treatment |
| NCT00211887 (4) [back to overview] | Change in MRI Composite Score |
| NCT00211887 (4) [back to overview] | ARR - PDEs |
| NCT00211887 (4) [back to overview] | Change in the Multiple Sclerosis Functional Composite |
| NCT00211887 (4) [back to overview] | Confirmed Progression on the Expanded Disability Status Scale |
| NCT00235989 (2) [back to overview] | Safety and Tolerability as Defined by the Number of Subjects With Flu-like Syndrome, Fever, Myalgia, Injection Site Reactions, Injection Site Reactions Pain, Asthenia, Headache, Liver Function Abnormalities, and Bone Marrow Function Abnormalities |
| NCT00235989 (2) [back to overview] | Frequency (Number of Patients Per Group Defined by Cut Off Values and Per Treatment Arm) of Neutralizing Antibody (NAb) Titer to IFNB-1b |
| NCT00246324 (2) [back to overview] | Gadolinium-enhancing (Gd+)Lesion Number Change. |
| NCT00246324 (2) [back to overview] | Relapse Rates, Serum Matrix Metalloproteinase 9 Levels, Transendothelial Migration of Monocytes |
| NCT00262951 (2) [back to overview] | Number of Patients in Whom Tumor Was Resectable |
| NCT00262951 (2) [back to overview] | Overall Survival |
| NCT00265395 (1) [back to overview] | Sustained Virologic Response, Defined as a Plasma HCV-RNA (Hepatitis C Ribonucleic Acid) Level Below the LLQ (Lower Level of Quantitation) at 24 Weeks Post-treatment. |
| NCT00333840 (10) [back to overview] | Percentage of Participants With Best Cytogenetic Response (Second-line Treatment) |
| NCT00333840 (10) [back to overview] | Kaplan-Meier Estimates of Overall Survival (All Randomized Participants) |
| NCT00333840 (10) [back to overview] | Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants) |
| NCT00333840 (10) [back to overview] | Kaplan Meier Estimates of Event Free Survival (All Randomized Participants) |
| NCT00333840 (10) [back to overview] | Number of Participants With Serious Adverse Events as a Measure of Safety (Second-line Treatment) |
| NCT00333840 (10) [back to overview] | Percentage of Participants With Best Cytogenetic Response (First-line Treatment) |
| NCT00333840 (10) [back to overview] | Number of Participants With Serious Adverse Events as a Measure of Safety (First-line Treatment) |
| NCT00333840 (10) [back to overview] | Percentage of Participants With Major Molecular Response (Second-line Treatment) |
| NCT00333840 (10) [back to overview] | Percentage of Participants With Major Molecular Response (First-line Treatment) |
| NCT00333840 (10) [back to overview] | Percentage of Participants With Event Free Survival Events (All Randomized Participants) |
| NCT00336479 (5) [back to overview] | Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing |
| NCT00336479 (5) [back to overview] | Number of Subjects With Viral Relapse |
| NCT00336479 (5) [back to overview] | Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir |
| NCT00336479 (5) [back to overview] | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT00336479 (5) [back to overview] | Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing |
| NCT00340834 (6) [back to overview] | Percentage of Participants Free of 3-month and 6-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Extension Phase of the Study |
| NCT00340834 (6) [back to overview] | Number of New or Newly Enlarged T2 Lesions in Comparison With Baseline in the Core Phase of the Study |
| NCT00340834 (6) [back to overview] | Estimated Annualized Aggregate Relapse Rate (ARR) in the Core Phase of the Study |
| NCT00340834 (6) [back to overview] | Number of New or Newly Enlarged T2 Lesions in the Extension Phase of the Study |
| NCT00340834 (6) [back to overview] | Percentage of Participants Free of 3-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Core Phase of the Study |
| NCT00340834 (6) [back to overview] | Estimated Annualized Aggregate Relapse Rate (ARR) in the Core and Extension Phases of the Study |
| NCT00363649 (5) [back to overview] | Disease-free Survival |
| NCT00363649 (5) [back to overview] | Early Discontinuation |
| NCT00363649 (5) [back to overview] | Progression-free Survival |
| NCT00363649 (5) [back to overview] | Time to Complete Molecular Remission |
| NCT00363649 (5) [back to overview] | Complete Remission Rate |
| NCT00367484 (1) [back to overview] | Number of Participants Testing Positive for Neutralising Antibody (NAb) |
| NCT00370071 (12) [back to overview] | Expanded Disability Status Scale (EDSS) |
| NCT00370071 (12) [back to overview] | Assessment of Relapses: Relapse Severity |
| NCT00370071 (12) [back to overview] | Assessment of Relapses: Number of Relapses |
| NCT00370071 (12) [back to overview] | Percentage of Subjects Without EDSS Progression |
| NCT00370071 (12) [back to overview] | Difference Between the Number of New or Enlarging T2 Lesions Per 3 Months During the 6-month Treatment Period and the Number of New or Enlarging T2 Lesions During 3-month Pre-treatment |
| NCT00370071 (12) [back to overview] | Volume of Gadolinium-enhancing Lesions at Baseline, Weeks 12 and 24 |
| NCT00370071 (12) [back to overview] | Difference Between the Number of New Gadolinium (Gd)-Enhancing Lesions Per 3 Months During the 6-month Treatment Period and the Number of New Gd-enhancing Lesions During 3-month Pre-treatment |
| NCT00370071 (12) [back to overview] | Assessment of Relapses: Relapse Rate |
| NCT00370071 (12) [back to overview] | Assessment of Relapses: Percentage of Relapse-free Subjects After 24 Weeks |
| NCT00370071 (12) [back to overview] | Number of New Gadolinium (T1)-Enhancing Lesions at Baseline, Weeks 12 and 24 |
| NCT00370071 (12) [back to overview] | Number of T2 Lesions at Baseline, Weeks 12 and 24 |
| NCT00370071 (12) [back to overview] | Difference Between the Number of Newly Active Lesions in Magnetic Resonance Imaging (MRI) Per Three Months During the 6-month Treatment Period and the Number of Newly Active Lesions During 3-month Pre-treatment |
| NCT00371761 (1) [back to overview] | Number of Participants With a Combined Response Consisting of All Three Responses - (a) Serological Response, (b) Virological Response, and (c) Biochemical Response |
| NCT00372385 (6) [back to overview] | Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir |
| NCT00372385 (6) [back to overview] | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT00372385 (6) [back to overview] | Number of Subjects With Viral Relapse |
| NCT00372385 (6) [back to overview] | Percentage of Subjects With Undetectable Plasma HCV RNA at Completion of Study Drug Dosing |
| NCT00372385 (6) [back to overview] | Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing |
| NCT00372385 (6) [back to overview] | Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing |
| NCT00378599 (1) [back to overview] | A Sustained Virologic Response (SVR), Defined as a Plasma HCV RNA Level Below the Lower Level of Quantitation (LLQ) at 24 Weeks Post-treatment |
| NCT00420784 (6) [back to overview] | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT00420784 (6) [back to overview] | Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir |
| NCT00420784 (6) [back to overview] | Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing |
| NCT00420784 (6) [back to overview] | Percentage of Subjects With Undetectable Plasma HCV RNA at Completion of Study Drug Dosing |
| NCT00420784 (6) [back to overview] | Percentage of Subjects With Undetectable Plasma HCV RNA |
| NCT00420784 (6) [back to overview] | Number of Subjects With Viral Relapse |
| NCT00423800 (2) [back to overview] | Number of Participants With a Sustained Virologic Response |
| NCT00423800 (2) [back to overview] | Number of Participants With a Virological Relapse |
| NCT00428584 (10) [back to overview] | Diameter of Injection Site Redness |
| NCT00428584 (10) [back to overview] | Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and 10 Minutes Post-injection Timepoints |
| NCT00428584 (10) [back to overview] | Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and Immediately After Injection Timepoints |
| NCT00428584 (10) [back to overview] | Secondary Outcome - Extension Phase: Change in Mean (mm) VAS for Pre-injection and Immediately After Injection Timepoints |
| NCT00428584 (10) [back to overview] | Secondary Outcome - Extension Phase: Change in Mean VAS at Pre-injection and 10 Minutes Post Injection |
| NCT00428584 (10) [back to overview] | Number of Pain Free Patients at 30 Minutes Post-injection |
| NCT00428584 (10) [back to overview] | Primary Outcome - Extension Phase: Visual Analog Scale (VAS) of Patients Reported Pain; Change in Mean VAS at Pre-injection and 30 Minutes Post Injection |
| NCT00428584 (10) [back to overview] | Secondary Outcome - Extension Phase: Diameter in Injection Site Redness |
| NCT00428584 (10) [back to overview] | Visual Analog Scale (VAS) of Patient Reported Pain: Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and 30 Minutes Post-injection Timepoints |
| NCT00428584 (10) [back to overview] | Secondary Outcome - Extension Phase: Number of Pain Free Patients at 30 Minutes Post Injection |
| NCT00436046 (8) [back to overview] | Local and/or Systemic Solicited Symptoms After Intranasal Immunization. |
| NCT00436046 (8) [back to overview] | Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza A/H1N1 and A/H3N2 at 14 Days After Intranasal Immunization. |
| NCT00436046 (8) [back to overview] | Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza A/H1N1 and A/H3N2 at 28 Days After Intranasal Immunization. |
| NCT00436046 (8) [back to overview] | Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza B at 28 Days After Intranasal Immunization. |
| NCT00436046 (8) [back to overview] | Unsolicited Adverse Events After Intranasal Immunization |
| NCT00436046 (8) [back to overview] | Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza B at 14 Days After Intranasal Immunization. |
| NCT00436046 (8) [back to overview] | Antibody Responses in Nasal Secretions to Influenza A/H1N1 and A/H3N2 at 28 Days After Intranasal Immunization |
| NCT00436046 (8) [back to overview] | Antibody Responses in Nasal Secretions to Influenza A/H1N1 and A/H3N2 at 14 Days After Intranasal Immunization. |
| NCT00436826 (42) [back to overview] | Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity |
| NCT00436826 (42) [back to overview] | Open Label Extension Period: Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Change From Baseline in Vital Signs- Weight |
| NCT00436826 (42) [back to overview] | Open Label Extension Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Change in New T1 Gd+ Lesions From Baseline to Week 96 |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Change in T1 Hypointense Lesion Volume From Baseline to Week 96 |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Change in T2 Lesion Volume From Baseline to Week 96 |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Changes From Baseline in Hemoglobin Level to Week 96 |
| NCT00436826 (42) [back to overview] | OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity |
| NCT00436826 (42) [back to overview] | Double Blind Period: Percent Change in Normalized Brain Volume From Baseline to Week 96 |
| NCT00436826 (42) [back to overview] | Double Blind Period: Percentage of Participants Qualifying Relapse-free |
| NCT00436826 (42) [back to overview] | Double Blind Period: Percentage of Participants With no Active T1 Gd-Enhanced Lesions at Week 96 |
| NCT00436826 (42) [back to overview] | Double Blind Period: Percentage of Participants With no Active T2 Lesions at Week 96 |
| NCT00436826 (42) [back to overview] | Double Blind Period: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) in Infections and Infestations System Organ Class (SOC) |
| NCT00436826 (42) [back to overview] | OLE and Safety Follow-up Period: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) in Infections and Infestations System Organ Class (SOC) |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Number of T1 Hypointense Lesions Per Participant Per Scan at Week 96 |
| NCT00436826 (42) [back to overview] | Open Label Extension Period: Mean Change From Baseline in Vital Signs- Pulse Rate |
| NCT00436826 (42) [back to overview] | OLE and Safety Follow-up Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs |
| NCT00436826 (42) [back to overview] | Double Blind Period: Time to Recovery From Grade 3 or 4 Hematological Toxicity |
| NCT00436826 (42) [back to overview] | Open Label Extension Period: Mean Change From Baseline in Vital Signs- Temperature |
| NCT00436826 (42) [back to overview] | Open Label Extension Period: Mean Change From Baseline in Vital Signs- Weight |
| NCT00436826 (42) [back to overview] | Double Blind Period and OLE Period: Time to 3-Month Sustained Expanded Disability Status Scale (EDSS) Progression |
| NCT00436826 (42) [back to overview] | Double Blind Period and OLE Period: Time to First Qualifying Relapse |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval |
| NCT00436826 (42) [back to overview] | Double Blind Period: Maximum Corrected QT Interval (QTc) |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Changes From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Week 96 |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Changes From Baseline in CD4+ Count, CD8+ Count, and CD19+ to Week 96 |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Changes in Lymphocytes, White Blood Cells (WBC), Neutrophils and Platelets Values From Baseline to Week 96 |
| NCT00436826 (42) [back to overview] | Double Blind Period: Number of Combined Unique Active (CUA) Lesions, Active Time Constant 2 (T2) Lesions, and Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan |
| NCT00436826 (42) [back to overview] | Double Blind Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs |
| NCT00436826 (42) [back to overview] | Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity |
| NCT00436826 (42) [back to overview] | Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity |
| NCT00436826 (42) [back to overview] | Double Blind Period: Time to Recovery From Grade 3 or 4 Hematological Toxicity |
| NCT00436826 (42) [back to overview] | Open Label Extension Period: Maximum Corrected QT Interval (Qtc) |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Change From Baseline in Vital Signs- Temperature |
| NCT00436826 (42) [back to overview] | Open Label Extension Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- Heart Rate |
| NCT00436826 (42) [back to overview] | Double Blind Period: Annualized Qualifying Relapse Rate |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- Heart Rate |
| NCT00436826 (42) [back to overview] | Double Blind Period: Mean Change From Baseline in Vital Signs- Pulse Rate |
| NCT00436826 (42) [back to overview] | Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity |
| NCT00436826 (42) [back to overview] | Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity |
| NCT00454181 (6) [back to overview] | Investigator Assessment Regarding Global Oral Changes. |
| NCT00454181 (6) [back to overview] | Total Surface Area of the Lips Covered by Warts |
| NCT00454181 (6) [back to overview] | Subject Questionnaire Regarding Global Oral Changes |
| NCT00454181 (6) [back to overview] | Investigator Assessment Regarding Changes in Warts |
| NCT00454181 (6) [back to overview] | Change in Total Oral Mucosal Area Covered by Warts. |
| NCT00454181 (6) [back to overview] | Subject Questionnaire Regarding Changes in Warts |
| NCT00459667 (5) [back to overview] | Liver Enzyme Elevations |
| NCT00459667 (5) [back to overview] | Percentage of Patients With Neutralizing Antibody Titer to IFNB-1b of Different Cut-off Values |
| NCT00459667 (5) [back to overview] | Flu-like-syndrome |
| NCT00459667 (5) [back to overview] | Injection-site Reactions |
| NCT00459667 (5) [back to overview] | Hematological Abnormalities |
| NCT00467077 (4) [back to overview] | Number of Participants With Overall Response as Measured by RECIST Criteria |
| NCT00467077 (4) [back to overview] | Overall Survival |
| NCT00467077 (4) [back to overview] | Progression-Free Survival |
| NCT00467077 (4) [back to overview] | Six-month Progression-free Survival |
| NCT00470093 (2) [back to overview] | Toxicity as Measured by Number of Participants Who Discontinued Treatment Due to Adverse Events |
| NCT00470093 (2) [back to overview] | Response Rate as Assessed by Number of Participants With Partial or Complete Response by Bladé Criteria. |
| NCT00483938 (3) [back to overview] | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) |
| NCT00483938 (3) [back to overview] | Percentage of Participants With Sustained Virological Response (SVR) (Groups A and B) |
| NCT00483938 (3) [back to overview] | Percentage of Participants With SVR (Groups C, D, E, and F) |
| NCT00489489 (8) [back to overview] | Annualized Relapse Rate [ARR]: Poisson Regression Estimates |
| NCT00489489 (8) [back to overview] | Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) |
| NCT00489489 (8) [back to overview] | Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) |
| NCT00489489 (8) [back to overview] | Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan |
| NCT00489489 (8) [back to overview] | Pharmacokinetic [PK]: Teriflunomide Plasma Concentration |
| NCT00489489 (8) [back to overview] | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) |
| NCT00489489 (8) [back to overview] | Overview of Adverse Events [AE] |
| NCT00489489 (8) [back to overview] | Overview of AE With Potential Risk of Occurrence |
| NCT00491179 (2) [back to overview] | Number of Participants With Histologic Response(HR) |
| NCT00491179 (2) [back to overview] | 1.Number of Participants With Sustained Virologic Response (SVR) 2.Number of Participants Who Droppoed Out of the Study Prematurely Due to Adverse Events (AEs) |
| NCT00491244 (2) [back to overview] | Sustained Virologic Response (SVR)Rate |
| NCT00491244 (2) [back to overview] | Adverse Event (AE)-Related Withdrawal Rate |
| NCT00493805 (2) [back to overview] | Sustained Virological Response (PCR 24 Weeks After End of Treatment) |
| NCT00493805 (2) [back to overview] | Early Virological Response in Participants With and Without Insulin Resistance |
| NCT00495131 (4) [back to overview] | Sustained Biochemical Response |
| NCT00495131 (4) [back to overview] | Sustained Virologic Response |
| NCT00495131 (4) [back to overview] | Treatment-related Withdrawal Rate |
| NCT00495131 (4) [back to overview] | Histologic Response |
| NCT00501644 (1) [back to overview] | Number of Patients With Response |
| NCT00501943 (6) [back to overview] | MRI Parameter- Percent Brain Volume Change for 2 Years |
| NCT00501943 (6) [back to overview] | Changes in Symbol Digit Modality Test (SDMT) |
| NCT00501943 (6) [back to overview] | Changes in Normalized Grey Matter Volume |
| NCT00501943 (6) [back to overview] | Changes in MS Functional Composite (MSFC) |
| NCT00501943 (6) [back to overview] | Changes in Normalized White Matter Volumes (nWMV) |
| NCT00501943 (6) [back to overview] | Changes in Peripapillary Retinal Nerve Fiber Layer Thickness (RNFL) |
| NCT00505635 (1) [back to overview] | Time to Progression (TTP) |
| NCT00520403 (4) [back to overview] | PFS - Time to Event |
| NCT00520403 (4) [back to overview] | Percentage of Participants With Disease Progression or Death |
| NCT00520403 (4) [back to overview] | Percentage of Participants With Objective Response (OR) |
| NCT00520403 (4) [back to overview] | Overall Survival (OS) |
| NCT00530348 (6) [back to overview] | Annualized Relapse Rate |
| NCT00530348 (6) [back to overview] | Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2 |
| NCT00530348 (6) [back to overview] | Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2 |
| NCT00530348 (6) [back to overview] | Percentage of Participants Who Were Relapse Free at Year 2 |
| NCT00530348 (6) [back to overview] | Percentage of Participants With Sustained Accumulation of Disability (SAD) |
| NCT00530348 (6) [back to overview] | Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2 |
| NCT00535847 (6) [back to overview] | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT00535847 (6) [back to overview] | Percentage of Subjects With End of Treatment Response |
| NCT00535847 (6) [back to overview] | Percentage of Subjects With Undetectable HCV RNA at Week 48 After Completion of Treatment Among Subjects Who Completed Assigned Treatment |
| NCT00535847 (6) [back to overview] | Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Treatment |
| NCT00535847 (6) [back to overview] | Percentage of Prior Relapsers With Undetectable HCV RNA |
| NCT00535847 (6) [back to overview] | Cross Tabulation of Extended Rapid Viral Response (eRVR) and Sustained Viral Response (SVR) in With Prior Response |
| NCT00536263 (11) [back to overview] | Number of Participants With Biochemical Response |
| NCT00536263 (11) [back to overview] | Number of Participants With Combined Response |
| NCT00536263 (11) [back to overview] | Number of Participants With HBV-DNA < 200 IU/mL |
| NCT00536263 (11) [back to overview] | Number of Participants With HBV-DNA Undetectable |
| NCT00536263 (11) [back to overview] | Number of Participants With HBeAg Loss |
| NCT00536263 (11) [back to overview] | Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss |
| NCT00536263 (11) [back to overview] | Change From Baseline in Liver Biopsy Score |
| NCT00536263 (11) [back to overview] | HBe Seroconversion |
| NCT00536263 (11) [back to overview] | Hepatitis B Surface Antigen (HBs) Seroconversion |
| NCT00536263 (11) [back to overview] | Hepatitis B Surface Antigen (HBsAg) Loss |
| NCT00536263 (11) [back to overview] | Number of Participants With Hepatitis B Virus - Deoxyriboncleic Acid (HBV-DNA) <20,000 IU/mL |
| NCT00539591 (23) [back to overview] | Volume of Central Compartment (Vc) of Pegylated Interferon ɑ-2B |
| NCT00539591 (23) [back to overview] | Mean Total PedsQL 4.0 Scores for Child Quality of Life (QoL) Assessments (Stratum B) |
| NCT00539591 (23) [back to overview] | Mean Total PedsQL 4.0 Scores for Parent Quality of Life Assessments (Stratum A) |
| NCT00539591 (23) [back to overview] | Median Steady State Trough Concentration of Pegylated Interferon ɑ-2B |
| NCT00539591 (23) [back to overview] | Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Strata B1 and B2 |
| NCT00539591 (23) [back to overview] | Probability of Event-free Survival (EFS) of Stratum A Participants |
| NCT00539591 (23) [back to overview] | Mean Total PedsQL 3.0 Scores for Parent Cancer Quality of Life (QoL) Assessments (Stratum A) |
| NCT00539591 (23) [back to overview] | Systemic Clearance (CL) of Interferon ɑ-2B |
| NCT00539591 (23) [back to overview] | Apparent Clearance (CL) of Pegylated Interferon ɑ-2B |
| NCT00539591 (23) [back to overview] | Area Under the Curve (AUC) of Interferon ɑ-2b |
| NCT00539591 (23) [back to overview] | Area Under the Curve (AUC) of Pegylated Interferon ɑ-2B |
| NCT00539591 (23) [back to overview] | ɑ Half Life of Pegylated Interferon ɑ-2B |
| NCT00539591 (23) [back to overview] | BASC-2 Psychological Assessment (Stratum A) |
| NCT00539591 (23) [back to overview] | BRIEF Psychological Assessment (Stratum A) |
| NCT00539591 (23) [back to overview] | Mean Total PedsQL 3.0 Scores for Child Cancer Quality of Life (QoL) Assessments (Stratum A) |
| NCT00539591 (23) [back to overview] | Mean Total PedsQL 3.0 Scores for Child Cancer Quality of Life (QoL) Assessments (Stratum B) |
| NCT00539591 (23) [back to overview] | Volume of Central Compartment (Vc) of Interferon ɑ-2b |
| NCT00539591 (23) [back to overview] | Mean Total PedsQL 3.0 Scores for Parent Cancer Quality of Life (QoL) Assessments (Stratum B) |
| NCT00539591 (23) [back to overview] | Mean Total PedsQL 4.0 Scores for Child Quality of Life (QoL) Assessments (Stratum A) |
| NCT00539591 (23) [back to overview] | Mean Total PedsQL 4.0 Scores for Parent Quality of Life Assessments (Stratum B) |
| NCT00539591 (23) [back to overview] | Half-Life of Interferon ɑ-2b |
| NCT00539591 (23) [back to overview] | Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Stratum A Patients |
| NCT00539591 (23) [back to overview] | Tumor Response Rate |
| NCT00548405 (6) [back to overview] | Annualized Relapse Rate |
| NCT00548405 (6) [back to overview] | Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2 |
| NCT00548405 (6) [back to overview] | Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2 |
| NCT00548405 (6) [back to overview] | Percentage of Participants Who Were Relapse Free at Year 2 |
| NCT00548405 (6) [back to overview] | Percentage of Participants With Sustained Accumulation of Disability (SAD) |
| NCT00548405 (6) [back to overview] | Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2 |
| NCT00548847 (2) [back to overview] | Overall Survival at 6 Months (Evaluate Overall Responses; Perform Lab Experiments to Test Hypothesis That Exposure to Interferon-alpha and GM-CSF Up-regulates Co-stimulatory Molecule Expression on Relapsed Acute Leukemia Cells) |
| NCT00548847 (2) [back to overview] | Efficacy of GM-CSF and Pegylated Interferon-alpha 2b When Administered to Patients With AML, ALL, Blast Phase CML, and MDS Relapse After Allogeneic Transplantation, Defined as Progression-free Survival of > 33% at 3 Months |
| NCT00569127 (6) [back to overview] | Central Review-based Progression-Free Survival |
| NCT00569127 (6) [back to overview] | Objective Response (Confirmed and Unconfirmed Complete Response and Partial Response) |
| NCT00569127 (6) [back to overview] | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug |
| NCT00569127 (6) [back to overview] | Overall Survival |
| NCT00569127 (6) [back to overview] | Local Progression-Free Survival (Investigator Assessed) |
| NCT00569127 (6) [back to overview] | Time to Treatment Failure |
| NCT00577993 (2) [back to overview] | Number of Participants With Overall Survival (10 Years) by Treatment |
| NCT00577993 (2) [back to overview] | Number of Participants With Progression Free Survival (10 Years) by Treatment |
| NCT00580801 (12) [back to overview] | Percentage of Participants With Sustained Viral Response (SVR) |
| NCT00580801 (12) [back to overview] | Percentage of Participants With Viral Response (Undetectable HCV RNA) |
| NCT00580801 (12) [back to overview] | Time to Reach the Maximum Serum Concentration (Tmax) of Telaprevir |
| NCT00580801 (12) [back to overview] | Area Under the Serum Concentration-Time Curve (AUC) |
| NCT00580801 (12) [back to overview] | Number of Participants With Viral Breakthrough (Detectable HCV RNA) |
| NCT00580801 (12) [back to overview] | Average Steady-State Serum Concentration (Css,av) of Telaprevir |
| NCT00580801 (12) [back to overview] | Median Time to First Viral Response (Undetectable HCV RNA) |
| NCT00580801 (12) [back to overview] | Minimum Serum Concentration (Cmin) of Telaprevir on Day 15 |
| NCT00580801 (12) [back to overview] | Percentage of Participants With Relapse |
| NCT00580801 (12) [back to overview] | Pre-Dose Serum Concentration (C[0h]) of Telaprevir |
| NCT00580801 (12) [back to overview] | Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Day 15 |
| NCT00580801 (12) [back to overview] | Maximum Serum Concentration (Cmax) of Telaprevir |
| NCT00594880 (3) [back to overview] | HIV Viral Load < 400 Copies/ml |
| NCT00594880 (3) [back to overview] | HIV Viral Load < 48 Copies/ml |
| NCT00594880 (3) [back to overview] | HIV Viral Load < 400 Copies/ml |
| NCT00605215 (8) [back to overview] | Change From Baseline in General Health Status as Assessed by the Short-Form General Health Survey (SF-36) Patient-Reported Questionnaire For Mental Component Summary (MCS) Scores |
| NCT00605215 (8) [back to overview] | Change From Baseline in General Health Status as Assessed by the Short-Form General Health Survey (SF-36) Patient-Reported Questionnaire For Physical Component Summary (PCS) Scores |
| NCT00605215 (8) [back to overview] | Percent Change From Baseline in Brain Volume |
| NCT00605215 (8) [back to overview] | Accumulation of Physical Disability Measured by the Number of Participants With Confirmed Progression of EDSS |
| NCT00605215 (8) [back to overview] | Change From Baseline in Disability as Assessed by the Multiple Sclerosis Functional Composite (MSFC) Score |
| NCT00605215 (8) [back to overview] | Annualized Rate of Confirmed Relapses |
| NCT00605215 (8) [back to overview] | Cumulative Number of Enhancing Lesions on T1-Weighted Images |
| NCT00605215 (8) [back to overview] | Cumulative Number of New or Enlarging Hypointense Lesions on Enhanced T1 Scans |
| NCT00606086 (1) [back to overview] | EVR (Early Virologic Response) |
| NCT00613509 (9) [back to overview] | Summary of Disease Progression in Study Participants, Intent-to-treat Population |
| NCT00613509 (9) [back to overview] | Summary of Cellular Immune Response to the Vaccination or Treatment (Percent Regulatory T-Cells Responses) |
| NCT00613509 (9) [back to overview] | Number of Participants With a Vaccine-Induced Increase of CD8 T-Cell Positive Response by Antigen |
| NCT00613509 (9) [back to overview] | Number of Participants With a Vaccine-Induced Increase of CD4 T-Cell Positive Response by Antigen |
| NCT00613509 (9) [back to overview] | Number of Participants Reporting a Grade 3 or Grade 4 Adverse Events by Preferred Term |
| NCT00613509 (9) [back to overview] | Best Overall Objective Response as Number of Participants Responding in the Intent-to-treat Population |
| NCT00613509 (9) [back to overview] | Progression-Free Survival Time by Response Evaluation Criteria in Solid Tumor (RECIST) Criteria in the Intent-to-treat Population |
| NCT00613509 (9) [back to overview] | Best Overall Objective Response as Mean Duration of Response (Weeks) in the Intent-to-treat Population |
| NCT00613509 (9) [back to overview] | Best Overall Objective Response in the Intent-to-treat Population |
| NCT00616434 (3) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT00616434 (3) [back to overview] | Percentage of Participants With a Clinical Response |
| NCT00616434 (3) [back to overview] | Percentage of Participants With a Decrease on Simple Clinical Colitis Activity Index (SCCAI) of ≥3 Points at Week 8 |
| NCT00627926 (13) [back to overview] | Number of Subjects With Undetectable HCV RNA at Week 72 |
| NCT00627926 (13) [back to overview] | Number of Subjects Achieving Extended Rapid Viral Response (eRVR), Demonstrated by Achieving Undetectable HCV RNA at Week 4 and at Week 12 |
| NCT00627926 (13) [back to overview] | Number of Subjects Achieving Rapid Viral Response (RVR), Demonstrated by Achieving Undetectable HCV RNA 4 Weeks After Starting Study Treatment |
| NCT00627926 (13) [back to overview] | Number of Subjects With Undetectable HCV RNA 12 Weeks After Last Planned Dose of Study Treatment |
| NCT00627926 (13) [back to overview] | Number of Subjects With Undetectable HCV RNA 24 Weeks After Last Actual Dose of Study Treatment |
| NCT00627926 (13) [back to overview] | Number of Subjects With Undetectable HCV RNA at End of Treatment (EOT) |
| NCT00627926 (13) [back to overview] | Number of Subjects With Undetectable HCV RNA at Week 12 |
| NCT00627926 (13) [back to overview] | Biochemical Response: Number of Subjects With Grade 3 and 4 Shifts From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels |
| NCT00627926 (13) [back to overview] | Fatigue Severity Scale (FSS) Total Score |
| NCT00627926 (13) [back to overview] | Noninvasive Markers of Fibrosis: Number of Subjects With Improvement in FibroTest Analysis |
| NCT00627926 (13) [back to overview] | Number of Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels 24 Weeks After Last Planned Dose of Study Treatment |
| NCT00627926 (13) [back to overview] | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT00627926 (13) [back to overview] | Number of Subjects With Viral Relapse Planned and Viral Relapse Actual |
| NCT00631371 (4) [back to overview] | Progression-Free Survival (PFS): Investigator-Assessment |
| NCT00631371 (4) [back to overview] | Percentage of Participants With Objective Response (Complete Response/Partial Response): Independent-Assessment |
| NCT00631371 (4) [back to overview] | Progression-Free Survival (PFS): Independent-Assessment |
| NCT00631371 (4) [back to overview] | Overall Survival (OS) |
| NCT00676715 (6) [back to overview] | Change From Baseline in Total Volume of T2 Lesions on MRI Scans of the Brain at Week 24 |
| NCT00676715 (6) [back to overview] | Total Number of Gadolinium-Enhancing T1 Lesions at Weeks |
| NCT00676715 (6) [back to overview] | Total Number of Gadolinium-Enhancing T1 Lesions Observed on MRI Scans of the Brain |
| NCT00676715 (6) [back to overview] | Percentage of Participants Who Remained Relapse Free at Week 24 |
| NCT00676715 (6) [back to overview] | Annualized Protocol Defined Relapse Rate at Week 24 |
| NCT00676715 (6) [back to overview] | Total Number of New Gadolinium-Enhancing T1 Lesions Observed by MRI Scans of the Brain |
| NCT00679289 (3) [back to overview] | Number of Patients With Treatment-emergent Adverse Events (TEAEs) |
| NCT00679289 (3) [back to overview] | Median Progression-free Survival (PFS) With 95% Confidence Intervals |
| NCT00679289 (3) [back to overview] | Maximum KW2871 Antibody Levels in Plasma Following the First Infusion |
| NCT00686517 (5) [back to overview] | Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]). |
| NCT00686517 (5) [back to overview] | Virologic Response at the End of Treatment Follow-up (ETR) |
| NCT00686517 (5) [back to overview] | Number of Participants With Sustained Response (SR) at the End of the 6-month Follow-up Period |
| NCT00686517 (5) [back to overview] | Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization |
| NCT00686517 (5) [back to overview] | Number of Participants With Rapid Virologic Response (RVR) |
| NCT00686777 (3) [back to overview] | Percentage of Participants With Sustained Virologic Response (SVR) at 24 Weeks After the End of Treatment (EOT) or Discontinuation |
| NCT00686777 (3) [back to overview] | Percentage of Participants With HCV-RNA Negativity at 24 Weeks of Treatment and at EOT |
| NCT00686777 (3) [back to overview] | Number of Participants Discontinuing Treatment |
| NCT00686881 (3) [back to overview] | Number of Participants With Change in Metavir Inflammation Score |
| NCT00686881 (3) [back to overview] | Number of Participants With Alanine Aminotransferase (ALT) Normalization of >16 Weeks Duration |
| NCT00686881 (3) [back to overview] | Number of Participants With Change in Metavir Fibrosis Score |
| NCT00695019 (8) [back to overview] | Change in Serum ALT |
| NCT00695019 (8) [back to overview] | Sustained Virologic Response Rate |
| NCT00695019 (8) [back to overview] | Relapse Rate |
| NCT00695019 (8) [back to overview] | Normalization of Platelets |
| NCT00695019 (8) [back to overview] | Normalization of ALT |
| NCT00695019 (8) [back to overview] | Change in Social Functioning |
| NCT00695019 (8) [back to overview] | Change in Serum HCV RNA Concentration |
| NCT00695019 (8) [back to overview] | Change in Fibrotest Score |
| NCT00704184 (6) [back to overview] | Number of Participants With ≥2-log10 Decrease in HCV RNA |
| NCT00704184 (6) [back to overview] | Number of Participants With ≥3-log10 Decrease in HCV RNA |
| NCT00704184 (6) [back to overview] | Percentage of Participants Achieving RVR |
| NCT00704184 (6) [back to overview] | Mean Log Change From Baseline in HCV RNA |
| NCT00704184 (6) [back to overview] | Number of Participants Discontinuing From Study Therapy Due to AEs |
| NCT00704184 (6) [back to overview] | Number of Participants Experiencing an Adverse Event (AE) |
| NCT00704405 (6) [back to overview] | Percentage of Participants Achieving SVR24 After 24 Weeks of Vaniprevir 600 mg b.i.d. |
| NCT00704405 (6) [back to overview] | Percentage of Participants Achieving SVR24 Following Treatment With Vaniprevir 600 mg b.i.d. |
| NCT00704405 (6) [back to overview] | Percentage of Participants Achieving SVR24 Following Treatment With Vaniprevir 300 mg b.i.d. |
| NCT00704405 (6) [back to overview] | Percentage of Participants Achieving cEVR |
| NCT00704405 (6) [back to overview] | Number of Participants Experiencing an Adverse Event (AE) |
| NCT00704405 (6) [back to overview] | Number of Participants Discontinuing From Study Treatment Due to AEs |
| NCT00705224 (5) [back to overview] | Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline |
| NCT00705224 (5) [back to overview] | Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study |
| NCT00705224 (5) [back to overview] | Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline |
| NCT00705224 (5) [back to overview] | Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline |
| NCT00705224 (5) [back to overview] | Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline |
| NCT00708500 (4) [back to overview] | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. |
| NCT00708500 (4) [back to overview] | Number of Participants With Early Virologic Response. |
| NCT00708500 (4) [back to overview] | Sustained Virologic Response (SVR) Rate in the Full Analysis Set (FAS) Population. |
| NCT00708500 (4) [back to overview] | Sustained Virologic Response (SVR) Rate in the Modified Intent to Treat (mITT) Population. |
| NCT00719264 (8) [back to overview] | Response Duration Differences in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab |
| NCT00719264 (8) [back to overview] | Time to Definitive Deterioration of the Functional Assessment of Cancer Therapy Kidney Symptom Index, Disease Related Symptoms (FKSI-DRS) Risk Score by at Least 2 Score Units |
| NCT00719264 (8) [back to overview] | Duration of Exposure of RAD001 in Participants Randomized to the Treatment Combination of RAD001 and Bevacizumab |
| NCT00719264 (8) [back to overview] | Overall Survival (OS) Treatment Effect in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab |
| NCT00719264 (8) [back to overview] | Progression-free Survival (PFS) of Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab |
| NCT00719264 (8) [back to overview] | Time to Definitive Deterioration of the Global Health Status and the Physical Functioning (PF) Subscale Scores of the European Organization for the Research and Treatment of Cancer (EORTC)-Core Quality of Life Questionnaire (QLQ-C30) by at Least 10% |
| NCT00719264 (8) [back to overview] | Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events and Deaths |
| NCT00719264 (8) [back to overview] | Best Overall Response in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab |
| NCT00723710 (1) [back to overview] | Number of Participants Who Completed Treatment |
| NCT00724061 (1) [back to overview] | Number of Dose Limiting Toxicities (DLTs) Observed During Dose Escalation of PEG-IFN-α-2b |
| NCT00724464 (8) [back to overview] | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline |
| NCT00724464 (8) [back to overview] | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up |
| NCT00724464 (8) [back to overview] | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Alanine Aminotransferase (ALT) Levels at Baseline |
| NCT00724464 (8) [back to overview] | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Study Treatment Dosage Modification |
| NCT00724464 (8) [back to overview] | Number of Participants Who Demonstrated Virological Relapse as Assessed at 24-week Post-treatment Follow-up |
| NCT00724464 (8) [back to overview] | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV-RNA Viral Load at Baseline |
| NCT00724464 (8) [back to overview] | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Achievement of Rapid Virological Response |
| NCT00724464 (8) [back to overview] | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline |
| NCT00724893 (49) [back to overview] | Number of Participants With EOT Response by Chronic HCV Genotype (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Chronic HCV Genotype (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Chronic HCV Genotype + Viral Load (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving RVR by Liver Fibrosis Stage (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving RVR by Gender (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR, Excluding Participants Who Discontinued Prior to EVR Evaluation (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving RVR by Chronic HCV Genotype 1 Subtype (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving EVR by Weight (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving EVR by Race (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving EVR by Liver Fibrosis Stage (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving EVR by Gender (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving EVR by Chronic HCV Genotype 1 Subtype (Stage 2) |
| NCT00724893 (49) [back to overview] | The Number of Participants Achieving Viral Response at 12 Weeks After EOT, Excluding Participants Who Discontinued Prior to EVR Evaluation and Participants With Missing Data (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Weight (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Weight (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Chronic HCV Genotype 1 Subtype (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by EVR Type (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Gender (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Gender (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Human Immunodeficiency Virus (HIV) Status (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Liver Fibrosis Score (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Liver Fibrosis Stage (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Race (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Race (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Viral Load (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving Viral Response at Any Evaluation Point (Stage 1) |
| NCT00724893 (49) [back to overview] | Percentage of Compliance for Participants Achieving SVR Based on Medication Adherence Questionnaire (MAQ) (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving Sustained Viral Response (SVR) (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving RVR Who Achieved SVR (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving Rapid Virologic Response (RVR) (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving EVR (Stage 2) |
| NCT00724893 (49) [back to overview] | Relapse Rate by HCV Genotype (Stage 1) |
| NCT00724893 (49) [back to overview] | The Number of Participants Achieving Viral Response at 12 Weeks After EOT by Chronic HCV Genotype (Stage 1) |
| NCT00724893 (49) [back to overview] | The Number of Participants Achieving Viral Response at 12 Weeks After EOT by Liver Fibrosis Stage (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving EVR (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving EVR Who Achieved SVR (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving RVR by Weight (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving RVR by Race (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving Viral Response at 12 Weeks After EOT, Excluding Participants Who Discontinued Prior to EVR Evaluation (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving Viral Response at 12 Weeks After EOT (Stage 1) |
| NCT00724893 (49) [back to overview] | The Number of Participants Achieving SVR Excluding Participants Who Discontinued Prior to EVR Evaluation and Participants With Missing Data (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants With End of Treatment (EOT) Response (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Discontinued From Study Treatment Due to Adverse Events (Stage 1 and Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving Viral Response at Any Evaluation Point, Excluding Participants Who Discontinued Treatment Prior to Early Virologic Response (EVR) Evaluation (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Discontinued From Study Drug Due to Adverse Events by Chronic HCV Genotype (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Weight + Chronic HCV Genotype (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR by Chronic HCV Genotype + Liver Fibrosis Stage (Stage 1) |
| NCT00724893 (49) [back to overview] | Number of Participants Achieving SVR (Stage 2) |
| NCT00724893 (49) [back to overview] | Number of Participants With EVR by Selected Chronic HCV Genotypes (Stage 1) |
| NCT00725751 (3) [back to overview] | Number of Participants Who Received Antiviral Treatment Who Were Also on Substitution Therapy |
| NCT00725751 (3) [back to overview] | Number of Participants Who Completed Treatment With PegIFN-2b/Ribavirin |
| NCT00725751 (3) [back to overview] | Number of Participants Who Achieved Sustained Virologic Response (SVR) |
| NCT00726557 (2) [back to overview] | Number of Participants Who Tolerated Treatment With PegIntron 1.5 mcg/kg/Week + Rebetol 10.6 mg/kg/Week |
| NCT00726557 (2) [back to overview] | Number of Drug-substituted Participants Who Achieved Sustained Virological Response (SVR) With PegIntron 1.5 μg/kg/Week and Rebetol (10.6 mg/kg/Day) in Substitution Centers Under Routine Conditions |
| NCT00738530 (10) [back to overview] | Time to Progression (TTP) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) |
| NCT00738530 (10) [back to overview] | Time to Treatment Failure (TTF) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) |
| NCT00738530 (10) [back to overview] | Change From Baseline in Karnofsky Performance Status |
| NCT00738530 (10) [back to overview] | Percentage of Participants With Best Overall Response According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) |
| NCT00738530 (10) [back to overview] | Overall Survival (OS) Duration |
| NCT00738530 (10) [back to overview] | Percentage of Participants Who Died |
| NCT00738530 (10) [back to overview] | Percentage of Participants With Disease Progression or Death |
| NCT00738530 (10) [back to overview] | Percentage of Participants With Objective Response According to mRECIST |
| NCT00738530 (10) [back to overview] | Percentage of Participants With Treatment Failure |
| NCT00738530 (10) [back to overview] | Progression Free Survival (PFS) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) |
| NCT00749684 (2) [back to overview] | Number of Participants With Disease Recurrence |
| NCT00749684 (2) [back to overview] | Relapse Free Survival Time |
| NCT00784836 (1) [back to overview] | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT00786643 (3) [back to overview] | Time to Progression |
| NCT00786643 (3) [back to overview] | Best Response (BR) |
| NCT00786643 (3) [back to overview] | Early Response Rate (RR) (Stratum 1 Only) |
| NCT00789685 (3) [back to overview] | All Cause Mortality Rate at 6 Months |
| NCT00789685 (3) [back to overview] | Clinically Significant Treatment Emergent Events |
| NCT00789685 (3) [back to overview] | All Cause Mortality at Day 28 |
| NCT00796757 (9) [back to overview] | OS - Percentage of Participants With an Event |
| NCT00796757 (9) [back to overview] | Percentage of Participants With a Best Overall Response of Complete Reponse (CR) or Partial Response (PR) |
| NCT00796757 (9) [back to overview] | OS - Time to Event |
| NCT00796757 (9) [back to overview] | EQ-5D - Visual Analog Scale (VAS) |
| NCT00796757 (9) [back to overview] | Progression-Free Survival (PFS) - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months |
| NCT00796757 (9) [back to overview] | Percentage of Participants With Any Health Problems as Assessed by the European Quality of Life 5 Dimensions (EQ-5D) by Visit |
| NCT00796757 (9) [back to overview] | Overall Survival (OS) - Percentage of Participants Estimated to be Alive at 12 and 24 Months |
| NCT00796757 (9) [back to overview] | PFS - Time to Event |
| NCT00796757 (9) [back to overview] | PFS - Percentage of Participants With an Event |
| NCT00800735 (1) [back to overview] | Percentage of Participants Who Experienced at Least 1 Adverse Event. |
| NCT00811395 (9) [back to overview] | Cerebral MRI Assessment: Total Volume of Gd-enhancing T1-lesions Per Scan |
| NCT00811395 (9) [back to overview] | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA] |
| NCT00811395 (9) [back to overview] | Overview of 12-week Sustained Disability Progression |
| NCT00811395 (9) [back to overview] | Overview of Adverse Events [AE] |
| NCT00811395 (9) [back to overview] | Overview of AE With Potential Risk of Occurence |
| NCT00811395 (9) [back to overview] | Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints |
| NCT00811395 (9) [back to overview] | Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) |
| NCT00811395 (9) [back to overview] | Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) |
| NCT00811395 (9) [back to overview] | Annualized Relapse Rate [ARR]: Poisson Regression Estimates |
| NCT00828204 (9) [back to overview] | Percentage of Participants Who Indicated No Difficulty With the Injection Procedure of the Manual Injection or the Avonex Single-use Autoinjector |
| NCT00828204 (9) [back to overview] | Percentage of Participants Who Rated the Avonex Single-use Autoinjector Printed and DVD Training Materials as Very Effective |
| NCT00828204 (9) [back to overview] | Mean Score for Ease of Use Grading Scale |
| NCT00828204 (9) [back to overview] | Mean Pain Score After Injection |
| NCT00828204 (9) [back to overview] | Percentage of Participants Who Indicated a Preference for the Avonex Single-use Autoinjector Over the Manual Avonex Prefilled Syringe |
| NCT00828204 (9) [back to overview] | Percentage of Participants in the Main Subset With Overall Success Using the Avonex Single-Use Autoinjector |
| NCT00828204 (9) [back to overview] | Number of Participants in the Initial Subset Who Were Satisfied With the Avonex Single-Use Autoinjector |
| NCT00828204 (9) [back to overview] | Mean Score for Initial Subset on Autoinjector Instructions Grading Scale |
| NCT00828204 (9) [back to overview] | Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector |
| NCT00845676 (1) [back to overview] | Sustained Virologic Response (SVR) |
| NCT00846430 (4) [back to overview] | At Least 50% Shrinkage in Tumor Measurements by Physical Examination |
| NCT00846430 (4) [back to overview] | No Reported Psychological Toxicity Based Upon Psychological Evaluations |
| NCT00846430 (4) [back to overview] | Response by MRI Measurements |
| NCT00846430 (4) [back to overview] | Improvement of Symptoms and Pain |
| NCT00851890 (14) [back to overview] | Percentage of Participants With at Least a 2 log10 Maximal Decrease in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Treatment |
| NCT00851890 (14) [back to overview] | Number of Participants Having Treatment-emergent Adverse Events (AEs) |
| NCT00851890 (14) [back to overview] | Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Monotherapy Treatment |
| NCT00851890 (14) [back to overview] | Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28 |
| NCT00851890 (14) [back to overview] | Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC12) of ABT-333 |
| NCT00851890 (14) [back to overview] | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 25 IU/mL (the Lower Limit of Quantitation [LLOQ]) at Day 28 or Final Visit |
| NCT00851890 (14) [back to overview] | Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28 or Final Visit |
| NCT00851890 (14) [back to overview] | Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28 |
| NCT00851890 (14) [back to overview] | Serum Concentrations of Pegylated Interferon (pegIFN) |
| NCT00851890 (14) [back to overview] | Time to Maximum Plasma Concentration (Tmax) of ABT-333 |
| NCT00851890 (14) [back to overview] | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 10 IU/mL (Lower Limit of Detection [LLOD]) at Day 28 or Final Visit |
| NCT00851890 (14) [back to overview] | Plasma Concentrations of Ribavirin (RBV) |
| NCT00851890 (14) [back to overview] | Maximum Plasma Concentration (Cmax) of ABT-333 |
| NCT00851890 (14) [back to overview] | Number of Participants With Maximal Phenotypic Resistance to ABT-333 >10 Fold Relative to Baseline Through Day 28 |
| NCT00854581 (7) [back to overview] | Failure-free Survival (FFS) |
| NCT00854581 (7) [back to overview] | Expressions of c-Rel, IRF-4 and Other Molecular Events in Participants |
| NCT00854581 (7) [back to overview] | The Effect of Valproic Acid Therapy on Persistence of Clonal Disease in Patients Who Achieve Clinical Remission |
| NCT00854581 (7) [back to overview] | Presence of Minimal Residual Disease at 3 and 6 Months of Maintained Remission and at 1 Year Post Initiation of Therapy |
| NCT00854581 (7) [back to overview] | Number of Patients Achieving Clinical Response to Protocol Therapy Who Lack IRF-4 and/or c-Rel Expression. |
| NCT00854581 (7) [back to overview] | Number of Participants Exhibiting NF-kB Inhibition Upon Treatment With AZT in Vivo |
| NCT00854581 (7) [back to overview] | Overall Survival |
| NCT00880763 (6) [back to overview] | Number of Participants Who Discontinued Study Drug Due to an Adverse Event |
| NCT00880763 (6) [back to overview] | Number of Participants Who Experienced at Least One Adverse Event |
| NCT00880763 (6) [back to overview] | Percentage of Participants Achieving a > or = 3-log10 Decrease in HCV RNA From Baseline to Week 4 |
| NCT00880763 (6) [back to overview] | Percentage of Participants Achieving a > or = 2-log10 Decrease in HCV RNA From Baseline to Week 4 |
| NCT00880763 (6) [back to overview] | Percentage of Participants Achieving Rapid Viral Response |
| NCT00880763 (6) [back to overview] | Change From Baseline in HCV RNA in log10 at Week 4 |
| NCT00883337 (8) [back to overview] | Core Treatment Period: Overview of Failures |
| NCT00883337 (8) [back to overview] | Core Treatment Period: Overview of Adverse Events [AE] |
| NCT00883337 (8) [back to overview] | Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score |
| NCT00883337 (8) [back to overview] | Core Treatment Period: Annualized Relapse Rate [ARR] - Poisson Regression Estimates |
| NCT00883337 (8) [back to overview] | Extension Treatment Period: Overview of AEs |
| NCT00883337 (8) [back to overview] | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores |
| NCT00883337 (8) [back to overview] | Extension Treatment Period: ARR Poisson Regression Estimates |
| NCT00883337 (8) [back to overview] | Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints |
| NCT00895947 (6) [back to overview] | Incidence/Severity of Viral Respiratory Infections |
| NCT00895947 (6) [back to overview] | Negative Events Related to Cold/Flu Symptoms |
| NCT00895947 (6) [back to overview] | Symptom Incidence/Severity |
| NCT00895947 (6) [back to overview] | Acute Respiratory Illness |
| NCT00895947 (6) [back to overview] | Frequency of Influenza-like Illness |
| NCT00895947 (6) [back to overview] | Impact of Cold/Flu Symptoms |
| NCT00906399 (4) [back to overview] | Number of New Or Newly Enlarging T2 Hyperintense Lesions at 1 Year |
| NCT00906399 (4) [back to overview] | Proportion of Participants Relapsed at 1 Year |
| NCT00906399 (4) [back to overview] | Estimated Proportion of Participants With Sustained Disability Progression at 1 Year |
| NCT00906399 (4) [back to overview] | Annualized Relapse Rate (ARR) at 1 Year |
| NCT00911443 (3) [back to overview] | Overall Survival |
| NCT00911443 (3) [back to overview] | Overall Tumor Response |
| NCT00911443 (3) [back to overview] | Progression Free Survival |
| NCT00919633 (3) [back to overview] | Early Virologic Response (EVR) |
| NCT00919633 (3) [back to overview] | Rapid Virologic Response (RVR) |
| NCT00919633 (3) [back to overview] | Viral Load: Incidence of Sustained Virologic Response (SVR) |
| NCT00943761 (4) [back to overview] | Number of Participants Who Experienced an Adverse Event |
| NCT00943761 (4) [back to overview] | Number of Participants Who Experienced a Serious Adverse Event |
| NCT00943761 (4) [back to overview] | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event |
| NCT00943761 (4) [back to overview] | Percentage of Participants Who Achieved Sustained Viral Response 24 Weeks After the End of Treatment (SVR24) |
| NCT00947349 (33) [back to overview] | t1/2,ss for BI 201335 ZW |
| NCT00947349 (33) [back to overview] | Tmax for BI 201335 ZW |
| NCT00947349 (33) [back to overview] | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV |
| NCT00947349 (33) [back to overview] | Tmax for RBV |
| NCT00947349 (33) [back to overview] | Tmax, ss for BI 201335 ZW |
| NCT00947349 (33) [back to overview] | Tmax, ss for RBV |
| NCT00947349 (33) [back to overview] | Week 2 Virological Response (W2VR) |
| NCT00947349 (33) [back to overview] | Week 4 Virological Response (W4VR) |
| NCT00947349 (33) [back to overview] | Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV |
| NCT00947349 (33) [back to overview] | Assessment of Tolerability in Triple Combination Therapy |
| NCT00947349 (33) [back to overview] | Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy |
| NCT00947349 (33) [back to overview] | CL/F,ss for BI 201335 ZW |
| NCT00947349 (33) [back to overview] | AUCτ,1 for BI 201335 ZW |
| NCT00947349 (33) [back to overview] | AUCτ,1 for Ribavirin (RBV) |
| NCT00947349 (33) [back to overview] | AUCτ,ss of BI 201335 ZW |
| NCT00947349 (33) [back to overview] | AUCτ,ss of RBV |
| NCT00947349 (33) [back to overview] | Cavg for BI 201335 ZW |
| NCT00947349 (33) [back to overview] | Cavg for RBV |
| NCT00947349 (33) [back to overview] | Change From Baseline in HCV Viral Load |
| NCT00947349 (33) [back to overview] | Cmax of BI 201335 ZW |
| NCT00947349 (33) [back to overview] | Cmax of RBV |
| NCT00947349 (33) [back to overview] | Cmax,ss of BI 201335 ZW |
| NCT00947349 (33) [back to overview] | Cmax,ss of RBV |
| NCT00947349 (33) [back to overview] | Cmin,ss for BI 201335 ZW |
| NCT00947349 (33) [back to overview] | Cmin,ss for RBV |
| NCT00947349 (33) [back to overview] | Complete Early Virological Response (cEVR) |
| NCT00947349 (33) [back to overview] | Day 28 Virologic Response |
| NCT00947349 (33) [back to overview] | Early Virological Response (EVR) |
| NCT00947349 (33) [back to overview] | End of Treatment Response (ETR) |
| NCT00947349 (33) [back to overview] | Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN α-2a and RBV |
| NCT00947349 (33) [back to overview] | Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy |
| NCT00947349 (33) [back to overview] | Rapid Virological Response (RVR) |
| NCT00947349 (33) [back to overview] | Sustained Virologic Response (SVR) |
| NCT00959699 (6) [back to overview] | Percentage of Participants With HCV Virologic Breakthrough or Incomplete Virologic Response/Rebound |
| NCT00959699 (6) [back to overview] | Change From Baseline in log10 HCV-RNA at Treatment Week 4 (TW4) |
| NCT00959699 (6) [back to overview] | Percentage of Participants Achieving SVR24 Among Randomized Participants Who Received At Least One Dose of Boceprevir (Experimental) or Placebo (Control) |
| NCT00959699 (6) [back to overview] | Percentage of Participants Achieving Sustained Viral Response (SVR) at Follow-up Week 24 (FW24) Among Randomized Participants Who Received At Least One Dose of Trial Medication |
| NCT00959699 (6) [back to overview] | Percentage of Participants With Early Virologic Response (EVR) Who Achieved SVR24 |
| NCT00959699 (6) [back to overview] | Percentage of Participants With Undetectable HCV-RNA at Follow-up Week 12 (FW12) |
| NCT00984620 (16) [back to overview] | Time to Reach a Plasma HCV RNA Level BLD While on Treatment |
| NCT00984620 (16) [back to overview] | Laboratory Test Abnormalities and Study Medication Tolerabilities |
| NCT00984620 (16) [back to overview] | Number of Participants With Clinically Relevant Abnormalities Vital Signs, and Physical Examination |
| NCT00984620 (16) [back to overview] | Viral Load (HCV RNA) at All Visits During Treatment and Follow-up |
| NCT00984620 (16) [back to overview] | Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (6) |
| NCT00984620 (16) [back to overview] | Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (5) |
| NCT00984620 (16) [back to overview] | End of Treatment Response (ETR) |
| NCT00984620 (16) [back to overview] | Rapid Virological Response at Week 4 (RVR) |
| NCT00984620 (16) [back to overview] | Virological Response at Week 24 (W24VR) |
| NCT00984620 (16) [back to overview] | Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (4) |
| NCT00984620 (16) [back to overview] | Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (3) |
| NCT00984620 (16) [back to overview] | Sustained Virological Response (SVR24) at 24 Weeks After Completion of All Therapy |
| NCT00984620 (16) [back to overview] | Virological Response at Week 28 (W28VR) |
| NCT00984620 (16) [back to overview] | Virological Response at Week 36 (W36VR) |
| NCT00984620 (16) [back to overview] | Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (2) |
| NCT00984620 (16) [back to overview] | Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (1) |
| NCT00991289 (11) [back to overview] | Percent Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) From Study Entry |
| NCT00991289 (11) [back to overview] | Change in Hemoglobin Level From Study Entry |
| NCT00991289 (11) [back to overview] | Number of Participants With Adverse Events of Grade 2 or Higher |
| NCT00991289 (11) [back to overview] | Number of Participants With HCV Genotype 1 |
| NCT00991289 (11) [back to overview] | Percentage of Participants With Complete Early Virologic Response (cEVR) |
| NCT00991289 (11) [back to overview] | Percentage of Participants With Early Virologic Response (EVR) |
| NCT00991289 (11) [back to overview] | Percent Change in Fasting Insulin Level From Study Entry |
| NCT00991289 (11) [back to overview] | Change in log10 HCV Viral Load After 4 Weeks of Nitazoxanide (NTZ) Monotherapy. |
| NCT00991289 (11) [back to overview] | Percentage of Participants With Sustained Virologic Response (SVR) |
| NCT00991289 (11) [back to overview] | Percent Change in Fasting Glucose Level From Study Entry |
| NCT00991289 (11) [back to overview] | Percentage of Participants With Rapid Virologic Response (RVR) |
| NCT01054573 (10) [back to overview] | Percentage of Participants Achieving Extended Rapid Virologic Response (eRVR) |
| NCT01054573 (10) [back to overview] | Percentage of Participants Who Relapsed During Follow-Up |
| NCT01054573 (10) [back to overview] | The Percentage of Participants Achieving a Sustained Virologic Response (SVR) 24 Weeks After the Last Dose of Study Drug (SVR24 Actual) |
| NCT01054573 (10) [back to overview] | Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level |
| NCT01054573 (10) [back to overview] | Percentage of Participants Who Met a Virologic Stopping Rule That Required Them to Permanently Discontinue Telaprevir and Continue Pegylated Interferon (Peg-IFN) and Ribavirin (RBV) at Week 4 or Week 8 |
| NCT01054573 (10) [back to overview] | Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values Over Time |
| NCT01054573 (10) [back to overview] | Percentage of Participants Who Met a Virologic Stopping Rule That Required Them to Permanently Discontinue All Study Drugs at Week 12, 24, or 36 |
| NCT01054573 (10) [back to overview] | Percentage of Participants With Viral Breakthrough |
| NCT01054573 (10) [back to overview] | Percentage of Participants Achieving Rapid Virologic Response (RVR) |
| NCT01054573 (10) [back to overview] | The Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected at Different Time Points |
| NCT01058005 (1) [back to overview] | Incidence of Treatment-emergent Serious Adverse Events (SAEs) |
| NCT01064401 (5) [back to overview] | Proportion of Participants Relapse-free at Week 144 |
| NCT01064401 (5) [back to overview] | Percentage of Participants With a ≥ 7.5 Point Worsening From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Impact Score at 96 Weeks |
| NCT01064401 (5) [back to overview] | Adjusted Mean Number of New or Newly Enlarging T2 Hyperintense Lesions up to Week 96 |
| NCT01064401 (5) [back to overview] | Adjusted Annualized Relapse Rate (ARR) |
| NCT01064401 (5) [back to overview] | Proportion of Participants With Sustained Disability Progression at 144 Weeks |
| NCT01071083 (2) [back to overview] | Time Course to Return of Radiological and/or Clinical Evidence of Multiple Sclerosis Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) and/or Clinical Relapse Rescue Criteria. |
| NCT01071083 (2) [back to overview] | Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria. |
| NCT01075763 (9) [back to overview] | Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score |
| NCT01075763 (9) [back to overview] | Global Deterioration Scale Score |
| NCT01075763 (9) [back to overview] | Geriatric Depression Scale (GDS) Score |
| NCT01075763 (9) [back to overview] | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score |
| NCT01075763 (9) [back to overview] | Mini Mental Status Examination (MMSE) Score |
| NCT01075763 (9) [back to overview] | Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score |
| NCT01075763 (9) [back to overview] | Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score |
| NCT01075763 (9) [back to overview] | Instrumental Activities of Daily Living (IADL) Score |
| NCT01075763 (9) [back to overview] | Physical Self-Maintenance Scale (PSMS) Score |
| NCT01095835 (11) [back to overview] | Percentage of Participants With HBV-DNA Lowering to <3,400 IU/mL and to < 2,000 IU/mL |
| NCT01095835 (11) [back to overview] | Percentage of Participants With ALT Normalization |
| NCT01095835 (11) [back to overview] | Percentage of Participants Achieving Combined Response Using a Cut-Off for HBV-DNA Levels to 2,000 IU/mL |
| NCT01095835 (11) [back to overview] | Change From Baseline of Quantitative Hepatitis B Surface Antigen (HbsAg) Level at the End of Treatment |
| NCT01095835 (11) [back to overview] | Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period |
| NCT01095835 (11) [back to overview] | Percentage of Participants Achieving Histological Response |
| NCT01095835 (11) [back to overview] | Percentage of Participants With Lamivudine Genotype Resistance During PEG-IFN+LAM96 Combined Therapy |
| NCT01095835 (11) [back to overview] | Percentage of Participants With Loss of Hepatitis B Surface Antigen (HbsAg) and Hepatitis B Surface Antibodies (Anti-HBs) Seroconversion |
| NCT01095835 (11) [back to overview] | Percentage of Participants With HBV-DNA Below Limit of Quantification |
| NCT01095835 (11) [back to overview] | Percentage of Participants Achieving the Combined Response at the End of Treatment |
| NCT01095835 (11) [back to overview] | Percentage of Participants Achieving the Combined Response at 24 Weeks of Follow-up |
| NCT01100528 (2) [back to overview] | Number of Patients With Disease-free Survival (DFS) |
| NCT01100528 (2) [back to overview] | Number of Participants With Toxicity or Grade 4 Adverse Events Via CTCAE Version 3.0 |
| NCT01125189 (7) [back to overview] | Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Sustained Virologic Response (SVR24) |
| NCT01125189 (7) [back to overview] | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died |
| NCT01125189 (7) [back to overview] | Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Extended Rapid Virologic Response (eRVR) |
| NCT01125189 (7) [back to overview] | Percentage of Resistant Variants Associated With Virologic Failure |
| NCT01125189 (7) [back to overview] | Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Rapid Virologic Response (RVR) |
| NCT01125189 (7) [back to overview] | Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With 12-week Sustained Virologic Response (SVR12) |
| NCT01125189 (7) [back to overview] | Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Complete Early Virologic Response (cEVR) |
| NCT01142466 (6) [back to overview] | Number of Relapse-free Participants |
| NCT01142466 (6) [back to overview] | Time From Baseline to First Multiple Sclerosis Relapse (in Weeks) |
| NCT01142466 (6) [back to overview] | Absolute Changes in the Number of T1 Lesions From Baseline to Week 24, 48, 72 and 96 |
| NCT01142466 (6) [back to overview] | Absolute Changes in the Number of T2 Lesions From Baseline to Week 24, 48, 72 and 96 |
| NCT01142466 (6) [back to overview] | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) |
| NCT01142466 (6) [back to overview] | Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96 |
| NCT01144052 (8) [back to overview] | Number of Days Until First On-study Relapse |
| NCT01144052 (8) [back to overview] | Proportion of Relapse Free Patients |
| NCT01144052 (8) [back to overview] | Number of Patients With Adverse Events |
| NCT01144052 (8) [back to overview] | MRI Parameters |
| NCT01144052 (8) [back to overview] | Severity of Relapses |
| NCT01144052 (8) [back to overview] | Number of Infections |
| NCT01144052 (8) [back to overview] | Number of Participants With Relapses |
| NCT01144052 (8) [back to overview] | Number of Relapses |
| NCT01158534 (5) [back to overview] | Objective Response Rate Assessed by RECIST Criteria. |
| NCT01158534 (5) [back to overview] | Progression-free Survival |
| NCT01158534 (5) [back to overview] | Overall Survival |
| NCT01158534 (5) [back to overview] | Number of Patients With Statistically Significant Change in Cellular Immune Parameters From Baseline to 2 Months |
| NCT01158534 (5) [back to overview] | Duration of Response |
| NCT01180790 (11) [back to overview] | Segment 2: Complete Early Virologic Response (cEVR) |
| NCT01180790 (11) [back to overview] | Segment 2: RVR4 |
| NCT01180790 (11) [back to overview] | Segment 1: Rapid Viral Response At Week 4 (RVR4) |
| NCT01180790 (11) [back to overview] | Segment 1: Safety |
| NCT01180790 (11) [back to overview] | Segment 1: cEVR |
| NCT01180790 (11) [back to overview] | Segment 2: Safety |
| NCT01180790 (11) [back to overview] | Segment 1 And Segment 2: End Of Treatment Response |
| NCT01180790 (11) [back to overview] | Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24) |
| NCT01180790 (11) [back to overview] | Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12) |
| NCT01180790 (11) [back to overview] | Segment 1 And Segment 2: HCV RNA Change From Baseline |
| NCT01180790 (11) [back to overview] | Segment 1 And Segment 2: HCV RNA Change From Baseline |
| NCT01185028 (3) [back to overview] | Number of Participants With Adverse Events |
| NCT01185028 (3) [back to overview] | Sustained Viral Response Rate |
| NCT01185028 (3) [back to overview] | Tolerability of Study Drug Measured as Discontinuation. |
| NCT01192698 (1) [back to overview] | HCV RNA Result |
| NCT01198132 (10) [back to overview] | Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L) |
| NCT01198132 (10) [back to overview] | Number of Relapse-Free (Documented) Subjects |
| NCT01198132 (10) [back to overview] | Mean Number of Relapses Per Subject |
| NCT01198132 (10) [back to overview] | Cumulative Probability of Progression of Disability (Kaplan-Meier Curves) |
| NCT01198132 (10) [back to overview] | Annualized Relapse Rate |
| NCT01198132 (10) [back to overview] | Time to First Documented Relapse |
| NCT01198132 (10) [back to overview] | Number of New or Extended Lesions by T1- and T2-Weighted Magnetic Resonance Imaging (MRI) |
| NCT01198132 (10) [back to overview] | Changes From Baseline in Measured Lesion Load (T2) |
| NCT01198132 (10) [back to overview] | Change From Baseline in Measurement and Evaluation of Cognitive Ability by Paced Auditory Serial Addition Task (PASAT) Total Score At Week 96 |
| NCT01198132 (10) [back to overview] | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Abnormal Clinical Laboratory |
| NCT01201343 (8) [back to overview] | Change From Baseline in Emotional Dyscontrol Sub-score of the EHD Scale at Month 18 |
| NCT01201343 (8) [back to overview] | Change From Baseline in Emotional Dyscontrol Sub-score of the EHD Scale at Month 24 |
| NCT01201343 (8) [back to overview] | Change From Baseline in Center for Epidemiologic Studies Depression (CES-D) Score at Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24 |
| NCT01201343 (8) [back to overview] | Change From Baseline in Center for State-trait Anger Expression Inventory 2 (STAXI-state) Score at Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24 |
| NCT01201343 (8) [back to overview] | Change From Baseline in Emotional Abrasion Sub-score of the EHD Scale at Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24 |
| NCT01201343 (8) [back to overview] | Change From Baseline in Emotional Dyscontrol Sub-score of the Depressive Mood Scale (Echelle d'Humeur Depressive [EHD]) Scale at Month 12 |
| NCT01201343 (8) [back to overview] | Change From Baseline in Fatigue Score at Months 1, 2, 3, 6, 12 and 24 |
| NCT01201343 (8) [back to overview] | Change From Baseline in State-trait Anxiety Inventory (STAI State) Score at Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24 |
| NCT01241760 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After the Last Planned Dose of Study Drugs (SVR12 Planned) |
| NCT01241760 (7) [back to overview] | Percentage of Participants With On-treatment Virologic Failure Which Required Them to Permanently Discontinue All Study Drugs |
| NCT01241760 (7) [back to overview] | Percentage of Participants Who Relapsed During Follow-up Period |
| NCT01241760 (7) [back to overview] | Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points. |
| NCT01241760 (7) [back to overview] | Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned) |
| NCT01241760 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response 72 Weeks After the Start of Study Medication (SVR72 Planned) |
| NCT01241760 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response 24 Weeks After the Last Planned Dose of Study Drugs (SVR24 Planned) |
| NCT01247324 (14) [back to overview] | Number of T1 Hypointense Lesions During the Double-Blind Treatment |
| NCT01247324 (14) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT01247324 (14) [back to overview] | Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double Blind Treatment |
| NCT01247324 (14) [back to overview] | Exposure to Ocrelizumab (Area Under the Concentration - Time Curve, AUC) |
| NCT01247324 (14) [back to overview] | Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks |
| NCT01247324 (14) [back to overview] | Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96 |
| NCT01247324 (14) [back to overview] | Number of T1 Gadolinium (Gd)-Enhancing Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double-Blind Treatment |
| NCT01247324 (14) [back to overview] | Percentage of Participants Who Have No Evidence of Disease Activity (NEDA) up to Week 96 |
| NCT01247324 (14) [back to overview] | Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks |
| NCT01247324 (14) [back to overview] | Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks During the Double-Blind Treatment Period |
| NCT01247324 (14) [back to overview] | Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks During the Double-Blind Treatment Period |
| NCT01247324 (14) [back to overview] | Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score to Week 96 |
| NCT01247324 (14) [back to overview] | Change From Baseline in Short Form Health Survey-36 (SF-36) Physical Component Summary (PCS) Score at Week 96 |
| NCT01247324 (14) [back to overview] | Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab |
| NCT01252355 (7) [back to overview] | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) |
| NCT01252355 (7) [back to overview] | Time to Relapse: Kaplan-Meier Estimates of the Probability of no Relapse at Week 24, 48, and 72 |
| NCT01252355 (7) [back to overview] | Brain MRI Assessment: Volume of Gd-enhancing T1-lesions Per MRI Scan |
| NCT01252355 (7) [back to overview] | Brain MRI Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) at Week 24 |
| NCT01252355 (7) [back to overview] | Overview of Adverse Events (AEs) |
| NCT01252355 (7) [back to overview] | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per Scan (Poisson Regression Estimates) |
| NCT01252355 (7) [back to overview] | Annualized Relapse Rate (ARR) (Poisson Regression Estimates) |
| NCT01257204 (12) [back to overview] | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 3 |
| NCT01257204 (12) [back to overview] | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 3 |
| NCT01257204 (12) [back to overview] | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period |
| NCT01257204 (12) [back to overview] | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period |
| NCT01257204 (12) [back to overview] | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 |
| NCT01257204 (12) [back to overview] | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 |
| NCT01257204 (12) [back to overview] | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 2 |
| NCT01257204 (12) [back to overview] | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 3 |
| NCT01257204 (12) [back to overview] | Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 2 |
| NCT01257204 (12) [back to overview] | Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 3 |
| NCT01257204 (12) [back to overview] | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 2 |
| NCT01257204 (12) [back to overview] | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 2 |
| NCT01259856 (6) [back to overview] | Change in the Total Symptom Score (TSS) |
| NCT01259856 (6) [back to overview] | Number of Participants With Progression of Disease or Death |
| NCT01259856 (6) [back to overview] | Number of Participants With Complete Remission (CR) |
| NCT01259856 (6) [back to overview] | Number of Participants With Grade 3 and Grade 4 Hematological and Non-hematological Events |
| NCT01259856 (6) [back to overview] | Number of Participants With Partial Remission (PR) |
| NCT01259856 (6) [back to overview] | Number of Participants With Major Cardiovascular Events After Therapy |
| NCT01274338 (7) [back to overview] | Change in FACT-G (Functional Assessment of Cancer Therapy - General) Total Score From Baseline to 3 Months |
| NCT01274338 (7) [back to overview] | Recurrence-free Survival (RFS; Arm A [HIP] vs. Arm B [HDI]) |
| NCT01274338 (7) [back to overview] | Recurrence-free Survival (RFS; Arm B [HDI] vs. Arm C [LIP]) |
| NCT01274338 (7) [back to overview] | Change in FACT-BRM (Functional Assessment of Cancer Therapy - Biologic Response Modifiers) Total Score From Baseline to 3 Months |
| NCT01274338 (7) [back to overview] | Change in FACIT-D (Functional Assessment of Cancer Therapy - Diarrhea) Diarrhea Subscale Score From Baseline to 3 Months |
| NCT01274338 (7) [back to overview] | 5-year Overall Survival (OS) Rate (Arm B [HDI] vs. Arm C [LIP]) |
| NCT01274338 (7) [back to overview] | 5-year Overall Survival (OS) Rate (Arm A [HIP] vs. Arm B [HDI]) |
| NCT01276756 (5) [back to overview] | End-of-treatment Response |
| NCT01276756 (5) [back to overview] | Sustained Virologic Response |
| NCT01276756 (5) [back to overview] | Rapid Virological Response |
| NCT01276756 (5) [back to overview] | Safety of Nitazoxanide (Number of Participants Experiencing Adverse Events) |
| NCT01276756 (5) [back to overview] | Early Virological Response |
| NCT01280656 (13) [back to overview] | Percentage of Participants With Sustained Virologic Response Treated at Interferon Application Centers and Treated at Home |
| NCT01280656 (13) [back to overview] | Percentage of Participants With Virologic Response at End of Treatment |
| NCT01280656 (13) [back to overview] | Mean Percentage Reduction of Hemoglobin in Treatment Responders and Treatment Non-Responders |
| NCT01280656 (13) [back to overview] | Percentage of Participants Who Were Treated at Interferon Application Centers and at Home and Discontinued Treatment |
| NCT01280656 (13) [back to overview] | Percentage of Participants With Early Virologic Response at Week 12 |
| NCT01280656 (13) [back to overview] | Number of Participants With Any Adverse Events and Any Serious Adverse Events |
| NCT01280656 (13) [back to overview] | Percentage of Participants With Virologic Relapse up to Week 72 |
| NCT01280656 (13) [back to overview] | Percentage of Participants With Sustained Virologic Response at 24 Weeks After End of Treatment |
| NCT01280656 (13) [back to overview] | Percentage of Participants With Sustained Virologic Response at 12 Weeks After End of Treatment |
| NCT01280656 (13) [back to overview] | Percentage of Participants With Rapid Virologic Response at Week 4 |
| NCT01280656 (13) [back to overview] | Percentage of Participants With Null Response or No Responder at End of Treatment |
| NCT01280656 (13) [back to overview] | Percentage of Participants Who Discontinued Treatment Due to Adverse Events |
| NCT01280656 (13) [back to overview] | Number of Participants With Interferon Dose Reduction Rates in Function of the Interferon Type Being Used |
| NCT01285401 (17) [back to overview] | Mean Change From Baseline in the Total Volume of T1 Hypo Intense Lesions at Week 48 |
| NCT01285401 (17) [back to overview] | Mean Change From Baseline in the Total Volume of T2 Lesions at Week 48 (T2 Burden of Disease) |
| NCT01285401 (17) [back to overview] | Total Number of Reported Relapses at All Time Points up to 48 Weeks |
| NCT01285401 (17) [back to overview] | Percentage of Subjects With Disease Activity Free Status (Alternate Definition) at Week 48 |
| NCT01285401 (17) [back to overview] | Mean Number of Combined Unique Active (CUA) Lesions Per Subject Per Scan at Week 48 |
| NCT01285401 (17) [back to overview] | Number od Subjects With Confirmed EDSS Progression |
| NCT01285401 (17) [back to overview] | Percentage of Subjects With Disease Activity Free Status up to Week 48 |
| NCT01285401 (17) [back to overview] | Number of Subjects With Relapse |
| NCT01285401 (17) [back to overview] | Annualized Relapse Rate at Week 48 |
| NCT01285401 (17) [back to overview] | Percentage of Subjects Free From New T1 Hypointense Lesions (Black Holes) at Week 48 |
| NCT01285401 (17) [back to overview] | Percentage of Subjects Free From T1 Gadolinium Enhancing Lesions at Week 48 |
| NCT01285401 (17) [back to overview] | Percentage of Subjects Treated With Glucocorticoids Due to Relapses |
| NCT01285401 (17) [back to overview] | Cumulative Number of New Combined Unique Active (CUA) Lesions at Week 48 |
| NCT01285401 (17) [back to overview] | Percentage of Subjects Free From Any Expanded Disability Status Scale (EDSS) Progression at Week 48 |
| NCT01285401 (17) [back to overview] | Percentage of Relapse-free Subjects at Week 48 |
| NCT01285401 (17) [back to overview] | Cumulative Number of Relaxation Time 1 (T1) Gadolinium Enhancing Lesions at Week 48 |
| NCT01285401 (17) [back to overview] | Percentage of New T1 Hypointense Lesions (Black Holes) at Week 48 Within the Subgroup of New or Enlarging Non-enhancing T2 Lesions |
| NCT01290731 (9) [back to overview] | The Number of Participants Demonstrating Viral Relapse |
| NCT01290731 (9) [back to overview] | Area Under the Plasma Concentration-time Curve From 0 to 24 Hrs (AUC24h) for TMC435 |
| NCT01290731 (9) [back to overview] | The Number of Participants With Viral Breakthrough |
| NCT01290731 (9) [back to overview] | Plasma Concentrations of TMC435 |
| NCT01290731 (9) [back to overview] | The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT) |
| NCT01290731 (9) [back to overview] | The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up |
| NCT01290731 (9) [back to overview] | The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT) |
| NCT01290731 (9) [back to overview] | The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) |
| NCT01290731 (9) [back to overview] | The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) |
| NCT01295515 (5) [back to overview] | Pre- and Post- Interferon Alpha on Human Immunodeficiency Virus Type 1 (HIV-1) Deoxyribonucleic Acid (DNA) |
| NCT01295515 (5) [back to overview] | Fold Change in Ribonucleic Acid (RNA) and Deoxyribonucleic Acid (DNA) in Human Immunodeficiency Virus Type 1 (HIV-1) Genetic Variation in Individuals Undergoing Interferon Therapy |
| NCT01295515 (5) [back to overview] | Count of Participants With Serious and Non-serious Adverse Events Assessed by the Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading Adult Adverse Events. |
| NCT01295515 (5) [back to overview] | Pre-and Post- Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) in HIV-infected Individuals |
| NCT01295515 (5) [back to overview] | Pre- and Post- Interferon Alpha on Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) |
| NCT01314261 (12) [back to overview] | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-267 |
| NCT01314261 (12) [back to overview] | Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing |
| NCT01314261 (12) [back to overview] | Time to Maximum Plasma Concentration (Tmax) of ABT-267 |
| NCT01314261 (12) [back to overview] | Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing |
| NCT01314261 (12) [back to overview] | Median Time to Suppression of Hepatitis C Virus Ribonucleic Acid (HCV RNA) |
| NCT01314261 (12) [back to overview] | Percentage of Participants With Partial Early Virologic Response (pEVR) |
| NCT01314261 (12) [back to overview] | Percentage of Participants With Extended Rapid Virologic Response (eRVR) |
| NCT01314261 (12) [back to overview] | Serum Concentrations of Pegylated Interferon (pegIFN) |
| NCT01314261 (12) [back to overview] | Percentage of Participants With Complete Early Virologic Response (cEVR) |
| NCT01314261 (12) [back to overview] | Plasma Concentrations of Ribavirin (RBV) |
| NCT01314261 (12) [back to overview] | Percentage of Participants With 4-week Rapid Virologic Response (RVR) |
| NCT01314261 (12) [back to overview] | Maximum Plasma Concentration (Cmax) of ABT-267 |
| NCT01332019 (39) [back to overview] | Number of New T1 Hypointense Lesions |
| NCT01332019 (39) [back to overview] | Number of Participants Experiencing Adverse Events (AEs) Serious AEs, and Discontinuations Due to AEs |
| NCT01332019 (39) [back to overview] | Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities |
| NCT01332019 (39) [back to overview] | Number of Participants With Shifts From Baseline: Kidney Function and Other Blood Chemistry |
| NCT01332019 (39) [back to overview] | Number of Gd-Enhancing Lesions |
| NCT01332019 (39) [back to overview] | Number of Participants With Shifts From Baseline: Liver Function Laboratory Values |
| NCT01332019 (39) [back to overview] | Number of Participants With Shifts From Baseline: Urinalysis |
| NCT01332019 (39) [back to overview] | Percentage Change of Whole Brain Volume |
| NCT01332019 (39) [back to overview] | Percentage of Participants Who Relapsed |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: How Convenient or Inconvenient Is It to Take Your Medication as Instructed? |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: How Convenient or Inconvenient Is It to Take Your Medication Every 2 Weeks? |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: How Likely Would You Be to Continue to Use This Medication? |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: How Satisfied or Dissatisfied Are You With the Injection Frequency (Every 2 Weeks)? |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: How Tolerable or Intolerable Do You Find the Medication? |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: I Am Satisfied With the Dosing Frequency of This Medication. |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: Main Reason for Missed Injections |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: Over the Past 4 Weeks, Did You Miss Any of Your Injections? |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: Overall, How Satisfied or Dissatisfied Are You With This Medication? |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: The Twice a Month Dosing Enables Me to Be More Spontaneous and Flexible. |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: The Twice a Month Dosing Makes It More Convenient for Me to Travel/Vacation. |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: This Medication Enables Me to Focus More on Myself and My Family Rather Than My MS. |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: This Medication Improves My Self-Confidence and Self-Reliance. |
| NCT01332019 (39) [back to overview] | Summary of Participant-Reported Treatment Satisfaction: This Medication Makes It Easy For Me to Carry Out My Daily Responsibilities. |
| NCT01332019 (39) [back to overview] | Time to Sustained Disability Progression |
| NCT01332019 (39) [back to overview] | Volume of Gd-Enhancing Lesions |
| NCT01332019 (39) [back to overview] | Volume of T1 Hypointense Lesions |
| NCT01332019 (39) [back to overview] | Volume of T2 Hyperintense Lesions |
| NCT01332019 (39) [back to overview] | Change From Baseline in Euro Quality of Life (EQ-5D) Index Score |
| NCT01332019 (39) [back to overview] | Change From Baseline in EQ-5D Visual Analogue Scale (VAS) |
| NCT01332019 (39) [back to overview] | Change From Baseline in 12-Item Short Form Health Survey (SF-12) Mental Component Score (MCS) |
| NCT01332019 (39) [back to overview] | Number of Relapses Requiring IV Steroid Use |
| NCT01332019 (39) [back to overview] | Number of MS-Related Hospitalizations |
| NCT01332019 (39) [back to overview] | Annualized Relapse Rate (ARR) |
| NCT01332019 (39) [back to overview] | Change From Baseline in Expanded Disability Status Scale (EDSS) |
| NCT01332019 (39) [back to overview] | Change From Baseline in Multiple Sclerosis Impact Scale (MSIS)-29 Physical Score |
| NCT01332019 (39) [back to overview] | Change From Baseline in SF-12 Physical Component Score (PCS) |
| NCT01332019 (39) [back to overview] | Change From Baseline in Symbol Digit Modalities Test (SDMT) |
| NCT01332019 (39) [back to overview] | Number of New Active Lesions |
| NCT01332019 (39) [back to overview] | Number of New or Newly Enlarging T2 Hyperintense Lesions |
| NCT01333501 (21) [back to overview] | Change From Screening in Spatial Recall Test (SPART) Raw Score |
| NCT01333501 (21) [back to overview] | Change From Screening in the Volume of Total T1 Hypointense Lesions |
| NCT01333501 (21) [back to overview] | Change From Screening in the Percentage of Brain Volume Change |
| NCT01333501 (21) [back to overview] | Change From Screening in Word List Generation (WLG) |
| NCT01333501 (21) [back to overview] | Change From Screening in the Volume of Total T2 Lesions |
| NCT01333501 (21) [back to overview] | Change From Screening in Selective Reminding Test - Delayed Recall (SRT-D) Raw Score |
| NCT01333501 (21) [back to overview] | Change From Screening in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw Score |
| NCT01333501 (21) [back to overview] | Change From Screening in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw Score |
| NCT01333501 (21) [back to overview] | Change From Screening in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw Score |
| NCT01333501 (21) [back to overview] | Change From Screening in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score- Card Set 1+2 |
| NCT01333501 (21) [back to overview] | Change From Screening in Montgomery-Asberg Depression Rating Scale (MADRS) |
| NCT01333501 (21) [back to overview] | Change From Screening in the Number of New T2 Lesions |
| NCT01333501 (21) [back to overview] | Change From Screening in Symbol Digit Modalities Test (SDMT) Raw Score |
| NCT01333501 (21) [back to overview] | Change From Screening in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2 |
| NCT01333501 (21) [back to overview] | Change From Screening in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort- Card Set 1+2 |
| NCT01333501 (21) [back to overview] | Changes in Quality of Life, by Means of the Multiple Sclerosis Quality of Life (MSQoL-54) |
| NCT01333501 (21) [back to overview] | Change From Screening in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw Score |
| NCT01333501 (21) [back to overview] | Change From Screening in the Number of T1 Gd+ Enhancing Lesions |
| NCT01333501 (21) [back to overview] | Change From Screening in Spatial Recall Test - Delayed Recall (SPART-D) |
| NCT01333501 (21) [back to overview] | Changes From Baseline in Fatigue Impact Scale (mFIS, Total Score and Scores of the 3 Individual Domains). |
| NCT01333501 (21) [back to overview] | Changes in the Environmental Status Scale Score (ESS) |
| NCT01353911 (8) [back to overview] | Median Time to First Achievement of Undetectable HCV RNA During Treatment |
| NCT01353911 (8) [back to overview] | Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days |
| NCT01353911 (8) [back to overview] | Percentage of Participants Achieving Complete Early Viral Response (cEVR) |
| NCT01353911 (8) [back to overview] | Percentage of Participants Achieving Rapid Viral Response (RVR) |
| NCT01353911 (8) [back to overview] | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12) |
| NCT01353911 (8) [back to overview] | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24) |
| NCT01353911 (8) [back to overview] | Percentage of Participants Achieving Undetectable HCV RNA at Week 72 |
| NCT01353911 (8) [back to overview] | Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days |
| NCT01355289 (4) [back to overview] | Change From Baseline of Local Platelet Count by Visit During Treatment Period A1 of Core Study |
| NCT01355289 (4) [back to overview] | Number of Participants Who Initiated Antiviral Treatment by Day 21 of Period A1 of Core Study |
| NCT01355289 (4) [back to overview] | Number of Participants Who Achieved Platelet Response (Greater Than or Equal to 100 x 10^9/L) by Day 21 of Treatment Period A1 of Core Study |
| NCT01355289 (4) [back to overview] | Number of Participants Who Achieved Platelet Count Greater Than 30 X 10^9/L From Baseline to Day 21 During Treatment Period A1 of Core Study |
| NCT01358864 (11) [back to overview] | AST Normalisation: AST in Normal Range 12 Weeks Post Treatment, When SVR12=NO |
| NCT01358864 (11) [back to overview] | ALT Normalisation: ALT in Normal Range 12 Weeks Post Treatment, SVR12=YES |
| NCT01358864 (11) [back to overview] | AST Normalisation: AST in Normal Range at End of Treatment, When SVR12=YES |
| NCT01358864 (11) [back to overview] | Early Treatment Success (ETS) |
| NCT01358864 (11) [back to overview] | Virological Response After 24 Weeks of Treatment Discontinuation (SVR24) |
| NCT01358864 (11) [back to overview] | ALT Normalisation: ALT in Normal Range 12 Weeks Post Treatment, When SVR12=NO |
| NCT01358864 (11) [back to overview] | ALT Normalisation: ALT in Normal Range at End of Treatment, When SVR12=NO |
| NCT01358864 (11) [back to overview] | ALT Normalisation: ALT in Normal Range at End of Treatment, When SVR12=YES |
| NCT01358864 (11) [back to overview] | AST Normalisation: AST in Normal Range at End of Treatment, When SVR12=NO |
| NCT01358864 (11) [back to overview] | AST Normalisation: AST in Normal Range 12 Weeks Post Treatment, SVR12=YES |
| NCT01358864 (11) [back to overview] | Sustained Virological Response 12 Weeks Post Treatment (SVR12) |
| NCT01359956 (4) [back to overview] | Overall Response Rate (ORR) |
| NCT01359956 (4) [back to overview] | Progression Free Survival (PFS) |
| NCT01359956 (4) [back to overview] | Treatment Related Toxicity |
| NCT01359956 (4) [back to overview] | Overall Survival (OS) |
| NCT01364090 (1) [back to overview] | Treatment Efficacy |
| NCT01376362 (17) [back to overview] | Change in Intraocular Pressure (IOP) in the Fellow Eye at Week One Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in Intraocular Pressure (IOP) in the Fellow Eye at Week Two Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in Intraocular Pressure (IOP) in the Study Eye at Week One Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in Intraocular Pressure (IOP) in the Study Eye at Week Two Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline |
| NCT01376362 (17) [back to overview] | Proportion of Participants With a Visual Loss of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in the Study Eye |
| NCT01376362 (17) [back to overview] | Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week Two Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week One Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week One Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week Two Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline |
| NCT01376362 (17) [back to overview] | Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline |
| NCT01389323 (5) [back to overview] | Percentage of Participants Achieving Sustained Virologic Response at Post-treatment Week 12 (SVR12) With rs12979860 Single Nucleotide Polymorphisms at Baseline in the Interleukin-28B Gene |
| NCT01389323 (5) [back to overview] | Percentage of Participants With Hepatitis C Virus (HCV) RNA Levels |
| NCT01389323 (5) [back to overview] | Percentage of Participants With Hepatitis C Virus (HCV) RNA Levels |
| NCT01389323 (5) [back to overview] | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Treatment-related AEs, and Who Died |
| NCT01389323 (5) [back to overview] | Percentage of Participants Achieving Sustained Virologic Response at Post-treatment Week 12 (SVR12) |
| NCT01403376 (5) [back to overview] | Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination |
| NCT01403376 (5) [back to overview] | Percentage of Participants With 2 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination |
| NCT01403376 (5) [back to overview] | Immunoglobulin Levels |
| NCT01403376 (5) [back to overview] | Percentage of Participants With 4 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination |
| NCT01403376 (5) [back to overview] | Percentage of Participants With Antibody Titer ≥40 at 28 Days Post Vaccination |
| NCT01404936 (1) [back to overview] | Participants' Response |
| NCT01405027 (5) [back to overview] | Drug Exposure |
| NCT01405027 (5) [back to overview] | Determination of the Rate of Sustained Viral Response (SVR) for HCV Patients Treated With Boceprevir, Peginterferon and Ribavirin at Community Sites and at HCEEs. |
| NCT01405027 (5) [back to overview] | Treatment Duration Compliance Rate |
| NCT01405027 (5) [back to overview] | Number of Participants With Adverse Events |
| NCT01405027 (5) [back to overview] | Short Form Health Survey Measuring Quality of Life Reported at Baseline, End of Treatment, and Follow-up Week 24 (36 Multiple Choice Questions) |
| NCT01412333 (14) [back to overview] | Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab |
| NCT01412333 (14) [back to overview] | Change From Baseline in Short Form Health Survey-36 (SF-36) Physical Component Summary (PCS) Score at Week 96 |
| NCT01412333 (14) [back to overview] | Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score to Week 96 |
| NCT01412333 (14) [back to overview] | Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks During the Double-Blind Treatment Period |
| NCT01412333 (14) [back to overview] | Percentage of Participants Who Have No Evidence of Disease Activity (NEDA) up to Week 96 |
| NCT01412333 (14) [back to overview] | Exposure to Ocrelizumab (Area Under the Concentration - Time Curve, AUC) |
| NCT01412333 (14) [back to overview] | Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double Blind Treatment |
| NCT01412333 (14) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT01412333 (14) [back to overview] | Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks |
| NCT01412333 (14) [back to overview] | Number of T1 Gadolinium (Gd)-Enhancing Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double-Blind Treatment |
| NCT01412333 (14) [back to overview] | Number of T1 Hypointense Lesions During the Double-Blind Treatment |
| NCT01412333 (14) [back to overview] | Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96 |
| NCT01412333 (14) [back to overview] | Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks |
| NCT01412333 (14) [back to overview] | Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks During the Double-Blind Treatment Period |
| NCT01428063 (8) [back to overview] | Percentage of Participants Other Than Genotype 1 With Sustained Virologic Response at Post Treatment Week 12 (SVR12) |
| NCT01428063 (8) [back to overview] | Percentage of Participants With Complete Early Virologic Response (cEVR) |
| NCT01428063 (8) [back to overview] | Percentage of Participants With End of the Treatment Response (EOTR) |
| NCT01428063 (8) [back to overview] | Percentage of Participants With Extended Rapid Virologic Response (eRVR) |
| NCT01428063 (8) [back to overview] | Percentage of Participants With Rapid Virologic Response (RVR) at Post Treatment Week 4 |
| NCT01428063 (8) [back to overview] | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) |
| NCT01428063 (8) [back to overview] | Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) for All Nonresponders With Genotype 1 Hepatitis C Virus (HCV) |
| NCT01428063 (8) [back to overview] | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Who Died During the Study |
| NCT01439373 (21) [back to overview] | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 |
| NCT01439373 (21) [back to overview] | Median Time of Maximal Plasma Concentration (Tmax) of GSK2336805 and Lag Time Before First Observation of Quantifiable Concentration (Tlag) at Day 1 |
| NCT01439373 (21) [back to overview] | Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis |
| NCT01439373 (21) [back to overview] | Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses) |
| NCT01439373 (21) [back to overview] | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period |
| NCT01439373 (21) [back to overview] | Number of Participants With HCV Genotype 1 With Virologic Response |
| NCT01439373 (21) [back to overview] | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 |
| NCT01439373 (21) [back to overview] | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 |
| NCT01439373 (21) [back to overview] | Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal |
| NCT01439373 (21) [back to overview] | Mean Apparent Clearance (CL/F) of GSK2336805 |
| NCT01439373 (21) [back to overview] | Number of Participants With Vital Signs of Potential Clinical Concern |
| NCT01439373 (21) [back to overview] | Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis |
| NCT01439373 (21) [back to overview] | Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses |
| NCT01439373 (21) [back to overview] | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale |
| NCT01439373 (21) [back to overview] | Change From Baseline in QTcF Interval at Day 2 and 28 |
| NCT01439373 (21) [back to overview] | Change From Baseline in Serum Alanine Aminotransferase Levels |
| NCT01439373 (21) [back to overview] | Mean Area Under the Concentration-time Curve (AUC[0-24]), AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK2336805, at Day 1 |
| NCT01439373 (21) [back to overview] | Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28 |
| NCT01439373 (21) [back to overview] | Mean Maximum Plasma Concentration of GSK2336805 (Cmax) and Concentration at 24 h (C24) at Day 1 |
| NCT01439373 (21) [back to overview] | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 |
| NCT01439373 (21) [back to overview] | Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28 |
| NCT01442779 (3) [back to overview] | Participants With Change in Cough |
| NCT01442779 (3) [back to overview] | Minimal/no Progression (1 yr) by High Resolution Computed Tomography (HRCT) & Pulmonary Function |
| NCT01442779 (3) [back to overview] | Minimal/no Change in Quality of Life |
| NCT01448044 (5) [back to overview] | Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) or Sustained Virologic Response at Follow-up Week 24 (SVR24) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene |
| NCT01448044 (5) [back to overview] | Percentage of Participants With Undetectable Hepatitis C Virus (HCV) RNA Levels |
| NCT01448044 (5) [back to overview] | Percentage of Participants Who Achieve HCV Ribonucleic Acid (RNA) < Limit of Quantification (LLOQ) |
| NCT01448044 (5) [back to overview] | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died |
| NCT01448044 (5) [back to overview] | Percentage of Participants With 12 Week Sustained Virologic Response (SVR12) |
| NCT01459913 (9) [back to overview] | Number of Subjects With Extended Rapid Viral Response (eRVR) |
| NCT01459913 (9) [back to overview] | Percentage of Subjects With Sustained Viral Response 4 Weeks After Last Planned Dose of Study Drug (SVR4) |
| NCT01459913 (9) [back to overview] | Percentage of Subjects With Viral Relapse |
| NCT01459913 (9) [back to overview] | Percentage of Subjects With Sustained Viral Response at Week 72 (SVR72) |
| NCT01459913 (9) [back to overview] | Percentage of Subjects With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) |
| NCT01459913 (9) [back to overview] | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT01459913 (9) [back to overview] | Number of Subjects With Rapid Viral Response (RVR) |
| NCT01459913 (9) [back to overview] | Percentage of Subjects With On-Treatment Virologic Failure |
| NCT01459913 (9) [back to overview] | Percentage of Subjects With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) |
| NCT01460875 (7) [back to overview] | Level of Activated STAT1(Phospho-STAT1) |
| NCT01460875 (7) [back to overview] | Effect of Dose-reduction on Interferon Alfa Gene Expression at Dose Level 4MU |
| NCT01460875 (7) [back to overview] | Effect of Dose-reduction on Expression of Interferon Alfa Stimulated Genes |
| NCT01460875 (7) [back to overview] | Effect of Dose-reduction on Interferon Alfa Gene Expression |
| NCT01460875 (7) [back to overview] | Effect of Dose-reduction on Interferon Alfa Gene Expression Through Marker CD69 |
| NCT01460875 (7) [back to overview] | Number of Patients With Adverse Events |
| NCT01460875 (7) [back to overview] | Percentage of Patients With Correlation Between STAT1 Phosphorylation and Interferon Alfa Gene Regulation |
| NCT01462773 (2) [back to overview] | Document Any Objective Anti-tumor Responses and Time to Tumor Progression That May Occur in Response to This Treatment Regimen. |
| NCT01462773 (2) [back to overview] | Determine Dose Limiting Toxicities (DLTs) of VELCADE When Administered in Combination With IFN-α-2b to Patients With Metastatic Malignant Melanoma. |
| NCT01467479 (8) [back to overview] | Percentage of Participants With Undetectable HCV RNA at End of Treatment (EOT) |
| NCT01467479 (8) [back to overview] | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24) |
| NCT01467479 (8) [back to overview] | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) |
| NCT01467479 (8) [back to overview] | Percentage of Participants With Rapid Viral Response (RVR) |
| NCT01467479 (8) [back to overview] | Percentage of Participants With Extended Rapid Viral Response (eRVR) |
| NCT01467479 (8) [back to overview] | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT01467479 (8) [back to overview] | Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region |
| NCT01467479 (8) [back to overview] | Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg) |
| NCT01467492 (8) [back to overview] | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT01467492 (8) [back to overview] | Percentage of Participants With Extended Rapid Viral Response (eRVR) |
| NCT01467492 (8) [back to overview] | Percentage of Participants With On Treatment Virologic Failure |
| NCT01467492 (8) [back to overview] | Percentage of Participants With Relapse |
| NCT01467492 (8) [back to overview] | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Actual Dose of Study Drug (SVR12) |
| NCT01467492 (8) [back to overview] | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Actual Dose of Study Drug (SVR24) |
| NCT01467492 (8) [back to overview] | Percentage of Participants With Virologic Breakthrough |
| NCT01467492 (8) [back to overview] | Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region |
| NCT01467505 (6) [back to overview] | Percentage of Participants With Extended Rapid Viral Response (eRVR) |
| NCT01467505 (6) [back to overview] | Percentage of Participants With Rapid Viral Response (RVR) |
| NCT01467505 (6) [back to overview] | Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) |
| NCT01467505 (6) [back to overview] | Percentage of Participants With On-Treatment Virologic Failure |
| NCT01467505 (6) [back to overview] | Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) |
| NCT01467505 (6) [back to overview] | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT01468337 (9) [back to overview] | Total Number of Ocular Adverse Events Related to Investigational Product |
| NCT01468337 (9) [back to overview] | Total Number of Severe Non-ocular Adverse Events Related to the Investigational Product |
| NCT01468337 (9) [back to overview] | Total Number of Severe Ocular Adverse Events Related to the Investigational Product |
| NCT01468337 (9) [back to overview] | Changes in Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week 48 Compared to Baseline |
| NCT01468337 (9) [back to overview] | Changes in Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week 2 Compared to Baseline |
| NCT01468337 (9) [back to overview] | Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 2 Compared to Baseline |
| NCT01468337 (9) [back to overview] | Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 48 Compared to Baseline |
| NCT01468337 (9) [back to overview] | Number of Participants Who Withdrew From the Study |
| NCT01468337 (9) [back to overview] | Total Number of Non-ocular Adverse Events Related to the Investigational Product |
| NCT01471574 (6) [back to overview] | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene |
| NCT01471574 (6) [back to overview] | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) |
| NCT01471574 (6) [back to overview] | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation |
| NCT01471574 (6) [back to overview] | Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) |
| NCT01471574 (6) [back to overview] | Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL |
| NCT01471574 (6) [back to overview] | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) |
| NCT01479868 (12) [back to overview] | Change From Baseline in CD4+ Cell Count in Percentage |
| NCT01479868 (12) [back to overview] | Mean Change From Baseline in CD4+ Cell Count |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Viral Relapse |
| NCT01479868 (12) [back to overview] | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load |
| NCT01479868 (12) [back to overview] | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24) |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Viral Breakthrough |
| NCT01479868 (12) [back to overview] | Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Normalized Alanine Aminotransferase Levels |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12) |
| NCT01479868 (12) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT01482767 (6) [back to overview] | CD4+ T-Cell Count (CD4) Change From Baseline |
| NCT01482767 (6) [back to overview] | Number of Participants With Undetectable HCV RNA at Week 4, 8 and 12 Study Visits |
| NCT01482767 (6) [back to overview] | Percentage of Participants With Sustained Virologic Response at 12 Weeks After Treatment Discontinuation (SVR12) |
| NCT01482767 (6) [back to overview] | Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) |
| NCT01482767 (6) [back to overview] | Percentage of Participants With HIV-1 Viral Load <50 Copies/mL |
| NCT01482767 (6) [back to overview] | Percentage of Participants With Sustained Virologic Response at 24 Weeks After Treatment Discontinuation (SVR24) |
| NCT01498068 (6) [back to overview] | Number of Participants With Virologic Failure |
| NCT01498068 (6) [back to overview] | Number of Participants With Extended Rapid Virologic Response (eRVR) |
| NCT01498068 (6) [back to overview] | Median Change in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) |
| NCT01498068 (6) [back to overview] | Number of Participants in Each Specific Category of Treatment Outcome |
| NCT01498068 (6) [back to overview] | Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48 |
| NCT01498068 (6) [back to overview] | Number of Participants With Rapid Virologic Response (RVR) at Week 4 |
| NCT01514370 (19) [back to overview] | Percentage of Relapse-Free Subjects at Month 12 and Month 24 |
| NCT01514370 (19) [back to overview] | Cumulative Number of New T1 (Hypointense) Lesions |
| NCT01514370 (19) [back to overview] | Number of Subjects With Clinical Significant Abnormality in Laboratory Parameters |
| NCT01514370 (19) [back to overview] | Number of Subjects With One Concomitant Medication From Baseline up to Month 24 |
| NCT01514370 (19) [back to overview] | Percentage of Subjects Treated With Glucocorticoids Due to Relapses During 24 Months |
| NCT01514370 (19) [back to overview] | Percentage of Subjects With Active (New/Enlarging) T2 Lesions at Month 24 |
| NCT01514370 (19) [back to overview] | Time on Treatment (Adherence to Treatment) |
| NCT01514370 (19) [back to overview] | Hazard Ratio for Time to First Documented Relapse |
| NCT01514370 (19) [back to overview] | Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation |
| NCT01514370 (19) [back to overview] | Percentage of Subjects Free From Expanded Disability Status Scale (EDSS) Progression at Month 12 and 24 |
| NCT01514370 (19) [back to overview] | Percentage of Subjects With Combined Unique Active (CUA) Lesions at Month 12 and 24 |
| NCT01514370 (19) [back to overview] | Annualized Relapse Rate at Month 12 and 24 |
| NCT01514370 (19) [back to overview] | Total Number of Reported Relapses at Month 3, 6, 12 and 24 |
| NCT01514370 (19) [back to overview] | Mean Number of New Gadolinium (Gd)-Enhancing Lesions at Month 12 and 24 |
| NCT01514370 (19) [back to overview] | Mean Number of New T1 (Hypointense) Lesions at Month 12 and 24 |
| NCT01514370 (19) [back to overview] | Number of Subjects With Premature Termination From Treatment |
| NCT01514370 (19) [back to overview] | Hazard Ratio for Time to First Sustained Expanded Disability Status Scale (EDSS) Progression |
| NCT01514370 (19) [back to overview] | Number of Subjects With Active (New or Enlarging) T2 Lesions Assessed by Magnetic Resonance Imaging (MRI) at Month 12 |
| NCT01514370 (19) [back to overview] | Flu-like Symptoms (FLS) Assessed by FLS Scale Score |
| NCT01524679 (2) [back to overview] | Change in Quantitative HBs Antigen at Week 12 |
| NCT01524679 (2) [back to overview] | Change in Quantitative HBs Antigen at Week 24 |
| NCT01525628 (24) [back to overview] | Cmax of Deleobuvir (BI 207127) |
| NCT01525628 (24) [back to overview] | Cmax of Caffeine |
| NCT01525628 (24) [back to overview] | Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) |
| NCT01525628 (24) [back to overview] | C6hr of Deleobuvir Reduction Metabolite CD 6168 |
| NCT01525628 (24) [back to overview] | C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) |
| NCT01525628 (24) [back to overview] | C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) |
| NCT01525628 (24) [back to overview] | C6hr of Deleobuvir (BI 207127) |
| NCT01525628 (24) [back to overview] | C24hr of Faldaprevir (BI 201335) |
| NCT01525628 (24) [back to overview] | AUC 0-infinity of Tolbutamide |
| NCT01525628 (24) [back to overview] | AUC 0-infinity of Midazolam |
| NCT01525628 (24) [back to overview] | AUC 0-infinity of Caffeine |
| NCT01525628 (24) [back to overview] | AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) |
| NCT01525628 (24) [back to overview] | AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 |
| NCT01525628 (24) [back to overview] | AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) |
| NCT01525628 (24) [back to overview] | AUC 0-6hr of Deleobuvir (BI 207127) |
| NCT01525628 (24) [back to overview] | Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours |
| NCT01525628 (24) [back to overview] | Number of Participants With Sustained Virological Response (SVR12) |
| NCT01525628 (24) [back to overview] | Cmax of Faldaprevir (BI 201335) |
| NCT01525628 (24) [back to overview] | Cmax of Tolbutamide |
| NCT01525628 (24) [back to overview] | Cmax of Midazolam |
| NCT01525628 (24) [back to overview] | AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) |
| NCT01525628 (24) [back to overview] | Cmax of Deleobuvir Reduction Metabolite CD 6168 |
| NCT01525628 (24) [back to overview] | Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) |
| NCT01525628 (24) [back to overview] | Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) |
| NCT01534182 (5) [back to overview] | Change in Patient-reported Depression |
| NCT01534182 (5) [back to overview] | Change in Patient-reported Treatment Satisfaction |
| NCT01534182 (5) [back to overview] | Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute) |
| NCT01534182 (5) [back to overview] | Changes in Patient-reported Effectiveness, Side Effects and Convenience |
| NCT01534182 (5) [back to overview] | Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death |
| NCT01544920 (2) [back to overview] | Percentage of Participants Who Had Undetectable HCV RNA at Week 4 Achieving SVR24 |
| NCT01544920 (2) [back to overview] | Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) 24 Weeks After Completing Study Treatment (SVR24) |
| NCT01545141 (1) [back to overview] | Treatment Related Adverse Events |
| NCT01609010 (10) [back to overview] | Overall Survival |
| NCT01609010 (10) [back to overview] | Overall Survival (OS) - Percentage of Participants With an Event |
| NCT01609010 (10) [back to overview] | Time to Disease Progression |
| NCT01609010 (10) [back to overview] | Treatment Failure - Percentage of Participants With an Event |
| NCT01609010 (10) [back to overview] | Treatment Failure - Time to Event |
| NCT01609010 (10) [back to overview] | Duration of Response |
| NCT01609010 (10) [back to overview] | Duration of Response - Percentage of Participants With an Event |
| NCT01609010 (10) [back to overview] | Percentage of Participants Achieving CR or CRu |
| NCT01609010 (10) [back to overview] | Percentage of Participants Achieving Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) |
| NCT01609010 (10) [back to overview] | Disease Progression - Percentage of Participants With an Event |
| NCT01609933 (4) [back to overview] | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Treatment (SVR12) |
| NCT01609933 (4) [back to overview] | Percentage of Participants Achieving Virologic Response 24 Weeks Post Treatment (SVR24) |
| NCT01609933 (4) [back to overview] | Percentage of Participants With Extended Rapid Virologic Response (eRVR) |
| NCT01609933 (4) [back to overview] | Number of Participants With Adverse Events |
| NCT01641120 (4) [back to overview] | Change in Patient Visual Analog Scale Score for Pre-injection Anxiety |
| NCT01641120 (4) [back to overview] | Fear of Injection |
| NCT01641120 (4) [back to overview] | Perception of Needle |
| NCT01641120 (4) [back to overview] | Visual Analog Scale Score for Post-injection Pain |
| NCT01641926 (5) [back to overview] | Percentage of HBeAg(-) Participants Achieving Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels <2000 IU/mL at 24 Weeks Post-treatment |
| NCT01641926 (5) [back to overview] | Percentage of HBeAg(+) and HBeAg(-) Participants Achieving Alanine Aminotransferase (ALT) Normalization at 24 Weeks Post-treatment |
| NCT01641926 (5) [back to overview] | Percentage of HBeAg(+) Participants Achieving HBeAg Seroconversion at 24 Weeks Post-treatment |
| NCT01641926 (5) [back to overview] | Percentage of HBeAg(+) Participants Achieving HBV DNA <2000 IU/mL at 24 Weeks Post-treatment |
| NCT01641926 (5) [back to overview] | Percentage of HBeAg(+) Participants Achieving the Combined Response of HBeAg Seroconversion and HBV DNA <2000 IU/mL at 24 Weeks Post-treatment |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval and QT Interval Corrected Bazett's Formula (QTcB), QT Interval Corrected Using Fridericia's Formula (QTcF) Values at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Red Blood Cell Count at the Indicated Time Points After Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Red Blood Cell Count at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Total Bilirubin and Creatinine at the Indicated Time Points After Week 12 |
| NCT01648140 (35) [back to overview] | Mean GSK2336805 Plasma Concentrations on Day 1, Day 2, Week 4, and Week 12 |
| NCT01648140 (35) [back to overview] | Number of Participants Achieving Very Rapid Virologic Response (vRVR), Rapid Virologic Response (RVR), Complete Early Virologic Response (cEVR), Sustained Virologic Response 12 and 24 (SVR12 and SVR24) With Response Guided Treatment (RGT) |
| NCT01648140 (35) [back to overview] | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) up to Week 12 |
| NCT01648140 (35) [back to overview] | Number of Participants With Any AEs and Any SAEs After Week 12 |
| NCT01648140 (35) [back to overview] | Number of Participants With Shift From Baseline in Urinalysis Data up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in ALP, ALT, AST, CK and GGT at the Indicated Time Points After Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Chloride, Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Chloride, Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus and Urea/BUN at the Indicated Time Points After Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Creatinine Clearance at the Indicated Time Points After Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Direct Bilirubin, Total Bilirubin and Creatinine at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Electrocardiographic (ECG) Heart Rate Values at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Heart Rate at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Hematocrit at the Indicated Time Points After Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Hematocrit at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Hemoglobin at the Indicated Time Points After Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Creatinine Clearance at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points After Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count at the Indicated Time Points After Week 12 |
| NCT01648140 (35) [back to overview] | Apparent Clearance (CL/F) at Week 4 |
| NCT01648140 (35) [back to overview] | Apparent Volume of Distribution (Vz/F) at Week 4 |
| NCT01648140 (35) [back to overview] | Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) at Week 4 |
| NCT01648140 (35) [back to overview] | Number of Participants Achieving eRVR |
| NCT01648140 (35) [back to overview] | Time of Maximal Plasma Concentration (Tmax) of GSK2336805 at Week 4 |
| NCT01648140 (35) [back to overview] | Maximum Plasma Concentration (Cmax) and Concentration at the End of the Dosing Interval (Ctau) of GSK2336805 at Week 4 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Albumin at the Indicated Time Points After Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Albumin at the Indicated Time Points up to Week 12 |
| NCT01648140 (35) [back to overview] | Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase (CK) and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points up to Week 12 |
| NCT01659567 (14) [back to overview] | OR for Impact of Duration of Treatment After Achieving RVR on SVR |
| NCT01659567 (14) [back to overview] | OR for Impact of Duration of Treatment After Achieving cEVR on SVR |
| NCT01659567 (14) [back to overview] | OR for Impact of Cumulative Doses of Pegylated Interferon Alfa-2a on SVR |
| NCT01659567 (14) [back to overview] | OR for Impact of Body Weight on SVR |
| NCT01659567 (14) [back to overview] | OR for Impact of Baseline Viral Load Count on SVR |
| NCT01659567 (14) [back to overview] | OR for Impact of Baseline Level of Fibrosis (kPa) on SVR |
| NCT01659567 (14) [back to overview] | OR for Impact of Baseline Alanine Transaminase (ALT) Level on SVR |
| NCT01659567 (14) [back to overview] | Odds Ratio (OR) for Impact of Age on SVR |
| NCT01659567 (14) [back to overview] | OR for Impact of Cumulative Doses of Ribavirin on SVR |
| NCT01659567 (14) [back to overview] | PPV of Complete Early Viral Response (cEVR) on SVR |
| NCT01659567 (14) [back to overview] | Positive Predictive Value (PPV) of Rapid Viral Response (RVR) on SVR |
| NCT01659567 (14) [back to overview] | Percentage of Participants Achieving Sustained Virological Response (SVR) |
| NCT01659567 (14) [back to overview] | OR for Impact of Overall Duration of Treatment on SVR |
| NCT01659567 (14) [back to overview] | OR for Impact of Gender on SVR |
| NCT01706575 (6) [back to overview] | Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96 |
| NCT01706575 (6) [back to overview] | Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48 |
| NCT01706575 (6) [back to overview] | Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48) |
| NCT01706575 (6) [back to overview] | Safety: Percentage of Participants With Adverse Events (AE) |
| NCT01706575 (6) [back to overview] | Efficacy: Number of Participants With Serum HBsAg Loss at Week 12 That Persisted up to Week 96 |
| NCT01706575 (6) [back to overview] | Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease >/= 50% From Baseline at End of the Combination Treatment (Week 48) |
| NCT01708941 (4) [back to overview] | Overall Survival |
| NCT01708941 (4) [back to overview] | Overall Survival (OS) |
| NCT01708941 (4) [back to overview] | Progression-free Survival |
| NCT01708941 (4) [back to overview] | Progression-free Survival (PFS) |
| NCT01710501 (8) [back to overview] | Percentage of Participants Achieving Undetectable HCV RNA During Treatment by Time Point |
| NCT01710501 (8) [back to overview] | Percentage of Participants Achieving SVR4 |
| NCT01710501 (8) [back to overview] | Number of Participants Developing Post-baseline Antiviral Resistance to Grazoprevir Among Participants Not Achieving SVR24 Response |
| NCT01710501 (8) [back to overview] | Number of Participants Discontinued From Study Treatment Due to AEs During the Treatment Period and First 14 Follow-up Days |
| NCT01710501 (8) [back to overview] | Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12) |
| NCT01710501 (8) [back to overview] | Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment by Time Point |
| NCT01710501 (8) [back to overview] | Number of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days |
| NCT01710501 (8) [back to overview] | Percentage of Subjects Achieving SVR24 |
| NCT01741545 (9) [back to overview] | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death |
| NCT01741545 (9) [back to overview] | Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment |
| NCT01741545 (9) [back to overview] | Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-Up Week 12 |
| NCT01741545 (9) [back to overview] | Percentage of Participants With Complete Early Virologic Response (cEVR) |
| NCT01741545 (9) [back to overview] | Percentage of Participants With End of the Treatment Response (EOTR) |
| NCT01741545 (9) [back to overview] | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities |
| NCT01741545 (9) [back to overview] | Percentage of Participants With Rapid Virologic Response (RVR) |
| NCT01741545 (9) [back to overview] | Percentage of Participants With Treatment-Emergent Cytopenic Abnormalities On-Treatment |
| NCT01741545 (9) [back to overview] | Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24) |
| NCT01766024 (3) [back to overview] | Cmax of Interferon Beta-1a |
| NCT01766024 (3) [back to overview] | AUC(0-168) and AUC(0-∞) of Neopterin and MxA Protein |
| NCT01766024 (3) [back to overview] | Area Under Concentration-time Curve (AUC) of Interferon (IFN) Beta-1a From the Moment of Drug Administration Until 48 Hours and to Infinity(AUC(0-48) and AUC(0-∞) Respectively) |
| NCT01770483 (2) [back to overview] | Normalization of Alanine Transferase Test |
| NCT01770483 (2) [back to overview] | Sustained Viral Response, |
| NCT01854528 (6) [back to overview] | Percentage of Participants With Virologic Failure During Treatment |
| NCT01854528 (6) [back to overview] | Percentage of Participants With Virologic Relapse After Treatment |
| NCT01854528 (6) [back to overview] | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment |
| NCT01854528 (6) [back to overview] | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment |
| NCT01854528 (6) [back to overview] | Mean Change From Baseline to Final Treatment Visit in the Mental Component Summary (MCS) Score of the Short-Form 36 Health Survey - Version 2 (SF-36v2) |
| NCT01854528 (6) [back to overview] | Mean Change From Baseline to Final Treatment Visit in the Physical Component Summary (PCS) Score of the Short-Form 36 Health Survey - Version 2 (SF-36v2) |
| NCT01854697 (7) [back to overview] | Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS) |
| NCT01854697 (7) [back to overview] | Percentage of Participants With Virologic Failure During Treatment |
| NCT01854697 (7) [back to overview] | Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS) |
| NCT01854697 (7) [back to overview] | Percentage of Participants With Post-treatment Relapse |
| NCT01854697 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses |
| NCT01854697 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) |
| NCT01854697 (7) [back to overview] | Percentage of Participants With SVR12 - Secondary Efficacy Analyses |
| NCT01864148 (4) [back to overview] | Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs |
| NCT01864148 (4) [back to overview] | Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 |
| NCT01864148 (4) [back to overview] | Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint |
| NCT01864148 (4) [back to overview] | Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint |
| NCT01866930 (12) [back to overview] | Number of Participants With Treatment-emergent Grade 3/4 Lab Abnormalities |
| NCT01866930 (12) [back to overview] | Number of Participants With Rapid Virologic Response (RVR) and Extended Rapid Virologic Response (eRVR) |
| NCT01866930 (12) [back to overview] | Number of Participants With On-treatment IFN-associated Flu-like or Musculoskeletal Symptoms |
| NCT01866930 (12) [back to overview] | Number of Participants Who Died or Experienced Severe Adverse Events (SAEs), Dose Reductions of Lambda or Discontinuation Due to Adverse Events (AEs) |
| NCT01866930 (12) [back to overview] | Number of Participants With Treatment Emergent Cytopenic Abnormalities |
| NCT01866930 (12) [back to overview] | Number of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) |
| NCT01866930 (12) [back to overview] | Mean Percent Change in Total Lymphocyte Count From Baseline to End of Treatment |
| NCT01866930 (12) [back to overview] | Mean Percent Change in Absolute CD4 T Lymphocyte Count From Baseline to End of Treatment |
| NCT01866930 (12) [back to overview] | Mean Change in Total Lymphocyte Count From Baseline to End of Treatment |
| NCT01866930 (12) [back to overview] | Mean Percent Change in Platelet Count From Baseline to End of Treatment |
| NCT01866930 (12) [back to overview] | Mean Change in Absolute CD4 T Lymphocyte Count From Baseline to End of Treatment |
| NCT01866930 (12) [back to overview] | Mean Change in Platelet Count From Baseline to End of Treatment |
| NCT01892722 (1) [back to overview] | Frequency of Relapses in Patients Treated for up to 24 Months |
| NCT01925183 (2) [back to overview] | Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT01925183 (2) [back to overview] | Proportion of Subjects With Sustained Virologic Response (SVR12) |
| NCT01935089 (1) [back to overview] | Change From Baseline in Copies of HIV DNA Per CD4+ T Cell at Week 24 |
| NCT01939002 (31) [back to overview] | Summary of Average Duration of FLS in the First 8 Weeks of Treatment |
| NCT01939002 (31) [back to overview] | Percentage of Participants With Any FLS in the 4-Week Run-In Period, During the First 8 Weeks of Treatment, and During 48 Weeks of Treatment |
| NCT01939002 (31) [back to overview] | Summary of Average Duration of FLS in the 48 Weeks of Treatment |
| NCT01939002 (31) [back to overview] | Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Effectiveness Scale Factor: Between FLS Management Arms |
| NCT01939002 (31) [back to overview] | Summary of FLS-Visual Analogue Scale (VAS) During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment |
| NCT01939002 (31) [back to overview] | Summary of FLS-VAS During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment |
| NCT01939002 (31) [back to overview] | Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Global Satisfaction Scale Factor: Between FLS Management Arms |
| NCT01939002 (31) [back to overview] | Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS |
| NCT01939002 (31) [back to overview] | Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Side Effects Scale Factor: Between FLS Management Arms |
| NCT01939002 (31) [back to overview] | Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs |
| NCT01939002 (31) [back to overview] | Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to the First 8 Weeks |
| NCT01939002 (31) [back to overview] | Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Symptoms: Overall Population |
| NCT01939002 (31) [back to overview] | Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Treatment: Overall Population |
| NCT01939002 (31) [back to overview] | Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Usual Work Days Per Week: Overall Population |
| NCT01939002 (31) [back to overview] | Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population |
| NCT01939002 (31) [back to overview] | Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment |
| NCT01939002 (31) [back to overview] | Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population |
| NCT01939002 (31) [back to overview] | Change From Baseline Visit (Day 1) to Week 48 in Walking Disability Status as Measured by Patient Determined Disease Steps (PDDS): Overall Population |
| NCT01939002 (31) [back to overview] | Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing |
| NCT01939002 (31) [back to overview] | Antibody Data in the Overall Population: IFN β-1a Antibody Screening |
| NCT01939002 (31) [back to overview] | Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing |
| NCT01939002 (31) [back to overview] | Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Overall Population |
| NCT01939002 (31) [back to overview] | Summary of Average Duration of FLS Within the Last 4 Weeks of the BIIB017 Treatment Period Compared With the Duration of FLS in the 4-Week Run-In Period |
| NCT01939002 (31) [back to overview] | Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to 48 Weeks |
| NCT01939002 (31) [back to overview] | Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Between FLS Management Arms |
| NCT01939002 (31) [back to overview] | Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Convenience Scale Factor: Between FLS Management Arms |
| NCT01939002 (31) [back to overview] | Summary of Severity of FLS (Per FLS-S) in the First 8 Weeks Compared to 4-Week Run-In Period Between Arms |
| NCT01939002 (31) [back to overview] | Summary of Severity of FLS (Per FLS-S) in the 48 Weeks of Treatment Compared to 4-Week Run-In Period Between Arms |
| NCT01939002 (31) [back to overview] | Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment |
| NCT01939002 (31) [back to overview] | Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population |
| NCT01939002 (31) [back to overview] | Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population |
| NCT01945294 (8) [back to overview] | Percentage of Participants With Undetectable HCV RNA Who Achieve Sustained Viral Response at Follow-up Week 12 (SVR12) [16-Week Arm vs. 28-Week Arm] |
| NCT01945294 (8) [back to overview] | Percentage of Participants With Treatment-Related Serious AEs (SAEs) |
| NCT01945294 (8) [back to overview] | Percentage of Participants With Relapse |
| NCT01945294 (8) [back to overview] | Percentage of Participants With Neutropenia |
| NCT01945294 (8) [back to overview] | Percentage of Participants With Anemia |
| NCT01945294 (8) [back to overview] | Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment |
| NCT01945294 (8) [back to overview] | Percentage of Participants With Undetectable HCV RNA Across Treatment |
| NCT01945294 (8) [back to overview] | Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs) |
| NCT01957709 (3) [back to overview] | Change in Class I Major Histocompatibility Complex (MHC) Expression After Treatment With IFN Gamma |
| NCT01957709 (3) [back to overview] | MHC Class II Expression |
| NCT01957709 (3) [back to overview] | Changes in Immune Response |
| NCT01965327 (2) [back to overview] | Change in Whole Blood Frataxin Levels |
| NCT01965327 (2) [back to overview] | Change in Total Friedreich Ataxia Rating Scale (FARS) Score |
| NCT02047734 (12) [back to overview] | Percent Change From Baseline in Normalized Brain Volume to Month 24 Based on Rank ANCOVA |
| NCT02047734 (12) [back to overview] | Percent Change From Baseline in Normalized Brain Volume to Month 24 |
| NCT02047734 (12) [back to overview] | Change From Baseline to Month 24 in Multiple Sclerosis Functional Composite (MSFC) Score Including the Low-Contrast Letter Acuity (LCLA) Test |
| NCT02047734 (12) [back to overview] | Adjusted Mean Number of New or Enlarging Hyperintense T2-Weighted Brain Magnetic Resonance Imaging (MRI) Lesions Per Scan Over 24 Months |
| NCT02047734 (12) [back to overview] | Adjusted Mean Number of Gadolinium Enhancing Brain Lesions at Month 24 |
| NCT02047734 (12) [back to overview] | Number of Participants With Treatment Emergent Adverse Events |
| NCT02047734 (12) [back to overview] | Mean Change From Baseline in Multiple Sclerosis Quality of Life (MSQOL)-54 Physical Health Composite Summary and Mental Health Composite Summary Scores |
| NCT02047734 (12) [back to overview] | Time to Onset of Disability Progression Confirmed After 6 Months |
| NCT02047734 (12) [back to overview] | Time to Onset of Disability Progression Confirmed After 3 Months |
| NCT02047734 (12) [back to overview] | Percentage of Participants Who Were New or Enlarging T2 Lesion-Free at Month 24 |
| NCT02047734 (12) [back to overview] | Percentage of Participants Who Were Gadolinium Enhancing (GdE) Lesion-Free at Month 24 |
| NCT02047734 (12) [back to overview] | Adjusted Annualized Relapse Rate (ARR) at the End of Month 24 |
| NCT02097849 (16) [back to overview] | Number of Participants With Shifts From Baseline in Hematology |
| NCT02097849 (16) [back to overview] | Number of Participants With Shifts From Baseline in Blood Chemistry |
| NCT02097849 (16) [back to overview] | Number of Participants With Abnormalities in Vital Signs |
| NCT02097849 (16) [back to overview] | Ratio of Serum Tetanus Level at Day 28 to Prevaccination |
| NCT02097849 (16) [back to overview] | Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs |
| NCT02097849 (16) [back to overview] | Ratio of Serum Pneumococcal Antibodies (Serotype 3) Level at Day 28 to Prevaccination |
| NCT02097849 (16) [back to overview] | Percentage of Pneumococcal Serotype 8 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level |
| NCT02097849 (16) [back to overview] | Percentage of Pneumococcal Serotype 8 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level |
| NCT02097849 (16) [back to overview] | Percentage of Tetanus Responders (≥ 2-Fold Rise) at Day 28 Compared to Prevaccination Level |
| NCT02097849 (16) [back to overview] | Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level |
| NCT02097849 (16) [back to overview] | Percentage of Meningococcal Serogroup C Responders (≥ 4-Fold Rise) Compared to Prevaccination Level |
| NCT02097849 (16) [back to overview] | Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level |
| NCT02097849 (16) [back to overview] | Percentage of Meningococcal Serogroup C Responders (≥ 2-Fold Rise) Compared to Prevaccination Level |
| NCT02097849 (16) [back to overview] | Percentage of Pneumococcal Serotype 3 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level |
| NCT02097849 (16) [back to overview] | Ratio of Serum Meningococcal Antibodies (Serogroup C) Level at Day 28 to Prevaccination |
| NCT02097849 (16) [back to overview] | Ratio of Serum Pneumococcal Antibodies (Serotype 8) Level at Day 28 to Prevaccination |
| NCT02106156 (9) [back to overview] | Percentage of Participants With Sustained Virologic Response (SVR) |
| NCT02106156 (9) [back to overview] | Duration of Peginterferon Alfa-2a Therapy |
| NCT02106156 (9) [back to overview] | Percentage Cumulative Dose of Peginterferon Alfa-2a Received |
| NCT02106156 (9) [back to overview] | Percentage Cumulative Dose of Ribavirin Received |
| NCT02106156 (9) [back to overview] | Percentage of Participants With Early Virologic Response (EVR) |
| NCT02106156 (9) [back to overview] | Percentage of Participants With End of Treatment (EOT) Response |
| NCT02106156 (9) [back to overview] | Percentage of Participants With Rapid Virologic Response (RVR) |
| NCT02106156 (9) [back to overview] | Percentage of Participants With Serious Adverse Drug Reactions (SADR) |
| NCT02106156 (9) [back to overview] | Percentage of Participants With the Most Frequent Concomitant Medications |
| NCT02118597 (7) [back to overview] | Percentage of Participants With Virological Response |
| NCT02118597 (7) [back to overview] | Number of Participants With Treatment Discontinuation |
| NCT02118597 (7) [back to overview] | Number of Participants With Virological Relapse |
| NCT02118597 (7) [back to overview] | Number of Participants With Virological Breakthrough |
| NCT02118597 (7) [back to overview] | Number of Participants With Treatment Discontinuation Due to Futility |
| NCT02118597 (7) [back to overview] | Number of Participants With Adverse Events |
| NCT02118597 (7) [back to overview] | Sustained Virological Response 24 (SVR24) Rate |
| NCT02151448 (11) [back to overview] | Time to Progression (TTP) |
| NCT02151448 (11) [back to overview] | Adverse Events Possibly, Probably or Definitely Related to Study Treatment |
| NCT02151448 (11) [back to overview] | CXCL10 (Interferon Gamma-induced Protein 10) Levels |
| NCT02151448 (11) [back to overview] | CXCL11 (C-X-C Motif Chemokine 11) Levels |
| NCT02151448 (11) [back to overview] | Interleukin 10 (IL-10) Levels |
| NCT02151448 (11) [back to overview] | Interleukin 6 (IL-6) Cytokine Levels |
| NCT02151448 (11) [back to overview] | Interleukin-8 (IL-8) Cytokine Levels |
| NCT02151448 (11) [back to overview] | Overall Survival (OS) |
| NCT02151448 (11) [back to overview] | Progression-free Survival (PFS) |
| NCT02151448 (11) [back to overview] | Stromal Derived Factor 1 Alpha (SDF-1A/CXCL-12) Chemokine Levels |
| NCT02151448 (11) [back to overview] | Tumor Necrosis Factor (TFNα) Cytokine Levels |
| NCT02155322 (2) [back to overview] | Percentage of Participants Experiencing Adverse Events (AEs) |
| NCT02155322 (2) [back to overview] | Percentage of Participants Discontinuing Study Drug Because of AEs |
| NCT02159482 (2) [back to overview] | Proportion of Clinical Responders (Complete Response + Partial Response) |
| NCT02159482 (2) [back to overview] | Proportion of Patients Experiencing an Increase in the Magnitude of the Tumor Antigen-specific Immune Response |
| NCT02168361 (2) [back to overview] | Serum HCV RNA Level |
| NCT02168361 (2) [back to overview] | Proportion of Participants With Sustained Virologic Response 12 (SVR-12) |
| NCT02218164 (4) [back to overview] | Occurence of Treatment Related Serious Adverse Events (SAEs) |
| NCT02218164 (4) [back to overview] | Overall Survival (OS) |
| NCT02218164 (4) [back to overview] | Objective Response Rate (ORR) |
| NCT02218164 (4) [back to overview] | Progression Free Survival (PFS) |
| NCT02247440 (7) [back to overview] | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% |
| NCT02247440 (7) [back to overview] | Number of Participants With at Least a Serious Adverse Events Associated With Study Treatment (Peg-interferon and Ribavirin) |
| NCT02247440 (7) [back to overview] | Number of Participants With Sustained Virological Response 6 Months After Treatment Discontinuation |
| NCT02247440 (7) [back to overview] | Number of Adverse Events by Severity Grade |
| NCT02247440 (7) [back to overview] | Number of Participants Grouped by HIV-1 RNA Concentrations |
| NCT02247440 (7) [back to overview] | Number of Participants Able to Perform Self-injections of Peg-interferon |
| NCT02247440 (7) [back to overview] | Number of Participants Completed the First 24 and 48 Weeks of Treatment |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Subjects Who Missed Any Partial Days From Work Due to Multiple Sclerosis (MS). |
| NCT02254304 (29) [back to overview] | Number of Subjects With Medication Adherence Based on Morisky Medication Adherence Score |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Full Days Missed From Work by Subjects |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Days Per Week Assistant Worked For Subject Due to Multiple Sclerosis (MS) |
| NCT02254304 (29) [back to overview] | Number of Subjects With Reasons of Missed Injections |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Times Subjects Visited Emergency Room Due to Multiple Sclerosis (MS) |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Visits to Clinic by Subjects Due to Multiple Sclerosis (MS) |
| NCT02254304 (29) [back to overview] | Percentage of Subjects With Treatment Adherence |
| NCT02254304 (29) [back to overview] | Percentage of Subjects With Relapse by Adherence Category |
| NCT02254304 (29) [back to overview] | Percentage of Subjects With Relapse by Adherence Category |
| NCT02254304 (29) [back to overview] | Percentage of Subjects Who Prematurely Terminated Treatment and Reasons |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Visits by Healthcare Professional to Subjects' Home |
| NCT02254304 (29) [back to overview] | Overall Evaluation of RebiSmart Use as Assessed by Investigator |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Working Days Missed by Relative or Friend Due to Subjects' Multiple Sclerosis (MS) |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Subjects Whose Relatives or Friends Missed Work Due to Subjects' Multiple Sclerosis (MS) |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire -Number of Subjects Who Paid Someone to Assist Them Due to Multiple Sclerosis (MS) |
| NCT02254304 (29) [back to overview] | Mean Number of Relapses in RMS Subjects |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Days Subjects Hospitalized Due to Multiple Sclerosis (MS) |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Subjects Accomplished Less Work Due to Multiple Sclerosis (MS) |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Hours Per Day Missed From Work by Subjects |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Subjects Who Missed Any Full Days From Work Due to Multiple Sclerosis (MS). |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Hours Per Day Assistant Worked for Subject Due to Multiple Sclerosis (MS) |
| NCT02254304 (29) [back to overview] | Percentage of Relapse-free RMS Subjects |
| NCT02254304 (29) [back to overview] | Time to the First Relapse for CIS Subjects |
| NCT02254304 (29) [back to overview] | Body Mass Index (BMI) |
| NCT02254304 (29) [back to overview] | Expanded Disability Status Scale (EDSS) Score |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Subjects Visiting Different Types of Doctors During Their Clinical Visit |
| NCT02254304 (29) [back to overview] | Healthcare Resource Utilization Questionnaire - Number of Subjects With Percentage of Work Completed Despite of Multiple Sclerosis (MS) |
| NCT02254304 (29) [back to overview] | Number of Subjects With Adverse Event or Adverse Drug Reaction (AE/ADR), Serious AE/ADR, AE/ADR Leading to Death and AE/ADR Leading to Early Termination |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Loss of HBsAg |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg) |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) |
| NCT02263079 (19) [back to overview] | Change From Baseline in HBV DNA Levels in the Untreated Control Participants |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Adverse Events (AEs) |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg) |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs |
| NCT02263079 (19) [back to overview] | Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs |
| NCT02263079 (19) [back to overview] | Serum Concentration of Peg-INF-Alfa-2A |
| NCT02263079 (19) [back to overview] | Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm |
| NCT02263079 (19) [back to overview] | Percentage of Participants With AEs Leading to Dose Modification or Interruption |
| NCT02294058 (11) [back to overview] | Change From Baseline to Month 12 in Multiple Sclerosis Functional Composite (MSFC) Score Including the Low-Contrast Letter Acuity (LCLA) Test |
| NCT02294058 (11) [back to overview] | Adjusted Mean Number of New or Enlarging Hyperintense T2-Weighted Brain Magnetic Resonance Imaging (MRI) Lesions Per Scan Over 12 Months |
| NCT02294058 (11) [back to overview] | Adjusted Mean Number of Gadolinium Enhancing (GdE) Brain MRI Lesions at Month 12 |
| NCT02294058 (11) [back to overview] | Adjusted Annualized Relapse Rate (ARR) During the Treatment Period |
| NCT02294058 (11) [back to overview] | Percent Change From Baseline in Normalized Brain Volume at Month 12 |
| NCT02294058 (11) [back to overview] | Number of Participants With Treatment Emergent Adverse Events |
| NCT02294058 (11) [back to overview] | Mean Change From Baseline in Multiple Sclerosis Quality of Life (MSQOL)-54 Physical Health Composite Summary and Mental Health Composite Summary Scores |
| NCT02294058 (11) [back to overview] | Time to Onset of Disability Progression Confirmed After 6 Months |
| NCT02294058 (11) [back to overview] | Time to Onset of Disability Progression Confirmed After 3 Months |
| NCT02294058 (11) [back to overview] | Percentage of Participants Who Were T2 Lesion-Free at Month 12 |
| NCT02294058 (11) [back to overview] | Percentage of Participants Who Were Gadolinium Enhancing Lesion-Free at Month 12 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 5 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 52 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 8 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Day 1 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Day 2 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Day 3 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 2 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 5 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 52 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 52 |
| NCT02338973 (32) [back to overview] | Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Day 2 |
| NCT02338973 (32) [back to overview] | Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 2 |
| NCT02338973 (32) [back to overview] | Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Day 3 |
| NCT02338973 (32) [back to overview] | Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 5 |
| NCT02338973 (32) [back to overview] | Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 52 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Day 3 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Day 2 |
| NCT02338973 (32) [back to overview] | Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 8 |
| NCT02338973 (32) [back to overview] | Number and Severity of IP-related AEs |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Day 1 |
| NCT02338973 (32) [back to overview] | Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 8 |
| NCT02338973 (32) [back to overview] | Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 52 |
| NCT02338973 (32) [back to overview] | Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 5 |
| NCT02338973 (32) [back to overview] | Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 2 |
| NCT02338973 (32) [back to overview] | Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Day 3 |
| NCT02338973 (32) [back to overview] | Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Day 2 |
| NCT02338973 (32) [back to overview] | Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Day 1 |
| NCT02338973 (32) [back to overview] | Number of Participants Who Withdrew |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 2 |
| NCT02338973 (32) [back to overview] | Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 8 |
| NCT02338973 (32) [back to overview] | Change in Central Visual Field Sensitivity at Day 2 and Week 5 Compared to Baseline. |
| NCT02338973 (32) [back to overview] | Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Day 1 |
| NCT02340962 (8) [back to overview] | Change From Baseline in HCV RNA (log10 IU/mL) |
| NCT02340962 (8) [back to overview] | Proportion of Subjects Achieving Sustained Viral Response at 4, 8, and 24 Weeks After the End of Treatment (SVR4, SVR8, and SVR24) |
| NCT02340962 (8) [back to overview] | Proportion of Subjects Experiencing Virologic Failure During Treatment and Viral Relapse After the End of Treatment. |
| NCT02340962 (8) [back to overview] | Proportion of Subjects With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal Limit of ALT at Final Treatment Visit. |
| NCT02340962 (8) [back to overview] | Proportion of Subjects Achieving Sustained Viral Response at 12 Weeks After the End of Treatment. |
| NCT02340962 (8) [back to overview] | Mean Absolute Values in HCV RNA (log10 IU/mL) |
| NCT02340962 (8) [back to overview] | Proportion of Subjects Achieving HCV RNA < LLOQ, TND |
| NCT02340962 (8) [back to overview] | Proportion of Subjects Achieving HCV RNA < Lower Limit of Quantification, Target Detected or Target Not Detected (< LLOQ, TD or TND) |
| NCT02343224 (3) [back to overview] | Number of Children Responding to Treatment |
| NCT02343224 (3) [back to overview] | Number of Participants Meeting Event Free Survival Criteria |
| NCT02343224 (3) [back to overview] | Number of Participants Meeting Overall Survival Criteria |
| NCT02359877 (6) [back to overview] | Adverse Event (AE) and Serious Adverse Event (SAE) Incidence |
| NCT02359877 (6) [back to overview] | AUC (0-168); AUC (0-336); AUC (0-672); AUC (0-∞ ) of Interferon (IFN) Beta-1a |
| NCT02359877 (6) [back to overview] | Adverse Event (AE) and Serious Adverse Event (SAE) Incidence BCD-054 - 180 mcg - SC/IM |
| NCT02359877 (6) [back to overview] | AUC(0-last); AUC (0-∞ ) BCD-054 of Interferon (IFN) Beta-1a - 180 mcg - SC, BCD-054 - 180 mcg - IM |
| NCT02359877 (6) [back to overview] | AUC(0-∞), AUC(0-last) of Neopterin |
| NCT02359877 (6) [back to overview] | AUC (0-168); AUC (0-336); AUC (0-672);AUC (0-∞ ) of Neopterin |
| NCT02415127 (4) [back to overview] | Change From Baseline to Week 26 in Total Friedreich Ataxia Rating Scale Score (FARStot) |
| NCT02415127 (4) [back to overview] | Change From Baseline to Week 26 in the Friedreich's Ataxia Rating Scale (FARS)-mNeuro Score |
| NCT02415127 (4) [back to overview] | Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score |
| NCT02415127 (4) [back to overview] | Change From Baseline at Week 26 in Timed 25-Foot Walk (T25FW) |
| NCT02430181 (1) [back to overview] | Improvement in Quantitative Serum HDV RNA Levels After 4-12 Weeks of Lonafarnib-based Therapy |
| NCT02430194 (4) [back to overview] | ALT Normalization at End of Treatment |
| NCT02430194 (4) [back to overview] | < LLOQ in HDV RNA at End of Treatment (EOT) |
| NCT02430194 (4) [back to overview] | ≥2 log10 Decline of HDV RNA From Baseline at End of Treatment (EOT) |
| NCT02430194 (4) [back to overview] | Mean HDV RNA Decline |
| NCT02491684 (15) [back to overview] | AUC for Change in the Evening PEF From Baseline to up to 30 Days |
| NCT02491684 (15) [back to overview] | Proportion of Patients With Severe Asthma Exacerbations Within 7 and 30 Days Following Randomisation |
| NCT02491684 (15) [back to overview] | Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation |
| NCT02491684 (15) [back to overview] | AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days |
| NCT02491684 (15) [back to overview] | AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days |
| NCT02491684 (15) [back to overview] | Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) |
| NCT02491684 (15) [back to overview] | Change in Health-related Quality of Life as Measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) From Baseline up to 30 Days |
| NCT02491684 (15) [back to overview] | Change in the Proportion of Night-time Awakening Using the ePRO Questionnaire From Baseline up to 30 Days |
| NCT02491684 (15) [back to overview] | AUC for Change in Daytime and Night-time Reliever Medication Use From Baseline up to 14 Days |
| NCT02491684 (15) [back to overview] | Duration of Moderate or Severe Exacerbations |
| NCT02491684 (15) [back to overview] | AUC for Change in the Evening FEV1 From Baseline up to 30 Days |
| NCT02491684 (15) [back to overview] | Proportion of Patients With a Severe Asthma Exacerbation During 14 Days of Treatment |
| NCT02491684 (15) [back to overview] | Time to First Moderate Asthma Exacerbation During 30 Days Following Randomisation |
| NCT02491684 (15) [back to overview] | Time to First Severe Asthma Exacerbation During 30 Days Following Randomisation |
| NCT02491684 (15) [back to overview] | AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days |
| NCT02541409 (4) [back to overview] | Change in Insulin Resistance |
| NCT02541409 (4) [back to overview] | HCV Treatment Completion |
| NCT02541409 (4) [back to overview] | Serious Adverse Events |
| NCT02541409 (4) [back to overview] | Sustained Virologic Response (SVR) |
| NCT02577029 (1) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Considered Possibly or Probably Related to Treatment |
| NCT02584829 (6) [back to overview] | Count of Participants Who Displayed Persistence of Transferred T Cells in Blood and Tumor (Group Co2) |
| NCT02584829 (6) [back to overview] | Count of Participants That Displayed Evidence of Epitope Spreading |
| NCT02584829 (6) [back to overview] | Count of Participants Who Experienced Adverse Events, Evaluated According to the Current Guidelines in National Cancer Institute (NCI) Common Toxicity Criteria Version 4.0 |
| NCT02584829 (6) [back to overview] | Evidence of Response, Based on Median Time to New Metastasis |
| NCT02584829 (6) [back to overview] | Functional Capacity of Transferred T Cells (Group 2) |
| NCT02584829 (6) [back to overview] | Merkel Cell Carcinoma (MCC)-Specific Survival |
| NCT02587065 (11) [back to overview] | Number of Participants With Clinical Abnormal Laboratory Values |
| NCT02587065 (11) [back to overview] | Change From Baseline in Number of Participants With Adherence to Study Treatment at Weeks 12 and 24 |
| NCT02587065 (11) [back to overview] | Change From Baseline in Multiple Sclerosis International Quality of Life Questionnaire (MusiQoL) Score at Week 12 and 24 |
| NCT02587065 (11) [back to overview] | Change From Baseline in Fatigue Status Scale (FSS) Score at Weeks 12 and 24 |
| NCT02587065 (11) [back to overview] | Number of Participants With AE Stratified by Severity |
| NCT02587065 (11) [back to overview] | Change From Baseline in Convenience Satisfaction Score of Treatment Satisfaction Questionnaire to Medication (TSQM-9) at Week 12 |
| NCT02587065 (11) [back to overview] | Change From Baseline in Annualized Relapse Rate (ARR) at Week 24 |
| NCT02587065 (11) [back to overview] | Percent Change in Relapse-Free Participants at Week 24 |
| NCT02587065 (11) [back to overview] | Change From Baseline in the Score of All Domains of TSQM-9 at Week 24 |
| NCT02587065 (11) [back to overview] | Number of Participants With Adverse Events (AE) |
| NCT02587065 (11) [back to overview] | Change From Baseline in Adapted Sclerosis Treatment Concerns Questionnaire (MSTCQ) Score at Weeks 12 and 24 |
| NCT02593773 (2) [back to overview] | Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests |
| NCT02593773 (2) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs |
| NCT02622724 (30) [back to overview] | Other Secondary Efficacy Endpoints: Number of ICU-free Days |
| NCT02622724 (30) [back to overview] | Other Secondary Efficacy Endpoints: Days Free of Vasoactive Support |
| NCT02622724 (30) [back to overview] | Other Secondary Efficacy Endpoints: Days Free of Renal Support |
| NCT02622724 (30) [back to overview] | Other Secondary Efficacy Endpoints: Days Free of Organ Failure |
| NCT02622724 (30) [back to overview] | Other Secondary Efficacy Endpoint: Days Free of Mechanical Ventilation |
| NCT02622724 (30) [back to overview] | Neurological Functioning (6MWT) at Extended Long-term Follow-up |
| NCT02622724 (30) [back to overview] | Long-term Efficacy Endpoints Relating to Respiratory Functioning (FEV1) |
| NCT02622724 (30) [back to overview] | Long-term Efficacy Endpoints Relating to Neurological Functioning (6MWT) |
| NCT02622724 (30) [back to overview] | Long-term Efficacy Endpoint: Change in Quality of Life From Baseline to Day 180 |
| NCT02622724 (30) [back to overview] | Extended Long-term Follow-up Exploratory Endpoint: Change in Quality of Life From Baseline to Day 360 |
| NCT02622724 (30) [back to overview] | Extended Long-term Follow-up Endpoint: Respiratory Functioning (FEV1) at Day 360 |
| NCT02622724 (30) [back to overview] | Exploratory, Extended Long-term Follow-up: Overall Mortality at Day 360 |
| NCT02622724 (30) [back to overview] | Efficacy Endpoint: Mortality in Hospital |
| NCT02622724 (30) [back to overview] | Other Secondary Efficacy Endpoints: Number of Days in Hospital |
| NCT02622724 (30) [back to overview] | Efficacy Endpoint: Evaluation of Pharmacodynamic (PD) Using Myxovirus Resistance Protein A (MxA) Biomarker |
| NCT02622724 (30) [back to overview] | Efficacy Endpoint: All-cause Mortality |
| NCT02622724 (30) [back to overview] | Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28 |
| NCT02622724 (30) [back to overview] | Change in the Treatment-specific Exploratory Biomarker Cluster of Differentiation 73 (CD73) Concentration |
| NCT02622724 (30) [back to overview] | Evaluation of Safety: Physical Examination |
| NCT02622724 (30) [back to overview] | Evaluation of Safety: Laboratory Results |
| NCT02622724 (30) [back to overview] | Efficacy Endpoint: Mortality in ICU |
| NCT02622724 (30) [back to overview] | Post-Hoc Analyses Related to the Use of Concomitant Glucocorticoids Medications and Mortality at D28 |
| NCT02622724 (30) [back to overview] | Pharmacogenetic Analysis |
| NCT02622724 (30) [back to overview] | Exploratory Variables Relating to Efficacy: Composite Endpoint (Mortality and Days Free of Mechanical Ventilation) at Day 90 |
| NCT02622724 (30) [back to overview] | Evaluation of Safety: Vital Signs - Heart Rate |
| NCT02622724 (30) [back to overview] | Evaluation of Safety: Vital Signs - Body Temperature |
| NCT02622724 (30) [back to overview] | Evaluation of Safety: Vital Signs - Blood Pressure |
| NCT02622724 (30) [back to overview] | Evaluation of Safety: Adverse Events and Deaths |
| NCT02622724 (30) [back to overview] | Efficacy Endpoint: Presence of Neutralising Antibodies to IFN Beta-1a |
| NCT02622724 (30) [back to overview] | Changes in Levels of Potential Inflammatory Markers (PIMs) |
| NCT02627144 (4) [back to overview] | Percentage of Participants With Best Overall Tumor Response |
| NCT02627144 (4) [back to overview] | Progression-free Survival (PFS) Time |
| NCT02627144 (4) [back to overview] | Percentage of Participants With Disease Control |
| NCT02627144 (4) [back to overview] | Overall Survival (OS) Time |
| NCT02666768 (4) [back to overview] | Change From Baseline in Pain |
| NCT02666768 (4) [back to overview] | Percent Change From Baseline in Bone Mineral Density (BMD) |
| NCT02666768 (4) [back to overview] | Number of Participants With Treatment Related Adverse Events CTCAE v4.0 Grade 3 or Higher |
| NCT02666768 (4) [back to overview] | Change From Baseline in White Blood Cell Count (WBC) |
| NCT02716779 (12) [back to overview] | Time to Maximum Concentration (Tmax) of GPT |
| NCT02716779 (12) [back to overview] | Area Under the Concentration-Time Curve (AUC) of PEG-IFN |
| NCT02716779 (12) [back to overview] | Area Under the Concentration-Time Curve (AUC) of Glutamate-Pyruvate Transaminase (GPT) |
| NCT02716779 (12) [back to overview] | Maximum Concentration (Cmax) of PEG-IFN |
| NCT02716779 (12) [back to overview] | Maximum Concentration (Cmax) of Ribavirin |
| NCT02716779 (12) [back to overview] | Log Likelihood Median Values of Hepatitis C-Virus (HCV) Kinetic Models for Quantitative HCV Ribonucleic Acid (RNA) Measurement With Various Assumptions of Ribavirin Mechanism of Action |
| NCT02716779 (12) [back to overview] | Time to Maximum Concentration (Tmax) of PEG-IFN |
| NCT02716779 (12) [back to overview] | Time to Maximum Concentration (Tmax) of Ribavirin |
| NCT02716779 (12) [back to overview] | Area Under the Concentration-Time Curve (AUC) of Ribavirin |
| NCT02716779 (12) [back to overview] | Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire |
| NCT02716779 (12) [back to overview] | Percentage of Participants With Treatment Response |
| NCT02716779 (12) [back to overview] | Maximum Concentration (Cmax) of GPT |
| NCT02726789 (4) [back to overview] | Number of Patients Experiencing Reductions in Serum HBV DNA |
| NCT02726789 (4) [back to overview] | Number of Patients Experiencing Reductions in Serum HBsAg |
| NCT02726789 (4) [back to overview] | Number of Patients Experiencing Treatment Emergent Laboratory Test Abnormalities or Adverse Events. |
| NCT02726789 (4) [back to overview] | Number of Patients Experiencing Serum Anti-HBs > 10 mIU / ml |
| NCT02727907 (17) [back to overview] | Number of Combined Unique Active Lesions |
| NCT02727907 (17) [back to overview] | Number of Combined Unique Active Lesions |
| NCT02727907 (17) [back to overview] | Relapse Free Time |
| NCT02727907 (17) [back to overview] | Serious Adverse Events |
| NCT02727907 (17) [back to overview] | Annual Relapse Rate |
| NCT02727907 (17) [back to overview] | Severe Adverse Events Frequency |
| NCT02727907 (17) [back to overview] | Withdrawal |
| NCT02727907 (17) [back to overview] | Relapse Free Time |
| NCT02727907 (17) [back to overview] | Proportion of Subjects Without Confirmed Relapse |
| NCT02727907 (17) [back to overview] | Immunogenicity |
| NCT02727907 (17) [back to overview] | Severe Adverse Events Frequency |
| NCT02727907 (17) [back to overview] | Adverse Reaction/Serious Adverse Reactions |
| NCT02727907 (17) [back to overview] | Immunogenicity |
| NCT02727907 (17) [back to overview] | Adverse Events/Serious Adverse Events |
| NCT02727907 (17) [back to overview] | Annual Relapse Rate |
| NCT02727907 (17) [back to overview] | Number of Combined Unique Active Lesions |
| NCT02727907 (17) [back to overview] | Withdrawal |
| NCT02732639 (8) [back to overview] | Percentage of Participants With HBsAg Seronegative at Weeks 48 and 72 |
| NCT02732639 (8) [back to overview] | Number of Participants With Positive Hepatitis B Surface Antigen (HBsAg) Levels |
| NCT02732639 (8) [back to overview] | Percentage of Participants With Normal ALT at Week 48 |
| NCT02732639 (8) [back to overview] | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 72 |
| NCT02732639 (8) [back to overview] | Percentage of Participants With Negative Hepatitis D Virus Ribonucleic Acid (HDV RNA) at Week 72 |
| NCT02732639 (8) [back to overview] | Percentage of Participants With Negative HDV RNA at Week 48 |
| NCT02732639 (8) [back to overview] | Percentage of Participants With Positive Hepatitis B Surface Antibody (HBsAb) at Weeks 48 and 72 |
| NCT02732639 (8) [back to overview] | Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Below 1*10^5 Copies/Milliliter (mL) at Weeks 48 and 72 |
| NCT02761629 (8) [back to overview] | Percentage of Participants Without SVR Among Participants With Undetectable HCV RNA at the End of Treatment |
| NCT02761629 (8) [back to overview] | Percentage of Participants With Sustained Virologic Response (SVR) |
| NCT02761629 (8) [back to overview] | Serum Human Immunodeficiency Virus (HIV) RNA Levels |
| NCT02761629 (8) [back to overview] | Percentage of Participants With Undetectable HCV RNA 12 Weeks After the Last Dose of Peg-IFN-Alpha-2A |
| NCT02761629 (8) [back to overview] | Percentage of Participants With Undetectable HCV RNA |
| NCT02761629 (8) [back to overview] | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories |
| NCT02761629 (8) [back to overview] | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 |
| NCT02761629 (8) [back to overview] | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 |
| NCT02797080 (1) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs |
| NCT02829775 (2) [back to overview] | Number of Participants With Serious Adverse Events (SAEs) |
| NCT02829775 (2) [back to overview] | Number of Participants With Overall Tumor Response |
| NCT03063632 (7) [back to overview] | Incidence of Adverse Events |
| NCT03063632 (7) [back to overview] | Time to Response (TTR) |
| NCT03063632 (7) [back to overview] | Rate of Overall Response Duration Beyond 12 Months (ORR12) |
| NCT03063632 (7) [back to overview] | Progression-free Survival (PFS) |
| NCT03063632 (7) [back to overview] | Overall Response Rate (ORR) |
| NCT03063632 (7) [back to overview] | Event-free Survival (EFS) |
| NCT03063632 (7) [back to overview] | Duration of Response (DOR) |
| NCT03066947 (6) [back to overview] | Number of Patients With Treatment Emergent Adverse Events Occurring in Two or More Patients [Safety] |
| NCT03066947 (6) [back to overview] | Rate of Non-progression of Tumors |
| NCT03066947 (6) [back to overview] | Durability of Tumor Response |
| NCT03066947 (6) [back to overview] | Objective Tumor Response Rate |
| NCT03066947 (6) [back to overview] | Duration of Treatment Emergent Adverse Events [Safety] |
| NCT03066947 (6) [back to overview] | Number of Participants With an Adverse Event Related to SV-BR-1-GM Administration [Safety] |
| NCT03112590 (4) [back to overview] | Phase 1: Recommended Phase 2 Dose (RP2D) |
| NCT03112590 (4) [back to overview] | Phase 2: Clinical Response |
| NCT03112590 (4) [back to overview] | Phase 2: Progression Free Survival (PFS)/Number of Participants Who Progressed |
| NCT03112590 (4) [back to overview] | Phase 2: Pathologic Complete Response Rate (pCR) |
| NCT03119701 (14) [back to overview] | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples |
| NCT03119701 (14) [back to overview] | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis |
| NCT03119701 (14) [back to overview] | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) |
| NCT03119701 (14) [back to overview] | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) |
| NCT03119701 (14) [back to overview] | Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days |
| NCT03119701 (14) [back to overview] | Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters |
| NCT03119701 (14) [back to overview] | The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality |
| NCT03119701 (14) [back to overview] | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker |
| NCT03119701 (14) [back to overview] | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Organ Failure Free Days by Means of the Sequential Organ Failure Assessment (SOFA) Score |
| NCT03119701 (14) [back to overview] | The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality |
| NCT03119701 (14) [back to overview] | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs) |
| NCT03119701 (14) [back to overview] | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). |
| NCT03119701 (14) [back to overview] | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples |
| NCT03119701 (14) [back to overview] | Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples |
| NCT03368664 (3) [back to overview] | Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Months 4 and 8 |
| NCT03368664 (3) [back to overview] | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Participants With New or Enlarged T2 Lesions Per MRI Scan |
| NCT03368664 (3) [back to overview] | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan |
| NCT03403634 (4) [back to overview] | Progression Free Survival |
| NCT03403634 (4) [back to overview] | Overall Survival |
| NCT03403634 (4) [back to overview] | Change in Tumor-infiltrating Lymphocytes (TILs) in the Colorectal Cancer Lesions |
| NCT03403634 (4) [back to overview] | Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 |
| NCT03480932 (3) [back to overview] | Serious Adverse Events |
| NCT03480932 (3) [back to overview] | Medication Adherence |
| NCT03480932 (3) [back to overview] | SVR12 |
| NCT03537274 (2) [back to overview] | Number of Participants Achieving Sustained Responder Status at 24 Weeks of Follow-up |
| NCT03537274 (2) [back to overview] | Number of Participants Achieving Responder Status at 24 Weeks of Treatment |
| NCT03547154 (3) [back to overview] | Number of Participants With Cytogenetic Response (CR) to PEG Intron and Intron A at 6 Months |
| NCT03547154 (3) [back to overview] | Number of Participants With Overall Survival |
| NCT03547154 (3) [back to overview] | Number of Participants With Hematologic Responses to PEG Intron and Intron A at 6 Months |
| NCT03552549 (1) [back to overview] | Overall Survival |
| NCT03554005 (3) [back to overview] | Number of Participants Who Discontinued Treatment Due to an Adverse Event |
| NCT03554005 (3) [back to overview] | Number of Participants Who Experienced an Adverse Event |
| NCT03554005 (3) [back to overview] | Best Objective Response |
| NCT03600714 (12) [back to overview] | Number of Participants With Reduction in Fibroscan Transient Elastography Values |
| NCT03600714 (12) [back to overview] | Number of Participants With Normalization of Serum ALT |
| NCT03600714 (12) [back to overview] | Change in Quantitative Log HBsAg Levels From Baseline 24 Weeks After Completing Therapy |
| NCT03600714 (12) [back to overview] | Change in Quantitative Log HBsAg Levels From Baseline to Week 24 |
| NCT03600714 (12) [back to overview] | Number of Participants Who Discontinue Medication |
| NCT03600714 (12) [back to overview] | Number of Participants With Reduction in Histologic Inflammatory Scores (Modified HAI) |
| NCT03600714 (12) [back to overview] | Number of Participants With Decline of Hepatitis D Virus (HDV) RNA Viral Titer of >2 Logs |
| NCT03600714 (12) [back to overview] | Number of Participants With Loss of HBsAg at 24 Weeks After Completing Therapy |
| NCT03600714 (12) [back to overview] | Number of Participants With Loss of HBsAg at Week 12 Weeks After Completing Therapy |
| NCT03600714 (12) [back to overview] | Number of Participants With Loss of HBsAg at Week 24 |
| NCT03600714 (12) [back to overview] | Number of Participants With Reduction of Hepatic Venous Pressure Gradient (HVPG) |
| NCT03600714 (12) [back to overview] | Number of Participants With Sustained Virologic Response |
| NCT04081389 (4) [back to overview] | Number of Patients With Pathological Complete Response (pCR) |
| NCT04081389 (4) [back to overview] | Recurrence-free Survival (RFS) |
| NCT04081389 (4) [back to overview] | Overall Survival (OS) |
| NCT04081389 (4) [back to overview] | Number of Patients With Dose Limiting Toxicities |
| NCT04343976 (3) [back to overview] | Undetectable COVID PCR Testing at Day 14 |
| NCT04343976 (3) [back to overview] | Undetectable COVID PCR at Day 7 |
| NCT04343976 (3) [back to overview] | Undetectable COVID PCR at Day 3 |
| NCT04492475 (49) [back to overview] | Change From Baseline in Basophils |
| NCT04492475 (49) [back to overview] | Change From Baseline in Aspartate Aminotransferase (AST) |
| NCT04492475 (49) [back to overview] | Change From Baseline in Alanine Aminotransferase (ALT) |
| NCT04492475 (49) [back to overview] | Time to Recovery for Patients With a Baseline Ordinal Score of 4 and 5 |
| NCT04492475 (49) [back to overview] | Duration of Hospitalization |
| NCT04492475 (49) [back to overview] | Change in National Early Warning Score (NEWS) From Baseline |
| NCT04492475 (49) [back to overview] | Change From Baseline in C-reactive Protein (CRP) |
| NCT04492475 (49) [back to overview] | Time to an Improvement of One Category Using an Ordinal Scale |
| NCT04492475 (49) [back to overview] | Proportion of Participants With New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use |
| NCT04492475 (49) [back to overview] | Proportion of Participants With New Oxygen Use |
| NCT04492475 (49) [back to overview] | Proportion of Participants With New Non-invasive Ventilation or High Flow Oxygen Use |
| NCT04492475 (49) [back to overview] | Percentage of Participants Reporting Serious Adverse Events (SAEs) |
| NCT04492475 (49) [back to overview] | Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) |
| NCT04492475 (49) [back to overview] | 28-day Participant Mortality |
| NCT04492475 (49) [back to overview] | 14-day Participant Mortality |
| NCT04492475 (49) [back to overview] | Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 5 |
| NCT04492475 (49) [back to overview] | Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 1 |
| NCT04492475 (49) [back to overview] | Change From Baseline in Total Bilirubin |
| NCT04492475 (49) [back to overview] | Change From Baseline in Prothrombin International Normalized Ratio (INR) |
| NCT04492475 (49) [back to overview] | Change From Baseline in Platelets |
| NCT04492475 (49) [back to overview] | Change From Baseline in Neutrophils |
| NCT04492475 (49) [back to overview] | Change From Baseline in Monocytes |
| NCT04492475 (49) [back to overview] | Change From Baseline in Lymphoctyes |
| NCT04492475 (49) [back to overview] | Change From Baseline in Hemoglobin |
| NCT04492475 (49) [back to overview] | Change From Baseline in Eosinophils |
| NCT04492475 (49) [back to overview] | Change From Baseline in Creatinine |
| NCT04492475 (49) [back to overview] | Time to an Improvement of Two Categories Using an Ordinal Scale |
| NCT04492475 (49) [back to overview] | Time to Discharge or to a National Early Warning Score (NEWS) of |
| NCT04492475 (49) [back to overview] | Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 |
| NCT04492475 (49) [back to overview] | Change From Baseline in White Blood Cell Count (WBC) |
| NCT04492475 (49) [back to overview] | Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Sex |
| NCT04492475 (49) [back to overview] | Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Race |
| NCT04492475 (49) [back to overview] | Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Ethnicity |
| NCT04492475 (49) [back to overview] | Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 8 |
| NCT04492475 (49) [back to overview] | Change From Baseline in D-dimer Concentration |
| NCT04492475 (49) [back to overview] | Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 3 |
| NCT04492475 (49) [back to overview] | Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 29 |
| NCT04492475 (49) [back to overview] | Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 22 |
| NCT04492475 (49) [back to overview] | Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 15 |
| NCT04492475 (49) [back to overview] | Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 11 |
| NCT04492475 (49) [back to overview] | Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 for Participants With Baseline Ordinal Score 4 and 5 |
| NCT04492475 (49) [back to overview] | Number of Participants With Discontinuation or Temporary Suspension of Study Product Administration |
| NCT04492475 (49) [back to overview] | Mean Change From Baseline in the Ordinal Scale |
| NCT04492475 (49) [back to overview] | Duration of Oxygen Use |
| NCT04492475 (49) [back to overview] | Duration of Non Invasive Ventilation or High Flow Oxygen Use |
| NCT04492475 (49) [back to overview] | Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use |
| NCT04492475 (49) [back to overview] | Duration of New Oxygen Use |
| NCT04492475 (49) [back to overview] | Duration of New Non-invasive Ventilation or High Flow Oxygen Use |
| NCT04492475 (49) [back to overview] | Duration of Invasive Mechanical Ventilation |
| NCT04781647 (10) [back to overview] | Mean Change From Baseline HBV DNA |
| NCT04781647 (10) [back to overview] | Number of Participants With Premature Discontinuation of Treatment |
| NCT04781647 (10) [back to overview] | Mean Change From Baseline in HBsAg |
| NCT04781647 (10) [back to overview] | Number of Participants With a Laboratory Abnormality |
| NCT04781647 (10) [back to overview] | Mean Change From Baseline in HBV pgRNA |
| NCT04781647 (10) [back to overview] | Plasma Concentration of ABI-H0731 |
| NCT04781647 (10) [back to overview] | Mean Change From Baseline in HBeAg |
| NCT04781647 (10) [back to overview] | Mean Change From Baseline in HBcrAg |
| NCT04781647 (10) [back to overview] | Plasma Concentration of ABI-H0731 |
| NCT04781647 (10) [back to overview] | Number of Participants With an Adverse Event |
5-year Relapse-free Survival Rate
Relapse-free survival (RFS) was defined as time from randomization to disease relapse or death from any cause, whichever occurred first. Patients without disease relapse were censored at last disease assessment date known of free of relapse. Kaplan-Meier method was used to estimate 5-year RFS rate in the intent-to-treat (ITT) patients. (NCT00003641)
Timeframe: assessed every 3 months for 2 years, every 6 months for 3 years
| Intervention | proportion of participants (Number) |
|---|
| Observation | 0.70 |
| Interferon Alfa-2b | 0.70 |
5-year Overall Survival Rate
Overall survival (OS) was defined as time from randomization to death from any cause. Patients still alive were censored at last known alive date. Kaplan-Meier method was used to estimate 5-year OS rate in the ITT patients. (NCT00003641)
Timeframe: assessed every 3 months for 2 years, every 6 months for 3 years
| Intervention | proportion of participants (Number) |
|---|
| Observation | 0.83 |
| Interferon Alfa-2b | 0.83 |
Best Response as Measured by CT, Bone Scans, and Clinical Progression
(NCT00003656)
Timeframe: After 8 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Minor Reponse | Partial Response | Stable Disease | Disease Progression |
|---|
| Phase 1 Group | 1 | 0 | 1 | 5 | 5 |
,| Phase 2 Group | 0 | 1 | 3 | 4 | 6 |
Number of Subjects With Toxicity by Clinical Evaluation From First Dose to 30 Days After Last Dose
(NCT00003656)
Timeframe: In 30 days after the last dose, an average of 1 year.
| Intervention | Participants (Count of Participants) |
|---|
| Fatigue : Grade 1 | Fatigue : Grade 2 | Fatigue : Grade 3 | Fatigue : Grade 4 | Skin : Grade 1 | Skin : Grade 2 | Skin : Grade 3 | Skin : Grade 4 | Xeroderma : Grade 1 | Xeroderma : Grade 2 | Xeroderma : Grade 3 | Xeroderma : Grade 4 | Constipation : Grade 1 | Constipation : Grade 2 | Constipation : Grade 3 | Constipation : Grade 4 | Cough : Grade 1 | Cough : Grade 2 | Cough : Grade 3 | Cough : Grade 4 | Anemia : Grade 1 | Anemia : Grade 2 | Anemia : Grade 3 | Anemia : Grade 4 | Anorexia : Grade 1 | Anorexia : Grade 2 | Anorexia : Grade 3 | Anorexia : Grade 4 | Neurologic : Grade 1 | Neurologic : Grade 2 | Neurologic : Grade 3 | Neurologic : Grade 4 | Diarrhea : Grade 1 | Diarrhea : Grade 2 | Diarrhea : Grade 3 | Diarrhea : Grade 4 | Nausea/vomiting : Grade 1 | Nausea/vomiting : Grade 2 | Nausea/vomiting : Grade 3 | Nausea/vomiting : Grade 4 | Altered mood : Grade 1 | Altered mood : Grade 2 | Altered mood : Grade 3 | Altered mood : Grade 4 | Leukopenia : Grade 1 | Leukopenia : Grade 2 | Leukopenia : Grade 3 | Leukopenia : Grade 4 | Fever : Grade 1 | Fever : Grade 2 | Fever : Grade 3 | Fever : Grade 4 | Renal : Grade 1 | Renal : Grade 2 | Renal : Grade 3 | Renal : Grade 4 | Liver : Grade 1 | Liver : Grade 2 | Liver : Grade 3 | Liver : Grade 4 | Thrombocytopenia : Grade 1 | Thrombocytopenia : Grade 2 | Thrombocytopenia : Grade 3 | Thrombocytopenia : Grade 4 | Infusion reaction : Grade 1 | Infusion reaction : Grade 2 | Infusion reaction : Grade 3 | Infusion reaction : Grade 4 | Pulmonary : Grade 1 | Pulmonary : Grade 2 | Pulmonary : Grade 3 | Pulmonary : Grade 4 | Nasal congestion : Grade 1 | Nasal congestion : Grade 2 | Nasal congestion : Grade 3 | Nasal congestion : Grade 4 | Hypotension : Grade 1 | Hypotension : Grade 2 | Hypotension : Grade 3 | Hypotension : Grade 4 | Cholesterol/TG : Grade 1 | Cholesterol/TG : Grade 2 | Cholesterol/TG : Grade 3 | Cholesterol/TG : Grade 4 | Bone pain : Grade 1 | Bone pain : Grade 2 | Bone pain : Grade 3 | Bone pain : Grade 4 | Other pain : Grade 1 | Other pain : Grade 2 | Other pain : Grade 3 | Other pain : Grade 4 |
|---|
| Phase 1 Group | 7 | 5 | 0 | 0 | 1 | 0 | 0 | 0 | 11 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 4 | 2 | 0 | 0 | 3 | 1 | 2 | 0 | 9 | 2 | 0 | 0 | 8 | 3 | 1 | 0 | 5 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 8 | 0 | 0 | 0 | 2 | 2 | 3 | 0 | 4 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Phase 2 Group | 8 | 4 | 0 | 0 | 3 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 5 | 0 | 0 | 6 | 2 | 0 | 0 | 9 | 1 | 0 | 0 | 4 | 0 | 0 | 0 | 6 | 1 | 0 | 0 | 4 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 5 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 5 | 0 | 0 | 0 |
Duration of Response (Progression-free Survival) as Measured by CT, Bone Scans, and Clinical Progression From Initiation of Therapy Until an Increase of ≥ 25% From the Smallest Sum of All Tumor Measurements Obtained During the Best Response
(NCT00003656)
Timeframe: At 6 months and 12 months
| Intervention | Participants (Count of Participants) |
|---|
| 6 month | 12 month |
|---|
| Phase 1 Group | 5 | 4 |
,| Phase 2 Group | 7 | 3 |
Change in Retinoic Acid Receptor Expression on Tissue as Measured by Number of Subjects With the Presence of Peripheral Blood Lymphocytes During the First and Fifth Dose
(NCT00003656)
Timeframe: At baseline and 5th week
| Intervention | Participants (Count of Participants) |
|---|
| All Subjects | 0 |
Three-year Overall Survival
Kaplan-Meier estimate at three years post-first transplant of survival. Outcome is death or alive at follow-up (censored). 95 percent confidence interval of the point estimate is calculated using Greenwood's variance. (NCT00004088)
Timeframe: Estimate reported at three years after day 0 of the first cycle of infusion of cells of the tandem transplant.
| Intervention | proportion of participants (Number) |
|---|
| HD Chemo Followed by PBPC Rescue | 0.662 |
Progression-free Survival
"Kaplan-Meier estimate at three years post-first transplant of survival. Event of interest is the first of Death or Progression. Censoring is Alive in Continuous Complete Remission at date of last follow-up.~95 percent confidence interval of the point estimate is calculated using Greenwood's variance." (NCT00004088)
Timeframe: Estimate reported at three years after day 0 of the first cycle of infusion of cells of the tandem transplant.
| Intervention | proportion of participants (Number) |
|---|
| HD Chemo Followed by PBPC Rescue | 0.456 |
Toxicity
Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event (NCT00006237)
Timeframe: While on treatment, patients on the HDIFN arm were assessed weekly for the 1st month, then every 2 weeks for the 2nd month, then every 3 months therafter; patients on the biochemo arm were assessed daily for the 1st 5 days, then weekly thereafter.
| Intervention | Participants (Number) |
|---|
| Abdominal pain/cramping | Acidosis | Acute vascular leak syndrome | Alkaline phosphatase increase | Allergic reaction | Anal incontinence | Anemia | Anorexia | Anxiety/agitation | Apnea | Arrhythmia, NOS | Arthralgia | Bilirubin increase | Bone pain | CPK increase | Cardiovascular-other | Catheter related infection | Cerebrovascular ischemia | Colitis | Confusion | Constipation/bowel obstruction | Cranial neuropathy | Creatinine increase | Dehydration | Delusions | Depression | Diarrhea without colostomy | Dizziness/light headedness | Dizziness/vertigo, NOS | Double vision | Dyspnea | Eryth/rash/eruption/desq, NOS | Esophagitis/dysphagia | Eye-other | Fatigue/malaise/lethargy | Febrile neutropenia | Fever without neutropenia | Fever, NOS | Hallucinations | Headache | Hemorrhage w/ 3-4 thrombocyt | Hyperglycemia | Hyperkalemia | Hypermagnesemia | Hypertension | Hypertriglyceridemia | Hypocalcemia | Hypokalemia | Hypomagnesemia | Hyponatremia | Hypophosphatemia | Hypotension | Hypoxia | Infection w/o 3-4 neutropenia | Infection with 3-4 neutropenia | Infection, unk ANC | Insomnia | Leukopenia | Lipase increase | Local injection site reaction | Lymphopenia | Mood/consciousness change, NOS | Muscle weakness (not neuro) | Myalgia | Nausea | Neutropenia/granulocytopenia | PRBC transfusion | Pancreatitis | Personality/behavioral change | Petechiae/purpura | Platelet transfusion | Pruritus | Rash/desquamation | Renal failure | Reportable adverse event, NOS | Respiratory infect w/ neutrop | Rigors/chills | SGOT (AST) increase | SGPT (ALT) increase | Seizures | Sensory neuropathy | Stomatitis/pharyngitis | Surgery-wound infection | Syncope | Thrombocytopenia | Thrombosis/embolism | Typhlitis | Vertigo | Vomiting | Weakness (motor neuropathy) | Weight loss |
|---|
| Biochemotherapy | 1 | 1 | 1 | 3 | 0 | 1 | 8 | 9 | 5 | 0 | 0 | 3 | 1 | 4 | 1 | 0 | 2 | 0 | 2 | 3 | 4 | 0 | 4 | 7 | 1 | 4 | 6 | 1 | 1 | 1 | 2 | 3 | 2 | 0 | 22 | 9 | 5 | 1 | 1 | 5 | 1 | 3 | 1 | 1 | 1 | 0 | 18 | 7 | 5 | 6 | 4 | 16 | 1 | 3 | 9 | 2 | 1 | 38 | 2 | 0 | 2 | 1 | 1 | 4 | 51 | 61 | 3 | 1 | 0 | 1 | 5 | 3 | 10 | 1 | 1 | 2 | 1 | 7 | 8 | 2 | 2 | 1 | 0 | 0 | 50 | 1 | 1 | 0 | 37 | 2 | 0 |
,| Interferon | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 4 | 1 | 2 | 4 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 14 | 2 | 2 | 0 | 0 | 1 | 1 | 0 | 1 | 38 | 1 | 1 | 0 | 1 | 9 | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 12 | 1 | 1 | 0 | 0 | 0 | 7 | 10 | 25 | 0 | 0 | 1 | 0 | 0 | 1 | 4 | 0 | 1 | 0 | 2 | 18 | 32 | 0 | 0 | 0 | 3 | 2 | 1 | 1 | 0 | 1 | 9 | 1 | 3 |
5-year Relapse-Free Survival
Measured from date of registration to date of first observation of progressive disease or death due to any cause. (NCT00006237)
Timeframe: Every three months for the first year, every 6 months for years 2-5, annually for years 6-10
| Intervention | Percentage of population (Number) |
|---|
| Interferon | 47 |
| Biochemotherapy | 38 |
5-year Overall Survival
Overall survival was measured from the date of registration to study until death from any cause with observations censored at the date of last contact for patients last known to be alive. (NCT00006237)
Timeframe: Every three months for a year, every six months for years 2-5, annual for years 5-10
| Intervention | Percent of population (Number) |
|---|
| Interferon | 56 |
| Biochemotherapy | 56 |
Initial Response to Therapy
Evaluate initial response to therapy (complete remission, partial remission, stable response, or progression of disease) (NCT00006244)
Timeframe: Evaluated at Day +84-90 Post-Transplant
| Intervention | Participants (Count of Participants) |
|---|
| Patients in Complete Remission | Patients in Partial Remission | Patients with Stable resposne | Patients with Disease Progression |
|---|
| Immunotherapy Treatment | 15 | 8 | 10 | 3 |
Overall Survival
Overall survival in Multiple Myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2 and interferon maintenance. (NCT00006244)
Timeframe: 12.9 Median Years
| Intervention | Participants (Count of Participants) |
|---|
| Immunotherapy Treatment | 9 |
Proportion of Patients Alive and in Remission
(NCT00006244)
Timeframe: 12.9 Median Years
| Intervention | Participants (Count of Participants) |
|---|
| Immunotherapy Treatment | 4 |
Time to Disease Progression
(NCT00006244)
Timeframe: 12.9 years (median)
| Intervention | years (Median) |
|---|
| Immunotherapy Treatment | 1.61 |
Major Cytogenetic Response After 6 and 12 Months of Treatment.
"Cytogenetic response in terms of the percentage of Ph chromosome positive metaphases in bone marrow is defined as follows:~Complete* (0% Ph-positive cells) Partial* (1-34%) Minor (35-95%) None (96-100%).~*Major cytogenetic response includes complete and partial cytogenetic response." (NCT00015847)
Timeframe: 6 and 12 months after treatment
| Intervention | Participants (Number) |
|---|
| Imatinib Mesylate | 18 |
Complete Cytogenetic Response at 6 and 12 Months (Phase II)
"Cytogenetic response in terms of the percentage of Ph chromosome positive metaphases in bone marrow is defined as follows:~Complete* (0% Ph-positive cells) Partial* (1-34%) Minor (35-95%) None (96-100%)." (NCT00015847)
Timeframe: At 6 and 12 months during phase II
| Intervention | Participants (Number) |
|---|
| Imatinib Mesylate | 13 |
Comparison of Plasma Levels of VEGF Following Administration of Bevacizumab Alone or in Combination With IFN-alfa
Analyzed by Enzyme-Linked Immunosorbent Assay (ELISA).VEGF only analyzed at baseline. (NCT00026221)
Timeframe: At baseline
| Intervention | pg/mL (Median) |
|---|
| Arm I: Bevacizumab + Iinterferon-alpha-2b | 567 |
| Arm II: Bevacizumab Alone | 633 |
| Arm III (Monoclonal Antibody and Biological Therapy) | 18 |
Objective Response Rate
Measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. (NCT00026221)
Timeframe: Up to 2 years
| Intervention | patients (Number) |
|---|
| Arm I: Bevacizumab + Iinterferon-alpha-2b | 1 |
| Arm II: Bevacizumab Alone | 0 |
| Arm III (Monoclonal Antibody and Biological Therapy) | 6 |
Progression-free Survival
Defined as the time from treatment start date until documentation of progressive disease. Evaluated using the new international criteria proposed by the RECIST Committee. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT00026221)
Timeframe: Up to 2 years
| Intervention | months (Median) |
|---|
| Arm I: Bevacizumab + Iinterferon-alpha-2b | 3 |
| Arm II: Bevacizumab Alone | 8.5 |
| Arm III (Monoclonal Antibody and Biological Therapy) | 4.8 |
Two Year Survival of Pediatric Patients With Diffuse Pontine Gliomas
Survival is measured from the date the patient is registered onto the protocol until the day of death and the date of diagnosis to the date of patient death. (NCT00036569)
Timeframe: 8 yrs 6 mo 0 days
| Intervention | Percentage of patients (Number) |
|---|
| Interferon Alfa | 14.29 |
Number of Participants With Adverse Events
Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module. (NCT00036569)
Timeframe: 8 yrs 11 mo 22 days
| Intervention | Participants (Number) |
|---|
| Interferon Alfa | 32 |
Mean Quality of Life (QOL) Score at Baseline and Follow-Up
QOL questionnaires will be performed prior to every cycle for patients age 6-18 years and their parents until cycle 27 and then prior to every third cycle until cycle 52 when the evaluations will become annual. The QOL (NIH Impact of Pediatric Illness Scale) is too detailed to be described and/or shown here. It is a questionnaire made up of approximately 40 questions-the answers are ranked from 1 to 5 with 5 being no impact and 1 being significant impact-For further details see the protocol. (NCT00036569)
Timeframe: once a week for 4 weeks beginning 2-10 weeks after completion of radiation therapy and continued until disease progression or one of the other off study criteria.
| Intervention | Units on a scale (Mean) |
|---|
| QOL Score at Baseline | 3.59 |
| QOL Score at Follow-up | 3.89 |
The Number of Participants With Adverse Events
Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module. (NCT00047879)
Timeframe: 4 months
| Intervention | Participants (Number) |
|---|
| Glioblastoma Multiforme Stratum | 4 |
| Anaplastic Glioma Stratum | 2 |
Non-progression Rate (Clinical Response to Peginterferon Alfa-2b)
"Objective tumor response was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Per RECIST criteria, complete response (CR) = disappearance of all target and non-target lesions. Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Progression is defined as at least 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing non-target lesions. Stable disease (SD) = did not meet criteria for response or progression.~Non-progression rate = CR + PR + SD." (NCT00049530)
Timeframe: assessed every 9 weeks until suppression of plasma b-FGF level to normal, every 12 weeks until the completion of 12 months of treatment, >= 4 weeks after documented response. After off treatment, every 3 months if <2 years, and every 6 months if 2-3 years
| Intervention | percentage of participants (Number) |
|---|
| PEG-interferon Alfa-2b | 24.1 |
Progression Free Survival
Progression free survival (PFS) was defined as the time from registration to disease progression, or censored at last known date of non progressive disease. (NCT00049530)
Timeframe: assessed every 9 weeks until suppression of plasma b-FGF level to normal, every 12 weeks until the completion of 12 months of treatment, >= 4 weeks after documented response. After off treatment, every 3 months if <2 years, and every 6 months if 2-3 years
| Intervention | months (Median) |
|---|
| PEG-interferon Alfa-2b | 2 |
Plasma b-FGF Level Response
The primary endpoint was the suppression of plasma b-FGF level with low dose peginterferon alfa-2b. A clinically important reduction of plasma b-FGF levels was determined to be a level less than or equal to 7.5 pg/mL. A patient was considered to have a suppressed plasma b-FGF level, if the patient experienced the clinically significant reduction (less than or equal to 7.5 pg/mL) of plasma b-FGF levels for two consecutive determinations which were at least three weeks apart. This was considered as a b-FGF response. (NCT00049530)
Timeframe: assessed every 3 weeks until the suppression of plasma b-FGF level to normal, then every 6 weeks until the completion of 12 months of treatment, and upon treatment discontinuation
| Intervention | percentage of participants (Number) |
|---|
| PEG-interferon Alfa-2b | 34.5 |
Overall Survival
Overall survival (OS) time was defined as the time from registration to death from any cause, or censored at last known date of survival. (NCT00049530)
Timeframe: assessed every 3 months if <2 years, and every 6 months if 2-3 years
| Intervention | months (Median) |
|---|
| PEG-interferon Alfa-2b | 9.7 |
Annualized Relapse Rate
Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated using a Poisson regression model with observed number of relapses as a dependent variable, the log total amount of follow-up from date of randomization for each participant as an offset variable and treatment group indicator as a covariate. (NCT00050778)
Timeframe: Up to 3 years
| Intervention | relapses per participant per year (Number) |
|---|
| Interferon Beta-1a | 0.37 |
| Alemtuzumab 12 mg | 0.12 |
| Alemtuzumab 24 mg | 0.09 |
| Alemtuzumab (Pooled) | 0.11 |
Percent Change From Baseline in MRI T2 Lesion Volume at Year 3
Percent change in lesion volume at Year 3 was calculated from MRI-T2-weighted scans as: 100*([lesion volume at Year 3] minus [lesion volume at Baseline]) divided by [lesion volume at Baseline]). (NCT00050778)
Timeframe: Baseline, Year 3
| Intervention | percent change (Mean) |
|---|
| Interferon Beta-1a | 23.4 |
| Alemtuzumab 12 mg | -11.4 |
| Alemtuzumab 24 mg | -8.9 |
| Alemtuzumab (Pooled) | -10.1 |
Percent Change From Baseline in T1 Cerebral Volume at Year 3
Magnetic resonance imaging (MRI) T1 was used to determine rate of cerebral atrophy (decrease in cerebral/brain volume). Partial brain volumes were measured using the technique of Losseff et al. (1996). Percent change in cerebral volume at Year 3 was calculated from MRI-T1-weighted scans as: 100*([brain volume at Year 3] minus [brain volume at Baseline]) divided by [brain volume at Baseline]). (NCT00050778)
Timeframe: Baseline, Year 3
| Intervention | percent change (Mean) |
|---|
| Interferon Beta-1a | -1.9 |
| Alemtuzumab 12 mg | -0.8 |
| Alemtuzumab 24 mg | -0.4 |
| Alemtuzumab (Pooled) | -0.6 |
Probability of Participants Who Were Relapse Free at 3 Years After Initial Treatment
Participants were considered relapse free at Year 3 if they did not experience a relapse between randomization and study completion at 36 months. Participants who discontinued early were considered relapse free if they did not experience a relapse prior to discontinuation. Probability of participants who were relapse free at Year 3, estimated using the KM method, was reported. (NCT00050778)
Timeframe: Year 3
| Intervention | probability of participants (Number) |
|---|
| Interferon Beta-1a | 0.50 |
| Alemtuzumab 12 mg | 0.76 |
| Alemtuzumab 24 mg | 0.84 |
| Alemtuzumab (Pooled) | 0.80 |
Probability of Participants With Sustained Accumulation of Disability (SAD)
EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with Baseline score of 1.0 or more; and the increase persisted for at least next the 2 scheduled assessments, that is, 6 consecutive months. The onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Probability of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported. (NCT00050778)
Timeframe: Up to 3 years
| Intervention | probability of participants with SAD (Number) |
|---|
| Interferon Beta-1a | 0.27 |
| Alemtuzumab 12 mg | 0.08 |
| Alemtuzumab 24 mg | 0.09 |
| Alemtuzumab (Pooled) | 0.09 |
Progression-free Survival
Time from registration to documented disease progression (RECIST criteria) or death. (NCT00062010)
Timeframe: Assessed every 6 weeks
| Intervention | months (Median) |
|---|
| IFN 13CRA Paclitaxel | 2.0 |
Survival
Time from registration to death. (NCT00062010)
Timeframe: Assessed every 3 months for 1 year then every 6 months
| Intervention | months (Median) |
|---|
| IFN 13CRA Paclitaxel | 6.2 |
Response by RECIST Criteria (v 1.0)
Number of eligible, treated participants in each response category by RECIST criteria (NCT00062010)
Timeframe: Assessed every 6 weeks
| Intervention | participants (Number) |
|---|
| Partial Response | Stable Disease | Progressive Disease | Unevaluable |
|---|
| IFN 13CRA Paclitaxel | 3 | 5 | 11 | 15 |
Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST)
"The Q-Twist is not a score calculated for each participant but is defined only on a by treatment group basis. For each treatment group, it is the weighted sum of the mean durations of the health states Tox, Twist, and Relapse. Tox is defined as time with severe toxicity related to treatment; Twist: time without symptoms or toxic side effects; and Relapse: time after relapse/progression. The mean duration of each health state is calculated based on the area under the Kaplan Meier curve pertaining to that health state. There is no direct method for calculating the dispersion of Q-Twist, and it is typically done using bootstrap method for purposes of inference (see, e.g., Glasziou PP, Simes RJ, Gelber RD. Quality adjusted survival analysis. Stat Med 1990; 9: 1259-76). In practice, as apparently in the case with this study, the intermediate values resulting from the bootstrap exercise were not displayed." (NCT00065468)
Timeframe: Baseline to Month 80
| Intervention | months (Number) |
|---|
| Interferon Alfa | 6.9083 |
| Temsirolimus | 8.3707 |
| Interferon Alfa and Temsirolimus | 7.4821 |
Time to Treatment Failure (TTF)
TTF is defined as the time from the date of randomization to the date of PD or death, withdrawal from treatment due to an adverse event (AE), withdrawal of voluntary consent, or lost to follow-up, whichever occurred first, censored at the date of the conclusion of treatment phase. (NCT00065468)
Timeframe: Baseline, every month until tumor progression or death (up to Month 80)
| Intervention | months (Median) |
|---|
| Interferon Alfa | 1.9 |
| Temsirolimus | 3.7 |
| Interferon Alfa and Temsirolimus | 2.5 |
European Quality of Life Health Questionnaire (EQ-5D) - Index Score
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. EQ-5D index measured 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Range of EQ-5D index score = -0.594 to 1 where higher scores indicated a better health state. (NCT00065468)
Timeframe: Baseline
| Intervention | units on a scale (Median) |
|---|
| Interferon Alfa | 0.656 |
| Temsirolimus | 0.689 |
| Interferon Alfa and Temsirolimus | 0.689 |
Duration of Response (DR)
DR: Time from first documentation of objective tumor response to first date that recurrence or progressive disease (PD) was objectively documented, taking as a reference for PD, the smallest sum LD recorded since randomization. (NCT00065468)
Timeframe: Baseline, every month until tumor progression or death (up to Month 80)
| Intervention | months (Median) |
|---|
| Interferon Alfa | 7.4 |
| Temsirolimus | 11.1 |
| Interferon Alfa and Temsirolimus | 9.3 |
Overall Survival (OS)
Overall survival is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact. (NCT00065468)
Timeframe: Baseline up to Month 80
| Intervention | months (Median) |
|---|
| Interferon Alfa | 7.3 |
| Temsirolimus | 10.9 |
| Interferon Alfa and Temsirolimus | 8.4 |
Percentage of Participants With Clinical Benefit
Clinical benefit: confirmed CR or PR or had stable disease (SD) lasting at least 24 weeks. CR was the disappearance of all target lesions and non target lesions. PR was at least a 30% decrease in sum of the LD of target lesions, taking as reference the baseline sum LD. SD was having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT00065468)
Timeframe: Baseline, every 2 months until tumor progression or death (up to Month 80)
| Intervention | percentage of participants (Number) |
|---|
| Interferon Alfa | 16.4 |
| Temsirolimus | 34.0 |
| Interferon Alfa and Temsirolimus | 30.0 |
Percentage of Participants With Objective Response
Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was the disappearance of all target lesions and non target lesions. PR was at least a 30 percent (%) decrease in sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. (NCT00065468)
Timeframe: Baseline, every 2 months until tumor progression or death (up to Month 80)
| Intervention | percentage of participants (Number) |
|---|
| Interferon Alfa | 5.3 |
| Temsirolimus | 9.1 |
| Interferon Alfa and Temsirolimus | 9.5 |
Progression-Free Survival (PFS)
PFS based on Independent Central Review Assessment. The period from randomization until disease progression, death or date of last contact. (NCT00065468)
Timeframe: Baseline, monthly until tumor progression or death (up to Month 80)
| Intervention | months (Median) |
|---|
| Interferon Alfa | 3.2 |
| Temsirolimus | 5.6 |
| Interferon Alfa and Temsirolimus | 4.9 |
Time to First Relapse
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. These new or worsening symptoms should be noted by subject and must be accompanied by at least 1 of the following: An increase of greater than or equal to (>=) 1 grade in >=2 functional scales of the Expanded Disability Status Scale (EDSS) or an increase of >=2 grades in 1 functional scale of the EDSS or an increase of >= 0.5 or an increase of >=1.0 in EDSS if the previous EDSS was 0. Time to first relapse was defined as the time in days from the date of first dose of study treatment to the date of first multiple sclerosis relapse. The mean time to first relapse for the 25th percentile and the 30th percentile during the 96-week treatment period was measured by Kaplan-Meier estimates and was reported. (NCT00078338)
Timeframe: Baseline up to 96 weeks
| Intervention | days (Mean) |
|---|
| 25th Percentile | 30th Percentile |
|---|
| Copaxone® | 290.0 | 432.0 |
,| Rebif® | 332.0 | 495.0 |
Overall Survival
Overall Survival at six years after initiating protocol therapy (NCT00083551)
Timeframe: 6 Years
| Intervention | percentage of participants (Number) |
|---|
| Thalidomide | 65 |
| No Thalidomide | 58 |
Plasma Concentrations of Soluble Proteins: Plasma Basic Fibroblast Growth Factor (bFGF) That May be Associated With Tumor Proliferation or Angiogenesis
Plasma concentrations of soluble proteins that may be associated with tumor proliferation or angiogenesis collected from a subset of patients were analyzed by enzyme-linked immunosorbent assay (ELISA) analysis. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio = plasma concentration of soluble protein (picograms per milliliter [pg/ml]) at timepoint / concentration of soluble protein (pg/ml) at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded. (NCT00083889)
Timeframe: Day 1 & Day 28, Cycle 1 to Cycle 4
| Intervention | pg/ml and ratio to Baseline (Mean) |
|---|
| PLASMA bFGF: C2D28:C1D1 (n=14, 0) | PLASMA bFGF: C3D1:C1D1 (n=12, 0) | PLASMA bFGF: C3D28:C1D1 (n=12, 0) | PLASMA bFGF: C4D1:C1D1 (n=14, 0) | PLASMA bFGF: C4:D28:C1D1 (n=10, 0) |
|---|
| SU011248 | 0.760 | 1.582 | 1.671 | 2.895 | 0.803 |
Functional Assessment of Cancer Therapy-General (FACT-G): Social/Family Well Being (SWB) Subscale
Social/family well-being (SWB)subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 28; lower score indicates less social/family well-being. (NCT00083889)
Timeframe: Day 1 & 28 of each cycle: duration of treatment phase
| Intervention | scores on scale (Mean) |
|---|
| Baseline (n=370, 349) | Cycle 1 Day 28 (n=348, 319) | Cycle 2 Day 1 (n=328, 247) | Cycle 2 Day 28 (n=315, 238) | Cycle 3 Day 1 (n=292, 200) | Cycle 3 Day 28 (n=284, 194) | Cycle 4 Day 1 (n=269, 150) | Cycle 4 Day 28 (n=263, 142) | Cycle 5 Day 1 (n=247, 120) | Cycle 5 Day 28 (n=241, 107) | Cycle 6 Day 1 (n=238, 98) | Cycle 6 Day 28 (n=224, 97) | Cycle 7 Day 1 (n=207, 79) | Cycle 7 Day 28 (n=200, 75) | Cycle 8 Day 1 (n=193, 67) | Cycle 8 Day 28 (n=189, 61) | Cycle 9 Day 1 (n=172, 51) | Cycle 9 Day 28 (n=166, 46) | Cycle 10 Day 1 (n=158, 49) | Cycle 10 Day 28 (n=151, 46) | Cycle 11 Day 1 (n=135, 35) | Cycle 11 Day 28 (n=140, 32) | Cycle 12 Day 1 (n=131, 30) | Cycle 12 Day 28 (n=127, 31) | Cycle 13 Day 1 (n=114, 27) | Cycle 13 Day 28 (n=114, 27) | Cycle 14 Day 1 (n=112, 26) | Cycle 14 Day 28 (n=107, 24) | Cycle 15 Day 1 (n=101, 21) | Cycle 15 Day 28 (n=96, 20) | Cycle 16 Day 1 (n=94, 19) | Cycle 16 Day 28 (n=89, 18) | Cycle 17 Day 1 (n=85, 16) | Cycle 17 Day 28 (n=80, 14) | Cycle 18 Day 1 (n=79, 12) | Cycle 18 Day 28 (n=70, 11) | Cycle 19 Day 1 (n=71, 11) | Cycle 19 Day 28 (n=61, 10) | Cycle 20 Day 1 (n=63, 9) | Cycle 20 Day 28 (n=52, 8) |
|---|
| IFN-α | 22.94 | 22.20 | 22.31 | 22.22 | 22.42 | 22.12 | 22.26 | 22.38 | 22.35 | 22.36 | 22.56 | 22.33 | 22.46 | 22.10 | 21.95 | 22.17 | 22.74 | 21.96 | 22.45 | 22.06 | 21.51 | 21.09 | 20.79 | 21.25 | 20.93 | 21.30 | 21.51 | 20.32 | 20.35 | 20.23 | 21.41 | 21.52 | 22.25 | 21.75 | 21.71 | 21.27 | 21.30 | 20.73 | 21.26 | 20.67 |
,| SU011248 | 23.14 | 23.60 | 23.50 | 23.40 | 23.51 | 23.44 | 23.73 | 23.36 | 23.53 | 23.68 | 23.35 | 23.40 | 23.29 | 23.13 | 23.67 | 23.26 | 23.26 | 23.26 | 23.08 | 23.03 | 23.05 | 22.71 | 23.23 | 23.07 | 23.15 | 23.31 | 22.82 | 23.24 | 23.28 | 23.04 | 23.11 | 23.41 | 23.42 | 23.50 | 23.53 | 23.70 | 23.85 | 23.53 | 23.60 | 22.93 |
Functional Assessment of Cancer Therapy-General (FACT-G): Physical Well Being (PWB) Subscale
Physical well-being (PWB) subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 28; lower score indicates better physical well-being. (NCT00083889)
Timeframe: Day 1 & 28 of each cycle: duration of treatment phase
| Intervention | scores on scale (Mean) |
|---|
| Baseline (n=369, 348) | Cycle 1 Day 28 (n=348, 318) | Cycle 2 Day 1 (n=329, 247) | Cycle 2 Day 28 (n=316, 239) | Cycle 3 Day 1 (n=294, 200) | Cycle 3 Day 28 (n=286, 195) | Cycle 4 Day 1 (n=270, 150) | Cycle 4 Day 28 (n=264, 142) | Cycle 5 Day 1 (n=248, 120) | Cycle 5 Day 28 (n=241, 106) | Cycle 6 Day 1 (n=239, 99) | Cycle 6 Day 28 (n=224, 97) | Cycle 7 Day 1 (n=207, 79) | Cycle 7 Day 28 (n=201, 75) | Cycle 8 Day 1 (n=193, 67) | Cycle 8 Day 28 (n=189, 61) | Cycle 9 Day 1 (n=172, 51) | Cycle 9 Day 28 (n=166, 46) | Cycle 10 Day 1 (n=159, 49) | Cycle 10 Day 28 (n=151, 46) | Cycle 11 Day 1 (n=135, 35) | Cycle 11 Day 28 (n=140, 32) | Cycle 12 Day 1 (n=131, 30) | Cycle 12 Day 28 (n=127, 31) | Cycle 13 Day 1 (n=114, 27) | Cycle 13 Day 28 (n=114, 27) | Cycle 14 Day 1 (n=112, 26) | Cycle 14 Day 28 (n=107, 24) | Cycle 15 Day 1 (n=101, 21) | Cycle 15 Day 28 (n=96, 20) | Cycle 16 Day 1 (n=94, 19) | Cycle 16 Day 28 (n=90, 18) | Cycle 17 Day 1 (n=85, 16) | Cycle 17 Day 28 (n=80, 14) | Cycle 18 Day 1 (n=79, 12) | Cycle 18 Day 28 (n=70, 11) | Cycle 19 Day 1 (n=71, 11) | Cycle 19 Day 28 (n=61, 10) | Cycle 20 Day 1 (n=63, 9) | Cycle 20 Day 28 (n=52, 9) |
|---|
| IFN-α | 22.70 | 18.85 | 20.05 | 19.84 | 20.87 | 20.63 | 21.56 | 21.31 | 21.84 | 21.23 | 21.70 | 20.96 | 21.67 | 21.66 | 21.94 | 21.40 | 22.58 | 22.38 | 22.60 | 21.83 | 22.23 | 21.88 | 22.60 | 21.90 | 21.99 | 21.80 | 22.05 | 22.75 | 22.33 | 22.07 | 20.63 | 21.42 | 21.81 | 20.50 | 21.83 | 22.45 | 22.45 | 21.60 | 21.78 | 22.33 |
,| SU011248 | 23.14 | 19.43 | 22.22 | 20.34 | 22.45 | 20.18 | 22.72 | 21.00 | 23.24 | 20.91 | 22.99 | 21.22 | 23.05 | 21.22 | 23.58 | 21.51 | 23.41 | 21.29 | 22.94 | 21.21 | 23.16 | 20.98 | 23.03 | 20.87 | 23.05 | 21.26 | 23.02 | 20.80 | 23.26 | 20.95 | 22.60 | 21.31 | 22.99 | 21.68 | 22.85 | 20.89 | 23.20 | 21.82 | 23.68 | 21.81 |
Functional Assessment of Cancer Therapy-General (FACT-G): Functional Well Being (FWB) Subscale
Functional well-being (FWB) subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 28; higher score indicates greater functional well-being. (NCT00083889)
Timeframe: Day 1 & 28 of each cycle: duration of treatment phase
| Intervention | scores on scale (Mean) |
|---|
| Baseline (n=371, 353) | Cycle 1 Day 28 (n=347, 318) | Cycle 2 Day 1 (n=328, 249) | Cycle 2 Day 28 (n=315, 238) | Cycle 3 Day 1 (n=294, 200) | Cycle 3 Day 28 (n=287, 195) | Cycle 4 Day 1 (n=272, 152) | Cycle 4 Day 28 (n=265, 142) | Cycle 5 Day 1 (n=249, 120) | Cycle 5 Day 28 (n=241, 109) | Cycle 6 Day 1 (n=239, 99) | Cycle 6 Day 28 (n=222, 99) | Cycle 7 Day 1 (n=208, 79) | Cycle 7 Day 28 (n=204, 75) | Cycle 8 Day 1 (n=192, 67) | Cycle 8 Day 28 (n=190, 62) | Cycle 9 Day 1 (n=170, 51) | Cycle 9 Day 28 (n=167, 46) | Cycle 10 Day 1 (n=161, 50) | Cycle 10 Day 28 (n=154, 46) | Cycle 11 Day 1 (n=137, 35) | Cycle 11 Day 28 (n=140, 33) | Cycle 12 Day 1 (n=132, 30) | Cycle 12 Day 28 (n=128, 31) | Cycle 13 Day 1 (n=114, 27) | Cycle 13 Day 28 (n=114, 27) | Cycle 14 Day 1 (n=114, 26) | Cycle 14 Day 28 (n=107, 25) | Cycle 15 Day 1 (n=101, 21) | Cycle 15 Day 28 (n=96, 20) | Cycle 16 Day 1 (n=96, 19) | Cycle 16 Day 28 (n=91, 18) | Cycle 17 Day 1 (n=85, 17) | Cycle 17 Day 28 (n=81, 14) | Cycle 18 Day 1 (n=80, 12) | Cycle 18 Day 28 (n=71, 11) | Cycle 19 Day 1 (n=71, 11) | Cycle 19 Day 28 (n=61, 10) | Cycle 20 Day 1 (n=65, 9) | Cycle 20 Day 28 (n=53, 9) |
|---|
| IFN-α | 18.51 | 16.37 | 17.08 | 17.18 | 17.92 | 17.56 | 18.40 | 18.37 | 18.81 | 18.47 | 19.02 | 18.24 | 18.45 | 18.76 | 19.22 | 19.10 | 20.20 | 20.04 | 19.88 | 19.40 | 18.89 | 18.81 | 18.80 | 19.13 | 19.63 | 18.59 | 19.62 | 19.72 | 19.86 | 19.83 | 18.89 | 18.61 | 19.35 | 18.71 | 19.08 | 19.00 | 19.64 | 19.10 | 20.00 | 20.22 |
,| SU011248 | 18.93 | 17.92 | 18.78 | 18.37 | 19.51 | 18.58 | 19.93 | 18.86 | 20.27 | 19.02 | 19.74 | 19.21 | 19.69 | 19.12 | 20.29 | 19.33 | 19.87 | 19.27 | 19.95 | 19.22 | 19.81 | 19.12 | 19.98 | 19.42 | 20.02 | 19.65 | 20.04 | 19.07 | 20.13 | 19.24 | 19.80 | 19.53 | 20.20 | 19.67 | 19.76 | 19.47 | 20.18 | 19.59 | 20.50 | 20.15 |
Time to Tumor Progression (TTP), Investigator's Assessment
TTP = time from randomization to first documentation of objective tumor progression. TTP data were censored on the day following the date of last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects who did not have objective tumor progression while on treatment or who were given anti-tumor treatment other than the study treatment prior to documentation of objective tumor progression. Subjects with no tumor assessments after randomization had TTP censored on the date of randomization with a duration of 1 day. (NCT00083889)
Timeframe: Randomization to first documentation of tumor progression: duration of treatment phase
| Intervention | weeks (Median) |
|---|
| SU011248 | 49.0 |
| IFN-α | 22.3 |
Functional Assessment of Cancer Therapy-General (FACT-G): Emotional Well Being (EWB) Subscale
Emotional well-being (EWB)subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 24; lower score indicates better emotional well-being. (NCT00083889)
Timeframe: Day 1 & 28 of each cycle: duration of treatment phase
| Intervention | scores on scale (Mean) |
|---|
| Baseline (370, 352) | Cycle 1 Day 28 (n=347, 318) | Cycle 2 Day 1 (n=328, 249) | Cycle 2 Day 28 (n=316, 237) | Cycle 3 Day 1 (n=294, 200) | Cycle 3 Day 28 (n=287, 196) | Cycle 4 Day 1 (n=272, 152) | Cycle 4 Day 28 (n=265, 142) | Cycle 5 Day 1 (n=249, 120) | Cycle 5 Day 28 (n=241, 109) | Cycle 6 Day 1 (n=240, 99) | Cycle 6 Day 28 (n=222, 99) | Cycle 7 Day 1 (n=208, 77) | Cycle 7 Day 28 (n=204, 75) | Cycle 8 Day 1 (n=192, 67) | Cycle 8 Day 28 (n=189, 62) | Cycle 9 Day 1 (n=171, 51) | Cycle 9 Day 28 (n=167, 46) | Cycle 10 Day 1 (n=161, 50) | Cycle 10 Day 28 (n=154, 45) | Cycle 11 Day 1 (n=138, 35) | Cycle 11 Day 28 (n=141, 33) | Cycle 12 Day 1 (n=132, 30) | Cycle 12 Day 28 (n=128, 31) | Cycle 13 Day 1 (n=114, 27) | Cycle 13 Day 28 (n=114, 27) | Cycle 14 Day 1 (n=114, 26) | Cycle 14 Day 28 (n=107, 25) | Cycle 15 Day 1 (n=101, 21) | Cycle 15 Day 28 (n=96, 20) | Cycle 16 Day 1 (n=96, 19) | Cycle 16 Day 28 (n=91, 18) | Cycle 17 Day 1 (n=84, 17) | Cycle 17 Day 28 (n=81, 14) | Cycle 18 Day 1 (n=80, 12) | Cycle 18 Day 28 (n=71, 11) | Cycle 19 Day 1 (n=71, 11) | Cycle 19 Day 28 (n=61, 10) | Cycle 20 Day 1 (n=65, 9) | Cycle 20 Day 28 (n=53, 9) |
|---|
| IFN-α | 17.06 | 17.40 | 17.52 | 17.73 | 18.13 | 18.17 | 18.80 | 18.39 | 19.00 | 18.70 | 18.60 | 18.14 | 18.08 | 18.55 | 18.54 | 18.55 | 18.98 | 18.76 | 18.92 | 18.36 | 18.97 | 18.52 | 18.87 | 19.45 | 18.63 | 18.97 | 18.05 | 18.76 | 18.24 | 18.75 | 17.26 | 16.83 | 18.28 | 18.00 | 19.62 | 19.55 | 19.09 | 18.20 | 18.67 | 18.67 |
,| SU011248 | 17.15 | 17.76 | 18.46 | 18.46 | 18.82 | 18.53 | 19.04 | 18.76 | 19.18 | 18.63 | 18.99 | 18.73 | 19.08 | 18.69 | 19.33 | 18.98 | 19.25 | 18.93 | 19.32 | 18.71 | 18.92 | 19.10 | 19.14 | 19.06 | 19.38 | 19.39 | 19.55 | 19.23 | 19.57 | 19.41 | 19.54 | 19.33 | 19.95 | 19.66 | 19.64 | 19.34 | 19.94 | 19.61 | 20.00 | 19.75 |
Functional Assessment of Cancer Therapy-General (FACT-G)
Functional Assessment of Cancer Therapy-General (FACT-G): core questionnaire of the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system that has been validated in a variety of cancer populations. 27 questions grouped into 4 domains that measure a patient's physical, functional, social and family, and emotional well-being. Five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = sum score of item scores in the subscale; total range: 0 to 108 with higher score indicating better quality of life. (NCT00083889)
Timeframe: Day 1 & 28 of each cycle: duration of treatment phase
| Intervention | scores on scale (Mean) |
|---|
| Baseline (n=368, 346) | Cycle 1 Day 28 (n=345, 316) | Cycle 2 Day 1 (n=328, 247) | Cycle 2 Day 28 (n=314, 237) | Cycle 3 Day 1 (n=293, 199) | Cycle 3 Day 28 (n=285, 193) | Cycle 4 Day 1 (n=269, 149) | Cycle 4 Day 28 (n=263, 142) | Cycle 5 Day 1 (n=247, 119) | Cycle 5 Day 28 (n=240, 106) | Cycle 6 Day 1 (n=238, 98) | Cycle 6 Day 28 (n=222, 97) | Cycle 7 Day 1 (n=206, 78) | Cycle 7 Day 28 (n=200, 75) | Cycle 8 Day 1 (n=192, 66) | Cycle 8 Day 28 (n=189, 61) | Cycle 9 Day 1 (n=170, 51) | Cycle 9 Day 28 (n=166, 46) | Cycle 10 Day 1 (n=158, 49) | Cycle 10 Day 28 (n=150, 45) | Cycle 11 Day 1 (n=134, 35) | Cycle 11 Day 28 (n=139, 32) | Cycle 12 Day 1 (n=130, 29) | Cycle 12 Day 28 (n=126, 31) | Cycle 13 Day 1 (n=113, 27) | Cycle 13 Day 28 (n=114, 27) | Cycle 14 Day 1 (n=112, 26) | Cycle 14 Day 28 (n=107, 24) | Cycle 15 Day 1 (n=101, 20) | Cycle 15 Day 28 (n=96, 20) | Cycle 16 Day 1 (n=94, 19) | Cycle 16 Day 28 (n=89, 18) | Cycle 17 Day 1 (n=84, 16) | Cycle 17 Day 28 (n=80, 14) | Cycle 18 Day 1 (n=79, 12) | Cycle 18 Day 28 (n=70, 11) | Cycle 19 Day 1 (n=71, 11) | Cycle 19 Day 28 (n=61, 10) | Cycle 20 Day 1 (n=63, 9) | Cycle 20 Day 28 (n=52, 8) |
|---|
| IFN-α | 81.22 | 74.91 | 77.02 | 77.05 | 79.35 | 78.42 | 80.86 | 80.46 | 81.96 | 80.60 | 81.97 | 79.70 | 80.39 | 81.06 | 81.25 | 81.31 | 84.50 | 83.14 | 84.03 | 81.79 | 81.60 | 80.20 | 80.99 | 81.73 | 81.18 | 80.67 | 81.22 | 81.57 | 81.66 | 80.88 | 78.20 | 78.38 | 81.80 | 78.96 | 82.24 | 82.27 | 82.48 | 79.63 | 81.70 | 79.54 |
,| SU011248 | 82.30 | 78.75 | 82.88 | 80.51 | 84.24 | 80.59 | 85.32 | 82.08 | 86.40 | 82.23 | 84.90 | 82.54 | 85.01 | 82.16 | 86.83 | 83.05 | 85.81 | 82.71 | 85.32 | 82.14 | 84.75 | 81.91 | 85.31 | 82.43 | 85.50 | 83.61 | 85.24 | 82.34 | 86.24 | 82.64 | 84.77 | 83.38 | 86.78 | 84.42 | 85.74 | 83.51 | 87.16 | 84.54 | 87.96 | 84.62 |
FACT-Kidney Symptom Index (FKSI) Subscale
FACT-Kidney Symptom Index (FKSI) subscale designed to be a stand-alone instrument to measure symptoms and quality of life in patients with advanced kidney cancer. Contains 15 questions; some questions overlap with the FACT-G questions. Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Total FKSI score = sum score of the 15 item scores; total range: 0 - 60; 0 (most severe symptoms and concerns) to 60 (no symptoms or concerns). (NCT00083889)
Timeframe: Day 1 & 28 of each cycle: duration of treatment phase
| Intervention | scores on scale (Mean) |
|---|
| Baseline (n=369, 351) | Cycle 1 Day 28 (n=348, 317) | Cycle 2 Day 1 (n=327, 246) | Cycle 2 Day 28 (n=315, 238) | Cycle 3 Day 1 (n=294, 198) | Cycle 3 Day 28 (n=285, 195) | Cycle 4 Day 1 (n=272, 151) | Cycle 4 Day 28 (n=264, 142) | Cycle 5 Day 1 (n=248, 119) | Cycle 5 Day 28 (n=242, 109) | Cycle 6 Day 1 (n=240, 99) | Cycle 6 Day 28 (n=223, 99) | Cycle 7 Day 1 (n=208, 79) | Cycle 7 Day 28 (n=203, 75) | Cycle 8 Day 1 (n=192, 68) | Cycle 8 Day 28 (n=190, 62) | Cycle 9 Day 1 (n=172, 51) | Cycle 9 Day 28 (n=166, 46) | Cycle 10 Day 1 (n=161, 50) | Cycle 10 Day 28 (n=155, 46) | Cycle 11 Day 1 (n=138, 35) | Cycle 11 Day 28 (n=141, 33) | Cycle 12 Day 1 (n=132, 31) | Cycle 12 Day 28 (n=128, 31) | Cycle 13 Day 1 (n=113, 27) | Cycle 13 Day 28 (n=114, 27) | Cycle 14 Day 1 (n=114, 26) | Cycle 14 Day 28 (n=105, 25) | Cycle 15 Day 1 (n=100, 22) | Cycle 15 Day 28 (n=94, 20) | Cycle 16 Day 1 (n=96, 19) | Cycle 16 Day 28 (n=90, 18) | Cycle 17 Day 1 (n=85, 17) | Cycle 17 Day 28 (n=81, 14) | Cycle 18 Day 1 (n=80, 12) | Cycle 18 Day 28 (n=70, 11) | Cycle 19 Day 1 (n=71, 11) | Cycle 19 Day 28 (n=61, 10) | Cycle 20 Day 1 (n=65, 9) | Cycle 20 Day 28 (n=53, 9) |
|---|
| IFN-α | 46.09 | 40.93 | 42.33 | 42.01 | 43.64 | 43.13 | 44.78 | 44.03 | 44.82 | 44.41 | 45.38 | 44.07 | 45.09 | 44.65 | 45.38 | 45.10 | 46.88 | 46.16 | 46.22 | 45.16 | 46.26 | 45.46 | 46.08 | 46.00 | 46.25 | 45.84 | 46.08 | 46.10 | 45.62 | 45.30 | 43.64 | 43.46 | 45.59 | 43.64 | 44.92 | 45.27 | 46.64 | 44.47 | 45.00 | 46.00 |
,| SU011248 | 46.45 | 42.71 | 45.98 | 43.75 | 46.60 | 44.01 | 46.99 | 45.08 | 47.99 | 44.99 | 47.61 | 45.40 | 47.84 | 45.39 | 48.24 | 45.83 | 48.31 | 45.79 | 47.90 | 45.70 | 47.90 | 45.28 | 47.90 | 45.67 | 48.02 | 45.65 | 47.90 | 45.10 | 48.26 | 45.37 | 47.75 | 45.95 | 48.07 | 46.27 | 47.47 | 45.36 | 47.70 | 46.07 | 48.88 | 46.26 |
EuroQoL Five Dimension (EQ-5D) Health State Index
EQ-5D Health State Index: a brief, self-administered generic health status instrument. Respondents were asked to describe their current health state on each of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety or depression) on a three-level scale (1=no problem, 2=some problem, and 3=extreme problem). A maximum score of 1 can be derived from these 5 dimensions by score conversion; range: -0.39 (worst health state)to 1.00 (best health state). This descriptive system classifies respondents into one of 243 possible distinct health states (EQ-5D descriptive system). (NCT00083889)
Timeframe: Day 1 & 28 of each cycle: duration of treatment phase
| Intervention | scores on scale (Mean) |
|---|
| Baseline (n=363, 352) | Cycle 1 Day 28 (346, 315) | Cycle 2 Day 1 (326, 244) | Cycle 2 Day 28 (311, 233) | Cycle 3 Day 1 (287, 200) | Cycle 3 Day 28 (283, 195) | Cycle 4 Day 1 (269, 150) | Cycle 4 Day 28 (261, 142) | Cycle 5 Day 1 (247, 120) | Cycle 5 Day 28 (240, 106) | Cycle 6 Day 1 (240, 98) | Cycle 6 Day 28 (224, 100) | Cycle 7 Day 1 (205, 79) | Cycle 7 Day 28 (204, 74) | Cycle 8 Day 1 (192, 68) | Cycle 8 Day 28 (190, 61) | Cycle 9 Day 1 (170, 51) | Cycle 9 Day 28 (168, 45) | Cycle 10 Day 1 (161, 50) | Cycle 10 Day 28 (153, 46) | Cycle 11 Day 1 (138, 34) | Cycle 11 Day 28 (138, 32) | Cycle 12 Day 1 (132, 31) | Cycle 12 Day 28 (127, 31) | Cycle 13 Day 1 (114, 26) | Cycle 13 Day 28 (115, 27) | Cycle 14 Day 1 (114, 25) | Cycle 14 Day 28 (107, 24) | Cycle 15 Day 1 (100, 21) | Cycle 15 Day 28 (95, 20) | Cycle 16 Day 1 (96, 19) | Cycle 16 Day 28 (93, 18) | Cycle 17 Day 1 (84, 15) | Cycle 17 Day 28 (82, 14) | Cycle 18 Day 1 (80, 12) | Cycle 18 Day 28 (71, 10) | Cycle 19 Day 1 (69, 11) | Cycle 19 Day 28 (62, 11) | Cycle 20 Day 1 (63, 8) | Cycle 20 Day 28 (54, 9) |
|---|
| IFN-α | 0.76 | 0.70 | 0.75 | 0.74 | 0.76 | 0.75 | 0.80 | 0.79 | 0.79 | 0.78 | 0.80 | 0.80 | 0.80 | 0.81 | 0.82 | 0.81 | 0.84 | 0.84 | 0.85 | 0.82 | 0.85 | 0.84 | 0.82 | 0.85 | 0.83 | 0.82 | 0.86 | 0.87 | 0.88 | 0.88 | 0.84 | 0.83 | 0.88 | 0.83 | 0.86 | 0.84 | 0.88 | 0.72 | 0.85 | 0.86 |
,| SU011248 | 0.76 | 0.72 | 0.78 | 0.73 | 0.78 | 0.75 | 0.80 | 0.76 | 0.80 | 0.76 | 0.80 | 0.77 | 0.81 | 0.77 | 0.82 | 0.77 | 0.80 | 0.78 | 0.81 | 0.78 | 0.80 | 0.75 | 0.81 | 0.77 | 0.81 | 0.77 | 0.81 | 0.75 | 0.80 | 0.75 | 0.79 | 0.76 | 0.79 | 0.77 | 0.81 | 0.76 | 0.81 | 0.78 | 0.81 | 0.77 |
Euro-QoL Visual Analog Scale (EQ-VAS)
EQ-VAS: overall self-rating rating of the patient's current health state using a 20 cm Visual Analog Scale (EQ-VAS), also called the health state thermometer) is a metric measurement (in 2 mm interval) from the visual analog scale which ranges between 0 (worse imaginable health state) and 100 (best imaginable health state). (NCT00083889)
Timeframe: Day 1 & 28 of each cycle: duration of treatment phase
| Intervention | scores on scale (Mean) |
|---|
| Baseline (n=365, 352) | Cycle 1 Day 28 (n=347, 315) | Cycle 2 Day 1 (n=323, 247) | Cycle 2 Day 28 (n=314, 237) | Cycle 3 Day 1 (n=293, 198) | Cycle 3 Day 28 (n=287, 193) | Cycle 4 Day 1 (n=270, 152) | Cycle 4 Day 28 (n=264, 139) | Cycle 5 Day 1 (n=248, 118) | Cycle 5 Day 28 (n=240, 104) | Cycle 6 Day 1 (n=237, 99) | Cycle 6 Day 28 (n=223, 98) | Cycle 7 Day 1 (n=209, 77) | Cycle 7 Day 28 (n=201, 74) | Cycle 8 Day 1 (n=192, 67) | Cycle 8 Day 28 (n=191, 60) | Cycle 9 Day 1 (n=172, 50) | Cycle 9 Day 28 (n=168, 46) | Cycle 10 Day 1 (n=160, 50) | Cycle 10 Day 28 (n=154, 45) | Cycle 11 Day 1 (n=138, 34) | Cycle 11 Day 28 (n=141, 33) | Cycle 12 Day 1 (n=130, 31) | Cycle 12 Day 28 (n=128, 31) | Cycle 13 Day 1 (n=114, 27) | Cycle 13 Day 28 (n=115, 27) | Cycle 14 Day 1 (n=114, 26) | Cycle 14 Day 28 (n=107, 25) | Cycle 15 Day 1 (n=101, 21) | Cycle 15 Day 28 (n=96, 20) | Cycle 16 Day 1 (n=96, 19) | Cycle 16 Day 28 (n=92, 18) | Cycle 17 Day 1 (n=84, 17) | Cycle 17 Day 28 (n=82, 14) | Cycle 18 Day 1 (n=78, 12) | Cycle 18 Day 28 (n=70, 11) | Cycle 19 Day 1 (n=70, 11) | Cycle 19 Day 28 (n=62, 11) | Cycle 20 Day 1 (n=65, 9) | Cycle 20 Day 28 (n=54, 9) |
|---|
| IFN-α | 71.43 | 67.66 | 70.45 | 70.70 | 72.68 | 71.45 | 72.74 | 72.20 | 73.44 | 72.57 | 73.68 | 72.26 | 73.80 | 73.46 | 74.27 | 74.33 | 77.66 | 76.57 | 76.64 | 76.69 | 75.06 | 72.21 | 75.19 | 73.84 | 77.52 | 73.56 | 76.69 | 76.44 | 76.62 | 76.50 | 74.84 | 73.11 | 76.94 | 72.86 | 74.42 | 73.82 | 79.27 | 68.55 | 76.00 | 75.44 |
,| SU011248 | 73.80 | 69.35 | 75.05 | 72.06 | 76.23 | 72.33 | 77.46 | 75.15 | 79.83 | 75.13 | 78.83 | 76.81 | 79.39 | 76.09 | 81.34 | 77.53 | 80.08 | 76.24 | 79.18 | 76.44 | 79.72 | 76.81 | 80.84 | 76.71 | 80.59 | 77.22 | 80.39 | 76.53 | 80.50 | 76.51 | 79.85 | 75.51 | 80.74 | 77.10 | 80.40 | 77.76 | 81.47 | 77.05 | 81.10 | 76.85 |
Ctrough Concentrations of SU011248
Subject observed Ctrough (trough drug) concentrations of SU011248 per cycle and study day determined by plasma trough samples collected from a subset of patients. Steady-state observed trough concentrations were dose corrected to the starting dose (reference dose) where appropriate. Concentrations below the limits of quantitation (BLQ) were set to 0. Ctrough = minimum (trough) plasma concentration (nanograms per milliliter [ng/mL]). (NCT00083889)
Timeframe: Day 28 of Cycle 1 to Cycle 4
| Intervention | ng/mL (Mean) |
|---|
| Cycle 1, Day 28 (n=31) | Cycle 2, Day 28 (n=36) | Cycle 3, Day 28 (n=36) | Cycle 4, Day 28 (n=32) | Dose-Corrected: Cycle 1, Day 28 (n=24) | Dose-Corrected: Cycle 2, Day 28 (n=28) | Dose-Corrected: Cycle 3, Day 28 (n=27) | Dose-Corrected: Cycle 4, Day 28 (n=26) |
|---|
| SU011248 | 57.26 | 57.59 | 50.26 | 45.05 | 64.22 | 59.90 | 58.45 | 54.31 |
Plasma Concentrations of Soluble Proteins: Plasma VEGF-A, Plasma VEGF-C, Plasma sVEGFR-3, PLASMA IL-8, and PLASMA bFGF That May be Associated With Tumor Proliferation or Angiogenesis
Plasma concentrations of soluble proteins that may be associated with tumor proliferation or angiogenesis collected from a subset of patients were analyzed by enzyme-linked immunosorbent assay (ELISA) analysis. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio = plasma concentration of soluble protein (picograms per milliliter [pg/ml]) at timepoint / concentration of soluble protein (pg/ml) at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded. (NCT00083889)
Timeframe: Day 1 & Day 28, Cycle 1 to Cycle 4
| Intervention | pg/ml and ratio to Baseline (Mean) |
|---|
| Plasma VEGF-A: Baseline (n=33, 31) | Plasma VEGF-A: C1D28: C1D1 (n=31, 26) | Plasma VEGF-A: C2D1: C1D1 (n=32, 21) | Plasma VEGF-A: C2D28: C1D1 (n=31, 20) | Plasma VEGF-A: C3D1: C1D1 (n=27, 15) | Plasma VEGF-A: C3D28: C1D1 (n=28, 15) | Plasma VEGF-A: C4D1: C1D1 (n=27, 12) | Plasma VEGF-A: C4D28: C1D1 (n=25, 11) | Plasma VEGF-C: Baseline (n=35, 31) | Plasma VEGF-C: C1D28: C1D1 (n=31, 26) | Plasma VEGF-C: C2D1:C1D1 (n=30, 21) | Plasma VEGF-C: C2D28:C1D1 (n=31, 19) | Plasma VEGF-C: C3D1:C1D1 (n=28, 15) | Plasma VEGF-C: C3D28:C1D1 (n=28, 15) | Plasma VEGF-C: C4D1:C1D1 (n=28, 12) | Plasma VEGF-C: C4:D28:C1D1 (n=26, 11) | PLASMA sVEGFR-3: Baseline (n=29, 30) | PLASMA sVEGFR-3: C1D28:C1D1 (n=27, 25) | PLASMA sVEGFR-3: C2D1:C1D1 (n=28, 20) | PLASMA sVEGFR-3: C2D28:C1D1 (n=28, 19) | PLASMA sVEGFR-3: C3D1:C1D1 (n=25, 14) | PLASMA sVEGFR-3: C3D28:C1D1 (n=25, 14) | PLASMA sVEGFR-3: C4D1:C1D1 (n=24, 11) | PLASMA sVEGFR-3: C4:D28:C1D1 (n=23, 10) | PLASMA IL-8: Baseline (n=31, 29) | PLASMA IL-8: C1D28:C1D1 (n=29, 25) | PLASMA IL-8: C2D1:C1D1 (n=29, 20) | PLASMA IL-8: C2D28:C1D1 (n=29, 19) | PLASMA IL-8: C3D1:C1D1 (n=26, 15) | PLASMA IL-8: C3D28:C1D1 (n=26, 14) | PLASMA IL-8: C4D1:C1D1 (n=26, 12) | PLASMA IL-8: C4:D28:C1D1 (n=25, 11) | PLASMA bFGF: Baseline (n=21, 2) | PLASMA bFGF: C1D28:C1D1 (n=15, 1) | PLASMA bFGF: C2D1:C1D1 (n=13, 1) |
|---|
| IFN-α | 109.0 | 1.134 | 1.171 | 1.153 | 1.253 | 1.149 | 1.209 | 1.008 | 651.2 | 1.165 | 1.177 | 1.081 | 1.174 | 1.054 | 1.382 | 1.139 | 40317.7 | 1.068 | 1.075 | 1.150 | 1.015 | 1.042 | 1.183 | 1.044 | 18.6 | 2.297 | 1.579 | 1.858 | 1.531 | 1.999 | 1.662 | 2.492 | 13.6 | 0.429 | 0.157 |
,| SU011248 | 101.9 | 4.280 | 1.161 | 5.851 | 1.630 | 5.236 | 1.486 | 4.924 | 556.4 | 0.945 | 1.045 | 0.871 | 1.159 | 1.043 | 1.243 | 1.207 | 44049.3 | 0.473 | 0.787 | 0.407 | 0.800 | 0.427 | 0.846 | 0.486 | 10.1 | 2.815 | 1.716 | 2.423 | 2.788 | 2.574 | 1.934 | 2.549 | 13.1 | 2.762 | 1.370 |
Time to Tumor Progression (TTP), Core Radiology Assessment
TTP = time from randomization to first documentation of objective tumor progression. TTP data were censored on the day following the date of last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects who did not have objective tumor progression while on treatment or who were given anti-tumor treatment other than study treatment prior to documentation of objective tumor progression. Subjects with no tumor assessments after randomization had TTP censored on the date of randomization with a duration of 1 day. (NCT00083889)
Timeframe: Randomization to first documentation of tumor progression: duration of treatment phase
| Intervention | weeks (Median) |
|---|
| SU011248 | 49.1 |
| IFN-α | 22.4 |
Duration of Response (DR), Core Radiology Assessement
Duration of response (DR) = time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause. DR data were censored on the day following the date of the last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects without objective tumor progression who did not die due to any cause while on treatment or who were given anti-tumor treatment other than study treatment prior to observing tumor progression. (NCT00083889)
Timeframe: Day 28 of each cycle: duraton of treatment phase
| Intervention | weeks (Median) |
|---|
| SU011248 | 52.9 |
| IFN-α | 64.9 |
Duration of Response (DR), Investigator's Assessment
Duration of response (DR) = time from the first documentation of objective tumor response to the first documentaion of objective tumor progression or to death due to any cause. DR data were censored on the day following the date of the last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects without objective tumor progression who did not die due to any cause while on treatment or who were given anti-tumor treatment other than study treatment prior to observing tumor progression. (NCT00083889)
Timeframe: Day 28 of each cycle: duration of treatment phase
| Intervention | weeks (Median) |
|---|
| SU011248 | 56.3 |
| IFN-α | 48.1 |
Incremental Cost Effectiveness Ratio (ICER)
Incremental cost effectiveness ratio (ICER) of sunitinib compared to IFN-a as first-line treatment for MRCC, defined as the ratio of the incremental cost of treatment over the incremental effectiveness; effectiveness measured as quality adjusted life year (QALY) gain. This objective was not addressed in the clinical study report, but an interim analysis of cost-effectiveness was presented separately. These results were not available for inclusion at the time of this posting. (NCT00083889)
Timeframe: post study measurement
| Intervention | ratio (Number) |
|---|
| SU011248 | 0 |
| IFN-α | 0 |
Objective Response, Core Radiology Assessment
Objective response (OR) = the number of patients with confirmed complete response (CR) and confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, relative to all randomized patients. CR was defined as the disappearance of all target lesions. PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Confirmed responses (CR or PR) = those that persisted on repeat imaging study >= 4 weeks after initial documentation of response. (NCT00083889)
Timeframe: Day 28 of each 6-week cycle: duration of treatment phase
| Intervention | participants (Number) |
|---|
| SU011248 | 145 |
| IFN-α | 29 |
Objective Response, Investigator's Assessment
Objective response (OR) = the number of patients with confirmed complete response (CR) and confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, relative to all randomized patients. CR was defined as the disappearance of all target lesions. PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Confirmed responses = those that persist on repeat imaging study >= 4 weeks after initial documentation of response. (NCT00083889)
Timeframe: Day 28 of each 6-week cycle: duration of treatment phase
| Intervention | participants (Number) |
|---|
| SU011248 | 171 |
| IFN-α | 45 |
Overall Survival (OS)
Overall survival (OS) = time from date of randomization to date of death due to any cause. For patients not expiring, survival time was censored at the last date they were known to be alive. Patients lacking data beyond randomization had their survival times censored at the date of randomization with a duration of 1 day. (NCT00083889)
Timeframe: Clinic visit or telephone contact every 2 months until death
| Intervention | weeks (Median) |
|---|
| SU011248 | 114.6 |
| IFN-α | 94.9 |
Progression-Free Survival (PFS), Core Radiology Assessment
Progression-free survival (PFS) = time from randomization to first documentation of objective tumor progression or to death due to any cause, whichever occured first. If tumor progression data included more than 1 date, the first date was used. PFS = first event date minus the date of randomization + 1. On study included treatment plus 28-day follow-up periods. (NCT00083889)
Timeframe: Day 28 of each 6-week cycle: duration of treatment phase
| Intervention | weeks (Median) |
|---|
| SU011248 | 48.3 |
| IFN-α | 22.1 |
Progression-Free Survival (PFS), Investigator's Assessment
Progression-free survival = time from randomization to first documentation of objective tumor progression or to death due to any cause, whichever occured first. PFS = first event date minus the date of randomization + 1). On study included treatment plus 28-day follow-up periods. (NCT00083889)
Timeframe: Day 28 of each 6-week cycle: duration of treatment phase
| Intervention | weeks (Median) |
|---|
| SU011248 | 47.7 |
| IFN-α | 22.1 |
Clinical Response as Measured by RECIST
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00085436)
Timeframe: monthly, then every 2-3 months
| Intervention | percentage of participants (Number) |
|---|
| Treatment | 50 |
Immunity as Measured by T-cell and Antibody Responses to the Tumor
All patients receiving at least one week of treatment and have at least two time points available for assessment of immune parameters will be include in the evaluation of immune status. (NCT00085436)
Timeframe: monthly for 5 months
| Intervention | pg/mL (picogram/milliliter) (Number) |
|---|
| IP-10 Pre treatment | IP-10 Post treatment |
|---|
| Vaccine, Aldesleukin-2, Interferon-a | 126 | 521 |
Number of Participants With Sustained Virologic Response (SVR)
SVR [ Sustained virological response] SVR was defined as HCV RNA levels below the limit of detection 24 weeks after the end of treatment. (NCT00085917)
Timeframe: 72 weeks
| Intervention | participants (Number) |
|---|
| Pegasys Single Dose | 11 |
| Pegasys Double Dose | 11 |
Number of Participants With Normalization of Liver Enzymes
normalization of liver enzymes :Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) Alanine aminotransferase (ALT): Normal 6 - 41 U/L Aspartate aminotransferase (AST) : Normal 9 - 34 U/L (NCT00085917)
Timeframe: week 24, week 48, week 72
| Intervention | participants (Number) |
|---|
| Pegasys Single Dose | 11 |
| Pegasys Double Dose | 11 |
Number of Participants With Adverse Events
"Adverse Events~- Anemia, Neutropenia and Psychiatric adverse events" (NCT00085917)
Timeframe: 48 weeks
| Intervention | participants (Number) |
|---|
| Pegasys Single Dose | 11 |
| Pegasys Double Dose | 11 |
Adverse Events
Influenza-like, headache, and gastrointestinal symptoms (NCT00100659)
Timeframe: At any time up to 72 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Influenza-like symptoms | Headache | Gastrointestinal symptoms |
|---|
| Pegylated Interferon/Placebo | 50 | 30 | 37 |
,| Pegylated Interferon/Ribavirin | 50 | 34 | 31 |
Sustained Viral Response (SVR)
SVR is defined as nondetectable hepatitis C virus ribonucleic acid (HCV RNA) in plasma (NCT00100659)
Timeframe: at least 24 weeks after stopping treatment.
| Intervention | participants (Number) |
|---|
| PEG/RV | 29 |
| PEG/Placebo | 12 |
Number of Participants Who Were Neutralising Antibody (NAb) Positive at Anytime During the Study
The NAb positive value was defined as NAb value greater or equal to 20 NU/mL. NAbs were detected using a viral cytopathic assay. (NCT00110396)
Timeframe: 96 weeks
| Intervention | participants (Number) |
|---|
| Rebif New Formulation (RNF) Cohort | 49 |
Number of Participants With Binding Antibodies (BAb) at Week 96
Presence of BAbs. BAbs were measured by ELISA (Enzyme-linked immunosorbent assay). (NCT00110396)
Timeframe: 96 weeks
| Intervention | Participants (Number) |
|---|
| Rebif New Formulation (RNF) Cohort | 74 |
Number of Participants Who Were Neutralising Antibody (NAb) Positive at the Week 96 Visit.
The NAb positive value was defined as NAb value greater or equal to 20 NU/mL. NAbs were detected using a viral cytopathic assay. (NCT00110396)
Timeframe: 96 weeks
| Intervention | participants (Number) |
|---|
| Rebif New Formulation (RNF) Cohort | 45 |
Average of All Trough Plasma Concentrations
Plasma samples were collected prior to dosing every 4 weeks after the patient reached steady-state (at least 10 days at 400 mg BID). (NCT00117637)
Timeframe: From start of treatment of the first subject until 15 months later assessed every 4 weeks.
| Intervention | 100*mg/L (Geometric Mean) |
|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600mg | 93.9 |
Duration of Response According to the Independent Radiological Review for the First Intervention Period
Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | months (Median) |
|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 7.5 |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 7.7 |
Duration of Response According to the Investigator Assessment for the First Intervention Period
Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Intervention | months (Median) |
|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 4.4 |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 9.2 |
Duration of Response According to the Investigator Assessment for the Second Intervention Period
Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Intervention | months (Median) |
|---|
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 5.5 |
Overall Survival (OS)
Overall Survival was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Intervention | months (Median) |
|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 14.8 |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 26.9 |
Progression Free Survival According to the Investigator Assessment (Second Intervention Period)
Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Intervention | months (Median) |
|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 4.5 |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 5.5 |
Progression-free Survival (PFS) Based on Independent Radiological Review for the First Intervention Period
Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | months (Median) |
|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 5.7 |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 5.6 |
Progression-free Survival (PFS) Based on Investigator Assessment for the First Intervention Period
Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Intervention | months (Median) |
|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 5.6 |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 7.0 |
Slope - Change in Trough Concentration/Cycle
Plasma samples were collected prior to dosing every 4 weeks after the patient reached steady-state (at least 10 days at 400 mg BID (bis in die, twice daily)) to assess any potential trends in trough concentration over time. (NCT00117637)
Timeframe: From start of treatment of the first subject until 15 months later assessed every 4 weeks.
| Intervention | 100*(mg/L/cycle) (Mean) |
|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600mg | -8.3 |
Time to Response According to the Investigator Assessment for the First Intervention Period
Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation was defined as the time from date of randomization to the earliest date that the response was first documented (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
| Intervention | months (Median) |
|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 3.5 |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 5.4 |
Time to Response According to the Investigator Assessment for the Second Intervention Period
Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation) was defined as the time from date of randomization to the earliest date that the response was first documented (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
| Intervention | months (Median) |
|---|
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 1.7 |
Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period
Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst). (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
| Intervention | participants (Number) |
|---|
| 0= Fully active without restriction | 1= Restricted in physically strenuous activity | 2= Ambulatory, capable of all selfcare | 3= Capable of limited selfcare | 4= Completely disabled | 5= Dead |
|---|
| Interferon Therapy in Period 1 | 19 | 42 | 21 | 5 | 2 | 0 |
,| Sorafenib 400 mg in Period 1 | 20 | 48 | 20 | 5 | 1 | 1 |
Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period
Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst). (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
| Intervention | participant s (Number) |
|---|
| 0= Fully active without restriction | 1= Restricted in physically strenuous activity | 2= Ambulatory, capable of all selfcare | 3= Capable of limited selfcare | 4= Completely disabled | 5= Dead |
|---|
| Sorafenib 400 mg (After Interferon Therapy) | 16 | 26 | 10 | 5 | 1 | 0 |
,| Sorafenib 600 mg (as Dose Escalation After 400 mg) | 5 | 25 | 10 | 4 | 1 | 0 |
Disease Control (DC) According to Independent Central Review for the First Intervention Period
Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | participants (Number) |
|---|
| disease control (CR or PR or SD) | no disease control | Unknown |
|---|
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 59 | 24 | 9 |
,| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 77 | 10 | 10 |
Disease Control (DC) According to the Investigator Assessment for the First Intervention Period
Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes. (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Intervention | participants (Number) |
|---|
| disease control (CR or PR or SD) | no disease control | Unknown |
|---|
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 62 | 24 | 6 |
,| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 83 | 7 | 7 |
Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period
Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes. (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Intervention | participants (Number) |
|---|
| disease control (CR or PR or SD) | no disease control | Unknown |
|---|
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 49 | 6 | 6 |
,| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 25 | 16 | 8 |
Tumor Response According to the Independent Radiological Review for the First Intervention Period
Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Not Evaluated |
|---|
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 1 | 7 | 51 | 24 | 9 |
,| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 0 | 5 | 72 | 10 | 10 |
Tumor Response According to the Investigator Assessment for the First Intervention Period
Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Not Evaluated |
|---|
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 1 | 13 | 48 | 24 | 6 |
,| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 0 | 21 | 62 | 7 | 7 |
Tumor Response According to the Investigator Assessment for the Second Intervention Period
Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes (NCT00117637)
Timeframe: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Not Evaluated |
|---|
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 1 | 11 | 37 | 6 | 6 |
,| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 0 | 0 | 25 | 16 | 8 |
Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the First Intervention Period
The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 400 mg in Period 1 | 40.5 |
| Interferon Therapy in Period 1 | 34.6 |
Time to Response According to the Independent Radiological Review for the First Intervention Period
Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation was defined as the time from date of randomization to the earliest date that the response was first documented (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | months (Median) |
|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | 1.8 |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | 5.4 |
Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the First Intervention Period
The FACT-BRM comprises 40 questions within 6 domains (physical well being, social/family well being, emotional well being, additional concern: physical, and additional concern: emotional). Each question was answered on a five point scale from 0 (not at all) to 4 (very much). The total score range is from 0 to 160 with higher scores indicating better QoL. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 400 mg in Period 1 | 104 |
| Interferon Therapy in Period 1 | 93 |
Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the Second Intervention Period
The FACT-BRM comprises 40 questions within 6 domains (physical well being, social/family well being, emotional well being, additional concern: physical, and additional concern: emotional). Each question was answered on a five point scale from 0 (not at all) to 4 (very much). The total score range is from 0 to 160 with higher scores indicating better QoL. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 600 mg (as Dose Escalation After 400 mg) | 89.7 |
| Sorafenib 400 mg (After Interferon Therapy) | 108.4 |
Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) After Intervention for the First Intervention Period
"The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. The respiratory domain of the FKSI comprises 2 questions: I have been short in breath and I have been coughing; its score ranges from 0 to 8." (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 400 mg in Period 1 | 6.4 |
| Interferon Therapy in Period 1 | 5.1 |
Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period
"The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. The respiratory domain of the FKSI comprises 2 questions: I have been short in breath and I have been coughing; its score ranges from 0 to 8." (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 600 mg (as Dose Escalation After 400 mg) | 5.7 |
| Sorafenib 400 mg (After Interferon Therapy) | 6.4 |
Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period
The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 600 mg (as Dose Escalation After 400 mg) | 34.6 |
| Sorafenib 400 mg (After Interferon Therapy) | 42.3 |
Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 400 mg in Period 1 | 82 |
| Interferon Therapy in Period 1 | 66 |
Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 600 mg (as Dose Escalation After 400 mg) | 86.5 |
| Sorafenib 400 mg (After Interferon Therapy) | 82.5 |
Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 400 mg in Period 1 | 52 |
| Interferon Therapy in Period 1 | 42 |
Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 600 mg (as Dose Escalation After 400 mg) | 56.9 |
| Sorafenib 400 mg (After Interferon Therapy) | 40.3 |
Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 400 mg in Period 1 | 60 |
| Interferon Therapy in Period 1 | 46 |
Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 400 mg in Period 1 | 63 |
| Interferon Therapy in Period 1 | 46 |
Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 600 mg (as Dose Escalation After 400 mg) | 61.3 |
| Sorafenib 400 mg (After Interferon Therapy) | 57.6 |
Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. (NCT00117637)
Timeframe: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Sorafenib 600 mg (as Dose Escalation After 400 mg) | 39.9 |
| Sorafenib 400 mg (After Interferon Therapy) | 35.4 |
Duration of Response for Participants With Stable Disease (N=37) Following Treatment
Duration of response for participants with disease stabilization following treatment as measured from the date response is confirmed to the date of disease progression, first assessed up to 8 weeks (2 cycles) following start of treatment. The duration of a Stable Disease (SD) response is measured from the time measurement criteria are met for that specific SD response until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Repeat radiologic studies (CT, MRI, Chest x-ray and bone scan as indicated) to evaluate disease progression or response every 8 weeks. (NCT00126594)
Timeframe: From the date response is confirmed to the date of disease progression, up to 12 months
| Intervention | Months (Median) |
|---|
| Sorafenib Tosylate or Sorafenib Plus Interferon | 5.7 |
Objective Response Rate (ORR) Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST)
ORR defined as participants with Complete Response (CR) and Partial Response (PR) as defined by RECIST criteria: Complete Response (CR): Disappearance all target lesions. Partial Response (PR): >30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD. Progressive Disease (PD): >20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started. Radiologic testing for progressive disease repeated every 8 weeks. (NCT00126594)
Timeframe: Tumor restaging performed at 8 weeks following baseline, responding or stable participants restaged at 8 week intervals, up to 12 months.
| Intervention | percentage of participants (Number) |
|---|
| Sorafenib Tosylate | 30 |
| Sorafenib Tosylate, Recombinant Interferon Alfa-2b | 25 |
Progression-free Survival
Progression free survival (PFS) is defined as the time interval from the start of protocol therapy to death or disease progression. (NCT00126594)
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
| Intervention | Months (Median) |
|---|
| Sorafenib Tosylate | 7.39 |
| Sorafenib Tosylate, Recombinant Interferon Alfa-2b | 7.56 |
Best Overall Response for Participants
Best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The participant's best response assignment will depend on the achievement of both measurement and confirmation criteria as defined by RECIST: Complete Response (CR): Disappearance all target lesions. Partial Response (PR): >30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD. Progressive Disease (PD): >20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started. Radiologic testing for progressive disease repeated every 8 weeks. (NCT00126594)
Timeframe: From the date response is confirmed to the date of disease progression, first assessed 2 months (8 weeks) following start of treatment and reassessed up to 36 months (on average reassessed 12 months or less).
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Inevaluable |
|---|
| Sorafenib Tosylate | 1 | 11 | 17 | 6 | 5 |
,| Sorafenib Tosylate, Recombinant Interferon Alfa-2b | 0 | 10 | 20 | 7 | 3 |
Selected Grade 3-4 Adverse Events Using NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Adverse events graded using the CTCAE version 4.0 tabulated by treatment arm within either toxicity grade for the treatment period. Treatment-related toxicity (acute and cumulative) performed every 8 weeks during the first year. (NCT00126594)
Timeframe: Up to 12 months of treatment
| Intervention | participants (Number) |
|---|
| Fatigue | Diarrhea | Hand-Foot Syndrome | Hyperuricemia | Hyperamylasemia or Lipasemia | Dyspnea | Hypophosphatemia | Neutropenia | Hypertension | Nausea and vomiting | Rash/Desquamation | Proteinuria | Syncope (Fainting) | Weight Loss | Transaminitis | Hyponatremia | Nonneutropenic Infection | Sensory Neuropathy | Cardiac Ischemia/Infarction | Appendicitis | Pancreatitis | Adrenal Insufficiency | Reversible Posterior Leukonencephalopathy | Small Bowel Obstruction | Pneumonitis |
|---|
| Sorafenib Tosylate | 10 | 13 | 10 | 12 | 5 | 4 | 3 | 0 | 2 | 1 | 2 | 1 | 0 | 0 | 0 | 2 | 2 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 |
,| Sorafenib Tosylate, Recombinant Interferon Alfa-2b | 13 | 8 | 7 | 3 | 4 | 4 | 5 | 6 | 3 | 3 | 2 | 2 | 3 | 3 | 3 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
Percentage of Patients With Overall Survival
"Overall survival is time from randomization until death from any cause.~Will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals. Participants will be assessed for up to 10 years. 5 year overall survival is provided as a summary." (NCT00134030)
Timeframe: From date of randomization to date of death.
| Intervention | Percentage of participants (Number) |
|---|
| MAP-GR | 84 |
| MAPifn | 84 |
| MAP-PR | 68 |
| MAPIE | 68 |
Event-free Survival (EFS)
"EFS is defined as time from randomisation to the first of: death, detection of local recurrence or metastasis, progression of metastatic disease, or detection of a secondary malignancy.~EFS will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals. Follow up per participant will be assessed for up to 10 years. The 3 year EFS is provided as a summary." (NCT00134030)
Timeframe: From date of randomization to date of the event.
| Intervention | Percentage EFS (Number) |
|---|
| MAP-GR | 74 |
| MAPifn | 77 |
| MAP-PR | 55 |
| MAPIE | 53 |
Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Percentages of patients experiencing grade 3 and 4 adverse events. These will be compared using chi-square tests or Fisher's exact tests where appropriate. (NCT00134030)
Timeframe: Adverse events are assessed for up to 10 years per participant.
| Intervention | Participants (Count of Participants) |
|---|
| MAP-GR | 348 |
| MAPifn | 340 |
| MAP-PR | 287 |
| MAPIE | 281 |
Determination of the Effect of PEG-Intron 0.5mg Per kg Weekly sc Versus Colchicine 0.6mg Bid Daily on:
number of patients with a liver related outcomes including: mortality, liver transplant, variceal or portal hypertensive bleeding,Development of jaundice, ascites or encephalopathy with an increase in CPT of > 2 points and development of hepatoma (NCT00179413)
Timeframe: 4 years
| Intervention | Participants (Count of Participants) |
|---|
| PEG-Intron | 53 |
| Colchicine | 59 |
Development of Portal Hypertension
Number of patients who develop endoscopic evidence of varices over 4 year period (NCT00179413)
Timeframe: 4 years
| Intervention | Participants (Count of Participants) |
|---|
| PEG-Intron | 12 |
| Colchicine | 24 |
Evaluation of Safety and Tolerability of Long Term Maintenance PEG-Intron in Patients With Cirrhosis
Defined as the number of patients who discontinued therapy due to an adverse event side (NCT00179413)
Timeframe: 4 years
| Intervention | Participants (Count of Participants) |
|---|
| PEG-Intron | 38 |
| Colchicine | 20 |
Annualized Relapse Rate
annualized # of relapses between years 0 and 10 (NCT00179478)
Timeframe: 10 years
| Intervention | annualized relapses per year (Mean) |
|---|
| Immediate Treatment Group | 0.16 |
| Delayed Treatment Group | 0.33 |
Rate of Development of Clinical Definite Multiple Sclerosis (CDMS) Over 10 Years
Percent cumulative probability of developing CDMS over 10 years . CDMS was defined as the development of new visual or neurological symptoms discrete from the patients initial event with objective findings on examination. (NCT00179478)
Timeframe: 10 years
| Intervention | Percent cumulative probability (Number) |
|---|
| Immediate Treatment Group | 58 |
| Delayed Treatment Group | 69 |
The Number of New or Enlarging MRI T2 Lesions at 10 Years
These are counts of new or significantly enlarged lesions over 10 years on brain MRI reflecting interval radiographic disease activity (NCT00179478)
Timeframe: 10 years
| Intervention | # of new or enlarging T2 lesions (Median) |
|---|
| Immediate Treatment Group | 5 |
| Delayed Treatment Group | 7 |
Number of Participants With an EDSS > 3.5 at Study Completion
The EDSS is an ordinal scale of neurological impairment in Multiple Sclerosis with a range of 0 to 10 with 0.5 increments. A score of 0 is normal and 10 is death from MS. Scores from 1 to 3.5 are considered mild impairment , 4.0 to 6.5 is moderate and greater than 6.5 is severe impairment. (NCT00179478)
Timeframe: 10 years
| Intervention | Participants (Count of Participants) |
|---|
| Immediate Treatment Group | 7 |
| Delayed Treatment Group | 5 |
Time to Confirmed Expanded Disability Status Scale (EDSS) Progression Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With Confirmed EDSS Progression at Selected Points in Time
"EDSS progression was defined as an increase in the expanded disability status scale (EDSS) of 1.0 point compared to the lowest EDSS score obtained during the screening or baseline visit, if this score was <= 5.5. A confirmed EDSS progression status was defined as an EDSS progression observed at two consecutive scheduled visits at least 140 days apart from each other. The EDSS scale is a method of quantifying disability in multiple sclerosis in eight functional systems and values vary between 0=normal neurological examination and 10=death due to MS measured in half-points on a scale." (NCT00185211)
Timeframe: up to 60 months after start of treatment
| Intervention | percentage of particip. with EDSS progr. (Number) |
|---|
| Kaplan-Meier estimate at year 2 | Kaplan-Meier estimate at year 3 | Kaplan-Meier estimate at year 5 |
|---|
| Initial IFNB-1b (Interferon Beta-1b) | 12.8 | 16.8 | 24.9 |
,| Initial Placebo | 19.9 | 25.3 | 28.9 |
Time to Clinically Definite Multiple Sclerosis (CDMS) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS at Selected Points in Time
"CDMS could be reached due to a qualifying relapse or sustained progression of 1.5 points on the expanded disability status scale (EDSS) as compared to the lowest EDSS obtained during screening or Day 1. The validity of CDMS diagnoses was confirmed by a central committee. The EDSS scale quantifies disability in MS in 8 functional systems, values vary between 0=normal neurological examination and 10=death due to MS measured in half-points on an ordinal scale. Time to CDMS = date of CDMS - date of Day 1 + 1 or time to CDMS = date of last clinical visit - date of Day 1 + 1 (right-censored)" (NCT00185211)
Timeframe: up to 60 months after start of treatment
| Intervention | cum. percentage of particip. with CDMS (Number) |
|---|
| Kaplan-Meier estimate at year 2 | Kaplan-Meier estimate at year 3 | Kaplan-Meier estimate at year 5 |
|---|
| Initial IFNB-1b (Interferon Beta-1b) | 26.9 | 36.7 | 46.2 |
,| Initial Placebo | 45.0 | 51.2 | 57.3 |
Relapse-based Efficacy Domain: Time to Multiple Sclerosis (MS) According to McDonald Criteria
MS according to the criteria by McDonald was reached if, in addition to the single clinical demyelinating event, both dissemination in space and dissemination in time were established by MRI-criteria or a new relapse. Time to McDonald MS is the difference of date of McDonald MS to the date of Day 1 + 1. For subjects without McDonald MS, time to McDonald MS is the difference from the maximum (date of last magnetic resonance imaging scan, date of last clinical visit) to the date of Day 1 + 1 (right-censored observation). (NCT00185211)
Timeframe: up to 60 months after start of treatment
| Intervention | months (Median) |
|---|
| Initial IFNB-1b (Interferon Beta-1b) | 9.4 |
| Initial Placebo | 6 |
Relapse-based Efficacy Domain: Hazard Ratio for Recurrent Relapses
A relapse was defined as the appearance of a new neurological abnormality or the reappearance of a neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The time to the onset of recurrent relapses was determined for each subject according to the counting process representation for recurrent events. Time to a relapse was right-censored if a relapse-risk period ended without relapse. Based on the Andersen-Gill model the hazard ratio for recurrent relapses was estimated. Annualized relapse rates are provided as another outcome measure. (NCT00185211)
Timeframe: up to 60 months after start of treatment
| Intervention | Ratio (Number) |
|---|
| All Subjects | 0.797 |
Relapse-based Efficacy Domain (Supportive): Annualized Relapse Rate
The annualized relapse rate is defined as total number of relapses up to month 60 divided by the total observation time (last clinical visit minus first day of study treatment administration plus 1 of all participants) in years. (NCT00185211)
Timeframe: up to 60 months after start of treatment
| Intervention | number of relapses per patient and year (Mean) |
|---|
| Initial IFNB-1b (Interferon Beta-1b) | 0.2139 |
| Initial Placebo | 0.2695 |
MRI-based Efficacy Domain: Percentage Change of Brain Volume From Screening MRI to Month 60
Two-timepoint percentage brain volume change was estimated with Structural Image Evaluation, using Normalisation, of Atrophy (SIENA) software. The measurements describe the percentage change from screening in brain volume at month 60. (NCT00185211)
Timeframe: 60 months after start of treatment
| Intervention | Percentage of brain volume (Median) |
|---|
| Initial IFNB-1b (Interferon Beta-1b) | -2.281 |
| Initial Placebo | -1.771 |
MRI-based Efficacy Domain: Absolute Change of Volume of Black Holes From Screening MRI to Month 60
Absolute change of volume of black holes from screening MRI to month 60 was calculated as volume of black holes at month 60 minus volume of black holes at screening. (NCT00185211)
Timeframe: 60 months after start of treatment
| Intervention | cubic millimeter (Median) |
|---|
| Initial IFNB-1b (Interferon Beta-1b) | 0 |
| Initial Placebo | 0 |
Disability-based Efficacy Domain: Multiple Sclerosis Functional Composite (MSFC) at Month 60
"The MSFC score consists of three sub-tests (Timed-25-Foot-Walk, 9-Hole-Peg-Test, 3 Paced Auditory Serial Addition Test [PASAT]). Standardized results (Z-scores) of the sub-tests and the overall MSFC Z-score as an average of the three Z-scores were derived using baseline data pooled over both treatment arms as reference population. Higher Z-scores reflect a better neurological status." (NCT00185211)
Timeframe: 60 months after start of treatment
| Intervention | Z-scores (Median) |
|---|
| Initial IFNB-1b (Interferon Beta-1b) | 0.226 |
| Initial Placebo | 0.225 |
MRI-based Efficacy Domain: Absolute Change of T2 Lesion Volume From Screening MRI to Month 60
Absolute change of T2 lesion volume from screening MRI to month 60 was calculated as T2 lesion volume at month 60 minus T2 lesion volume at screening. (NCT00185211)
Timeframe: 60 months after start of treatment
| Intervention | cubic millimeter (Median) |
|---|
| Initial IFNB-1b (Interferon Beta-1b) | -123.0 |
| Initial Placebo | -194.5 |
MRI (Magnet-Resonance Imaging)-Based Efficacy Domain: Cumulative Number of Newly Active Lesions at Month 60
Newly active lesions are defined as displaying either new Gadolinium (Gd)-enhancement on T1-weighted scans or non-enhancement on T1-weighted scan but new on T2-weighted scan. The numbers of newly active lesions on yearly MRI scans were summed up to the cumulative number. (NCT00185211)
Timeframe: up to 60 months after start of treatment
| Intervention | cumulative number of lesions (Median) |
|---|
| Initial IFNB-1b (Interferon Beta-1b) | 4 |
| Initial Placebo | 7 |
Functional Assessment of Multiple Sclerosis (FAMS) Trial Outcome Index (TOI) at Month 60
As an index of health related quality of life in people diagnosed with MS, the FAMS Trial Outcome Index covers overall physical health (sum of sub-scale scores Mobility, Symptoms, Thinking/Fatigue, Additional Concerns) with a score range from 0 to 148. A higher score reflects a higher overall physical health as reported by patients. (NCT00185211)
Timeframe: 60 months after start of treatment
| Intervention | units on a scale (Median) |
|---|
| Initial IFNB-1b (Interferon Beta-1b) | 125 |
| Initial Placebo | 125 |
Chest Cavity Size
(NCT00201123)
Timeframe: 16 Weeks
| Intervention | millimeters (Mean) |
|---|
| Baseline | 16 Weeks |
|---|
| Aerosol Interferon Gamma for TB | 39 | 29 |
,| DOTS Control Group | 34 | 20 |
,| Subcutaneous Interferon Gamma for TB | 34 | 18 |
Sputum Conversion
(NCT00201123)
Timeframe: Measured at 16 Weeks
| Intervention | percentage of participants (Number) |
|---|
| DOTS Control Group | 36 |
| Aerosol Interferon Gamma for TB | 60 |
| Subcutaneous Interferon Gamma for TB | 36 |
Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels
(NCT00201123)
Timeframe: 16 Weeks
| Intervention | cells/mL (Median) |
|---|
| Lymphocytes Week 0 | Lymphocytes Week 16 | Machrophages Week 0 | Machrophages Week 16 | Neutrophils Week 0 | Neutrophils Week 16 |
|---|
| DOTS | 4 | 15 | 60 | 64 | 28 | 11 |
,| Nebulized rlFN-y | 5 | 15 | 60 | 63 | 24 | 4 |
,| Subcutaneous rlFN-y | 6 | 22 | 62 | 66 | 30 | 2 |
Participants Achieving SVR Categorized by Time of Response
rapid virologic response assessed at 4 weeks, early virologic response assessed at 8-12 weeks, late virologic response assessed at 16-24 weeks (NCT00211692)
Timeframe: 24 weeks after end of treatment
| Intervention | participants (Number) |
|---|
| rapid virologic response (n=20) | early virologic response (n=13) | late virologic response (n=9) |
|---|
| Overall | 15 | 4 | 2 |
The Primary Endpoint Would be the Number Who Achieve a Sustained Virologic Response.
Overall sustained virologic response for entire cohort and individual sustained virologic response for different arms of study (NCT00211692)
Timeframe: 24 weeks after the end of treatment
| Intervention | participants (Number) |
|---|
| A (52 Weeks Treatment) | 11 |
| B (Duration Based on Viral Response) | 10 |
Overall Number of Serious Adverse Events
(NCT00211692)
Timeframe: through end of study up to 72 weeks
| Intervention | participants (Number) |
|---|
| Overall | 2 |
Number of Participants Discontinuing Early From Study Treatment
(NCT00211692)
Timeframe: through end of study up to 72 weeks
| Intervention | participants (Number) |
|---|
| Overall | 26 |
Change in MRI Composite Score
MRI composite score (Z4 score) - the unweighted sum of the individual Z scores for enhanced tissue volume, T2 lesion burden, equivalence of the T1 hypointense lesion burden, normalized CSF (an inverse measure of atrophy with the appropriate sign so that all scores are directionally compatible - larger is worse) MRI enhancement status at baseline (0, 1-4, and 5 or more enhancing lesions) (NCT00211887)
Timeframe: Baseline to month 36
| Intervention | z score (Mean) |
|---|
| IFN + GA | -0.02 |
| IFB-1a | 0.05 |
| Glatiramer | 0.10 |
ARR - PDEs
Annualized relapse rate of protocol-defined exacerbations Protocol defined relapse - an relapse seen within 7 days of onset, verified by the treating physician and independently observed as a change in EDSS by the examining physician. This relapse is defined as: the appearance of a new symptom or worsening of an old symptom, attributable to MS; accompanied by a change in the neurologic examination (defined as a 0.5 or greater increase in the EDSS over the last scheduled or unscheduled visit or a 2 point change in one functional system or a 1 point change in two functional systems, except bladder and cognitive changes); lasting at least 24 hours in the absence of fever; and preceded by stability or improvement for at least 30 days. (NCT00211887)
Timeframe: Baseline to Month 36
| Intervention | relapses per year (Number) |
|---|
| IFN + GA | 0.12 |
| IFB-1a | 0.16 |
| Glatiramer | 0.11 |
Change in the Multiple Sclerosis Functional Composite
"positive indicates improvement~The Multiple Sclerosis Functional Composite (MSFC) is a scale measuring pyramidal functions, sensory functions, cerebellar functions, bowel & bladder functions,brain stem functions, mental functions, and visual functions from 0 to 6.~0= normal 6= severe loss" (NCT00211887)
Timeframe: Baseline to month 36
| Intervention | units on a scale (Median) |
|---|
| IFN + GA | 0.1 |
| IFB-1a | 0.1 |
| Glatiramer | 0.2 |
Confirmed Progression on the Expanded Disability Status Scale
"% with EDSS progression~Confirmed progression in a participant was defined as a 1.0 increase in the EDSS from baseline, when baseline <=5.0; or an increase of 0.5 from baseline, when baseline >=5.5, sustained for 6 months (2 successive quarterly visits), as assessed by the blinded EDSS examiner and confirmed centrally." (NCT00211887)
Timeframe: Baseline to Month 36
| Intervention | percentage of participants (Number) |
|---|
| IFN + GA | 23.9 |
| IFB-1a | 21.6 |
| Glatiramer | 24.8 |
Safety and Tolerability as Defined by the Number of Subjects With Flu-like Syndrome, Fever, Myalgia, Injection Site Reactions, Injection Site Reactions Pain, Asthenia, Headache, Liver Function Abnormalities, and Bone Marrow Function Abnormalities
Outcome measures are given as the number of patients with common toxicity by the Common Toxicity Criteria (CTC). Toxicity grading is: Grade 1: no study drug action recommended, Grade 2: Dose reduction or interruption of study treatment should be considered (grade 2 Lymphocyte toxicity required no study drug action), Grade 3: Dose reduction or interruption should be considered; interruption is recommended, and Grade 4: Interruption of study drug is recommended (Grade 4 laboratory toxicity was reported as a serious adverse event). Liver and bone marrow abnormalities are measured by lab tests. (NCT00235989)
Timeframe: At End of Study Visit (week 234)
| Intervention | participants (Number) |
|---|
| Incidence of flu-like syndrome | Incidence of fever | Incidence of myalgia | Incidence of injection site reactions | Incidence of injection site reactions pain | Incidence of asthenia | Incidence of headache | Incidence of grade 1 toxicity (ALAT) | Incidence of grade 2 toxicity (ALAT) | Incidence of grade 3 toxicity (ALAT) | Incidence of grade 4 toxicity (ALAT) | Incidence of grade 1 toxicity (ASAT) | Incidence of grade 2 toxicity (ASAT) | Incidence of grade 3 toxicity (ASAT) | Incidence of grade 4 toxicity (ASAT) | Incidence of grade 1 toxicity (Bilirubin total) | Incidence of grade 2 toxicity (Bilirubin total) | Incidence of grade 3 toxicity (Bilirubin total) | Incidence of grade 4 toxicity (Bilirubin total) | Incidence of grade 1 toxicity (Leukocytes) | Incidence of grade 2 toxicity (Leukocytes) | Incidence of grade 3 toxicity (Leukocytes) | Incidence of grade 4 toxicity (Leukocytes) | Incidence of grade 1 toxicity (Lymphocytes) | Incidence of grade 2 toxicity (Lymphocytes) | Incidence of grade 3 toxicity (Lymphocytes) | Incidence of grade 4 toxicity (Lymphocytes) | Incidence of grade 1 toxicity (Platelets) | Incidence of grade 2 toxicity (Platelets) | Incidence of grade 3 toxicity (Platelets) | Incidence of grade 4 toxicity (Platelets) | Incidence of grade 1 toxicity (Hemoglobin) | Incidence of grade 2 toxicity (Hemoglobin) | Incidence of grade 3 toxicity (Hemoglobin) | Incidence of grade 4 toxicity (Hemoglobin) |
|---|
| ET: IFNB-1b 250 mcg => 250 mcg | 1 | 1 | 0 | 2 | 0 | 4 | 2 | 4 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 10 | 0 | 0 | 0 | 3 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| ET: IFNB-1b 250 mcg => 500 mcg | 7 | 0 | 0 | 3 | 0 | 3 | 3 | 9 | 0 | 0 | 0 | 7 | 0 | 0 | 0 | 14 | 0 | 0 | 0 | 6 | 2 | 0 | 0 | 5 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
,| ET: IFNB-1b 500 mcg => 250 mcg | 1 | 0 | 0 | 3 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| ET: IFNB-1b 500 mcg => 500 mcg | 4 | 1 | 1 | 4 | 1 | 2 | 2 | 8 | 0 | 0 | 0 | 8 | 0 | 0 | 0 | 10 | 1 | 0 | 0 | 4 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
Frequency (Number of Patients Per Group Defined by Cut Off Values and Per Treatment Arm) of Neutralizing Antibody (NAb) Titer to IFNB-1b
Serum samples for analysis of NAbs to interferon (IFN) beta-1b were collected in Study 307000A. In the extension study, NAbs were also monitored for information on persistence or resolution. Serum samples of about 6 mL for NAbs were drawn at Weeks 10, 24, 52, 78, 104 130, 156, 182, 208, 234, 260, 286 or the EOS visit. (NU/ml=neutralizing units/ml). (NCT00235989)
Timeframe: At End of Study Visit (week 234)
| Intervention | participants (Number) |
|---|
| NAbs titer, cut-off value 20 NU/ml (minimum) | NAbs titer, cut-off value 100 NU/ml (minimum) | NAbs titer, cut-off value 400 NU/ml (minimum) |
|---|
| ET: IFNB-1b 250 mcg => 250 mcg | 2 | 1 | 1 |
,| ET: IFNB-1b 250 mcg => 500 mcg | 3 | 2 | 1 |
,| ET: IFNB-1b 500 mcg => 250 mcg | 0 | 0 | 0 |
,| ET: IFNB-1b 500 mcg => 500 mcg | 5 | 2 | 1 |
Gadolinium-enhancing (Gd+)Lesion Number Change.
Before treatment is the number of lesions per image from months -3, -2, -1, and 0. During treatment is the number of lesions from months 1,2, and 3. The mean number of Gd+ lesions during each treatment period was calculated for each patient as the total number of Gd+ lesions observed across all images divided by the number of images. Hence, the mean number of Gd+ lesions per patient represents the number of lesions per MRI. (NCT00246324)
Timeframe: 8 months
| Intervention | Gd+ lesions (Median) |
|---|
| Inteferon, Then Interferon With Doxycycline | 4.0 |
Number of Patients in Whom Tumor Was Resectable
Tumor response is measured in terms of resectability, as measured by CT scan at 2 weeks after completion of each course. A CT scan of the chest abdomen and pelvis will be performed in order to evaluate for the presence of metastatic disease. If no metastatic disease, emphasis will be paid to the local tumor. Evaluation of the growth/regression of the tumor will be made as it relates to resectability. If potential for resection then surgery will be recommended. This protocol will be followed after each cycle. (NCT00262951)
Timeframe: Up to 5 Years or Until Disease Progression
| Intervention | Participants (Number) |
|---|
| Pancreatic Adenocarcinoma Patients | 7 |
Overall Survival
In all patients, measured from the date of the patient's registration in this study, until the date of the patient's death or date last known alive (if observation was censored). (NCT00262951)
Timeframe: Up to 5 Years or Date of Death, Whichever Occurred First
| Intervention | Months (Median) |
|---|
| Pancreatic Adenocarcinoma Patients | 11.5 |
Sustained Virologic Response, Defined as a Plasma HCV-RNA (Hepatitis C Ribonucleic Acid) Level Below the LLQ (Lower Level of Quantitation) at 24 Weeks Post-treatment.
LLQ = 30 IU/mL by reverse transcription polymerase chain reaction (RT-PCR) (Taqman Roche) (NCT00265395)
Timeframe: 48 or 72 weeks of treatment plus 24 weeks of follow-up.
| Intervention | Participants (Number) |
|---|
| Standard Therapy (48-week Treatment) | 37 |
| Extended Therapy (72-week Treatment) | 35 |
Percentage of Participants With Best Cytogenetic Response (Second-line Treatment)
"Bone marrow aspirate was performed to evaluate cytogenetic results (percentage of Ph chromosome (Ph+) containing metaphases) and the amount of blasts and promyelocytes in bone marrow to establish cytogenetic response.~Major Cytogenetic Response= Complete Response or Partial Response. Complete Cytogenetic Response= 0 % of Ph+ metaphases (out of 20 metaphases). Partial Cytogenetic Response= > 0 and ≤ 35 % Ph+ metaphases (out of 20 metaphases). The percentage of participants with cytogenetic response in each category was calculated." (NCT00333840)
Timeframe: 144 months
| Intervention | Percentage of participants (Number) |
|---|
| Major Cytogenic Response | Complete Cytogenic Response | Partial Cytogenic Response |
|---|
| IFN-a + Ara-C to Imatinib | 86.0 | 81.0 | 5.0 |
,| Imatinib to IFN-a + Ara-C | 14.3 | 7.1 | 7.1 |
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
Overall survival was defined as the time between date of randomization and death due to any cause. The time was censored at last examination date for patients who were still being treated and at date of last contact for patients who discontinued treatment. Kaplan-Meier estimates of the percentage of participants at each time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment. (NCT00333840)
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
| Intervention | Percentage of participants (Number) |
|---|
| 12 months (n = 553, 553) | 24 months (n = 542, 512) | 36 months (n = 518, 471) | 48 months (n = 492, 441) | 60 months (n = 475, 411) | 72 months (n = 461, 388) | 84 months (n = 446, 373) | 96 months (n = 430, 358) | 108 months (n = 391, 315) | 120 months (n = 368, 299) | 132 months (n = 356, 288) | 144 months (n = 250, 199) |
|---|
| IFN-a + Ara-C | 97.7 | 93.6 | 89.8 | 87.7 | 85.4 | 83.8 | 83.1 | 81.4 | 79.9 | 78.8 | 77.7 | 75.4 |
,| Imatinib (STI571) | 98.9 | 96.0 | 92.4 | 90.4 | 89.4 | 88.2 | 86.6 | 85.4 | 84.3 | 83.3 | 82.8 | 81.3 |
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
Time to progression to AP/BC is defined as the time between randomization and either of the following events on treatment: death (due to CML when reported as primary reason for discontinuation of treatment) or progression to Accelerated Phase or Blast Crisis and is censored at last examination date for patients without event. No data after discontinuation of study treatment was included. The Kaplan Meier estimates of the percentage of participants with survival without progression to AP/BC at the given time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment. (NCT00333840)
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
| Intervention | Percentage of participants (Number) |
|---|
| 12 months (n = 553, 553) | 24 months (n = 513, 388) | 36 months (n = 461, 337) | 48 months (n = 431, 311) | 60 months (n = 409, 289 ) | 72 months (n = 384, 265) | 84 months (n = 358, 236) | 96 months (n = 338, 220) | 108 months (n = 305, 189) | 120 months (n = 272, 175) | 132 months (n = 259, 165) | 144 months (n = 145, 94) |
|---|
| IFN-a + Ara-C | 92.9 | 90.0 | 87.9 | 84.7 | 83.5 | 83.1 | 82.4 | 82.4 | 82.4 | 82.4 | 82.4 | 82.4 |
,| Imatinib (STI571) | 98.5 | 95.7 | 94.0 | 93.1 | 92.7 | 92.7 | 92.7 | 92.4 | 92.1 | 92.1 | 92.1 | 92.1 |
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
"Event-free survival is defined as the time between randomization and the earliest of any of the following events on treatment:~progression to Accelerated Phase (AP) or Blast Crisis (BC)~loss of Complete Hematological Response (CHR)~loss of Major Cytogenetic Response (MCyR) confirmed~loss of Major Cytogenetic Response (MCyR) unconfirmed~increase in white blood cell count (WBC) if approved by the Study Management Committee (SMC)~death (due to any cause when reported as primary reason for discontinuation of treatment).~Kaplan Meier estimates of the percentage of participants with Event Free Survival at the given time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment." (NCT00333840)
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
| Intervention | Percentage of participants (Number) |
|---|
| 12 months (n = 553, 553) | 24 months (n = 505, 332) | 36 months (n = 448, 263) | 48 months (n = 415, 241) | 60 months (n = 395, 223) | 72 months (n = 376, 207) | 84 months (n = 352, 181) | 96 months (n = 334, 166) | 108 months (n = 301, 141) | 120 months (n = 269, 130) | 132 months (n = 257, 124) | 144 months (n = 143, 76) |
|---|
| IFN-a + Ara-C | 79.4 | 70.0 | 67.0 | 63.7 | 61.9 | 60.1 | 59.0 | 58.3 | 56.6 | 56.6 | 56.6 | 51.8 |
,| Imatinib (STI571) | 96.6 | 89.6 | 85.3 | 83.9 | 83.2 | 83.0 | 82.0 | 81.0 | 79.9 | 79.6 | 79.6 | 79.6 |
Number of Participants With Serious Adverse Events as a Measure of Safety (Second-line Treatment)
A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant (NCT00333840)
Timeframe: 144 months
| Intervention | Participants (Number) |
|---|
| Imatinib to IFN-a + Ara-C | 2 |
| IFN-a + Ara-C to Imatinib | 160 |
Percentage of Participants With Best Cytogenetic Response (First-line Treatment)
"Bone marrow aspirate was performed to evaluate cytogenetic results (percentage of Philadelphia chromosome positive (Ph+) metaphases) and amount of blasts and promyelocytes in bone marrow to establish cytogenetic response.~Major Cytogenetic Response= Complete Response or Partial Response. Complete Cytogenetic Response= 0 % of Ph+ metaphases (out of 20 metaphases). Partial Cytogenetic Response= > 0 and ≤ 35 % of Ph+ metaphases (out of 20 metaphases). The percentage of participants with cytogenetic response in each category was calculated." (NCT00333840)
Timeframe: 144 months
| Intervention | Percentage of participants (Number) |
|---|
| Major Cytogenic Response | Complete Cytogenic Response | Partial Cytogenic Response |
|---|
| IFN-a + Ara-C | 23.3 | 11.6 | 11.8 |
,| Imatinib (STI571) | 89.0 | 82.8 | 6.1 |
Number of Participants With Serious Adverse Events as a Measure of Safety (First-line Treatment)
A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant (NCT00333840)
Timeframe: 144 months
| Intervention | Participants (Number) |
|---|
| Imatinib (STI571) | 226 |
| IFN-a + Ara-C | 163 |
Percentage of Participants With Major Molecular Response (Second-line Treatment)
Major Molecular Response was determined using a quantitative polymerase chain reaction (PCR) laboratory test and was defined as BCR-ABL protein transcripts of ≤ 0.1% according to the international scale. (NCT00333840)
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
| Intervention | Percentage of participants (Number) |
|---|
| 12 months (n = 86) | 24 months (n = 62) | 36 months (n = 130) | 48 months (n = 216) | 60 months (n = 174) | 72 months (n = 146) | 84 months (n = 139) | 96 months (n = 138) | 108 months (n = 120) | 120 months (n = 84) | 132 months (n = 31) | 144 months |
|---|
| IFN-a + Ara-C to Imatinib | 51.2 | 69.4 | 78.5 | 81.9 | 86.2 | 91.1 | 86.3 | 87.0 | 90.0 | 85.7 | 90.3 | NA |
Percentage of Participants With Major Molecular Response (First-line Treatment)
Major Molecular Response was determined using a quantitative polymerase chain reaction (PCR) laboratory test and was defined as BCR-ABL protein transcripts of ≤ 0.1% according to the international scale. (NCT00333840)
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
| Intervention | Percentage of participants (Number) |
|---|
| 12 months (n= 305, 83) | 24 months (n= 102, 12) | 36 months (n= 68, 7) | 48 months (n= 305, 12) | 60 months (n= 316, 10) | 72 months (n= 292, 9) | 84 months (n= 247, 8) | 96 months (n= 228, 4) | 108 months (n= 233, 0) | 120 months (n= 204, 0) | 132 months (n= 168, 0) | 144 months (n= 1, 0) |
|---|
| IFN-a + Ara-C | 9.6 | 25.0 | 28.6 | 58.3 | 100.0 | 88.9 | 87.5 | 100.0 | NA | NA | NA | NA |
,| Imatinib (STI571) | 50.2 | 69.6 | 76.5 | 77.0 | 88.0 | 88.0 | 91.9 | 92.5 | 93.6 | 93.1 | 92.3 | 100.0 |
Percentage of Participants With Event Free Survival Events (All Randomized Participants)
"Event-free survival is defined as the time between randomization and the earliest of any of the following events on treatment:~progression to Accelerated Phase (AP) or Blast Crisis (BC)~loss of Complete Hematological Response (CHR)~loss of Major Cytogenic Response (MCyR) confirmed~loss of Major Cytogenic Response (MCyR) unconfirmed~increase in white blood cell count (WBC) if approved by the Study Management Committee (SMC)~death (due to any cause when reported as primary reason for discontinuation of treatment).~The percentage of participants with Event Free Survival events in each category was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment." (NCT00333840)
Timeframe: 144 months
| Intervention | Percentage of participants (Number) |
|---|
| Participants with events | Progression to AP or BC | Loss of CHR | Loss of MCyR (confirmed) | Loss of MCyR (unconfirmed) | Increase of WBC | Death |
|---|
| IFN-a + Ara-C | 32.2 | 12.8 | 7.6 | 5.4 | 1.1 | 3.4 | 1.8 |
,| Imatinib (STI571) | 17.9 | 6.9 | 2.7 | 4.2 | 0.9 | 0.2 | 3.1 |
Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00336479)
Timeframe: 12 weeks after the completion of study drug dosing (up to Week 60)
| Intervention | percentage of participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 36.0 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | 58.2 |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | 53.2 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | 35.3 |
Number of Subjects With Viral Relapse
Viral relapse was defined as having detectable HCV RNA during antiviral follow-up. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00336479)
Timeframe: After last dose of study drug up to antiviral follow-up (up to Week 72)
| Intervention | participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 8 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | 3 |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | 1 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | 3 |
Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir
Only subjects who received telaprevir were to be analyzed for this outcome. Maximum, minimum and average plasma concentrations observed during assessment period were reported. (NCT00336479)
Timeframe: Day 1, 4, 8, 15, 22, 29, 43, 57, 71, 85
| Intervention | nanogram per milliliter (ng/mL) (Mean) |
|---|
| Cmax | Cmin | Cavg |
|---|
| Telaprevir | 3032.48 | 2235.51 | 2738.46 |
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
"AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Study drug includes all investigational agents (including placebo, if applicable) administered during the course of the study." (NCT00336479)
Timeframe: Baseline up to Week 48
| Intervention | participants (Number) |
|---|
| AEs | SAEs |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 75 | 4 |
,| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | 79 | 10 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | 17 | 3 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | 79 | 5 |
Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00336479)
Timeframe: 24 weeks after the completion of study drug dosing (up to Week 72)
| Intervention | percentage of participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 41.3 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | 67.1 |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | 60.8 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | 35.3 |
Percentage of Participants Free of 3-month and 6-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Extension Phase of the Study
The EDSS is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, other functions). An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the EDSS score based on the following criteria: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. Percent of patients free of disability progression was calculated using the Kaplan-Meier method. (NCT00340834)
Timeframe: Baseline to end of study (up to approximately 4.5 years)
| Intervention | Percentage of participants (Number) |
|---|
| Free of 3-month progression | Free of 6-month progression |
|---|
| Fingolimod 0.5 mg | 71.28 | 79.76 |
,| Fingolimod 1.25 mg | 67.01 | 79.54 |
,| Interferon β-1a µg/Fingolimod 1.25 or 0.5 mg | 73.40 | 81.61 |
Number of New or Newly Enlarged T2 Lesions in Comparison With Baseline in the Core Phase of the Study
The number of new or newly enlarged T2 lesions in comparison to baseline was assessed with T2-weighted magnetic resonance image (MRI) scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2-weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis. (NCT00340834)
Timeframe: Baseline to Month 12
| Intervention | T2 lesions (Mean) |
|---|
| Fingolimod 1.25 mg | 1.6 |
| Fingolimod 0.5 mg | 1.6 |
| Interferon β-1a µg/Fingolimod 1.25 or 0.5 mg | 2.6 |
Estimated Annualized Aggregate Relapse Rate (ARR) in the Core Phase of the Study
The ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was calculated using negative binomial regression adjusted by treatment, country, number of relapses in the previous 2 years, and the baseline Expanded Disability Status Scale score. (NCT00340834)
Timeframe: Baseline to Month 12
| Intervention | Estimate relapses per year (Number) |
|---|
| Fingolimod 1.25 mg | 0.203 |
| Fingolimod 0.5 mg | 0.161 |
| Interferon β-1a µg/Fingolimod 1.25 or 0.5 mg | 0.331 |
Number of New or Newly Enlarged T2 Lesions in the Extension Phase of the Study
The number of new or newly enlarged T2 lesions in comparison to baseline was assessed with T2-weighted magnetic resonance image (MRI) scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2-weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis. (NCT00340834)
Timeframe: Month 12 to end of study (up to approximately 3.5 years)
| Intervention | T2 lesions (Mean) |
|---|
| Month 12 to Month 24 | Month 24 to Month 36, n=255, 289, 258 | Month 36 to Month 48, n=36, 34, 35 | Last MRI scan to end of study, n=275, 309, 290 |
|---|
| Fingolimod 0.5 mg | 0.87 | 1.04 | 0.59 | 0.86 |
,| Fingolimod 1.25 mg | 1.08 | 1.40 | 0.97 | 1.75 |
,| Interferon β-1a µg/Fingolimod 1.25 or 0.5 mg | 0.97 | 0.72 | 0.49 | 1.03 |
Percentage of Participants Free of 3-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Core Phase of the Study
The EDSS is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, other functions). An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the EDSS score based on the following criteria: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. Percent of patients free of disability progression was calculated using the Kaplan-Meier method. (NCT00340834)
Timeframe: Baseline to Month 12
| Intervention | Percentage of participants (Number) |
|---|
| Fingolimod 1.25 mg | 93.3 |
| Fingolimod 0.5 mg | 94.1 |
| Interferon β-1a µg/Fingolimod 1.25 or 0.5 mg | 92.1 |
Estimated Annualized Aggregate Relapse Rate (ARR) in the Core and Extension Phases of the Study
The ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was calculated using negative binomial regression adjusted by treatment, country, number of relapses in the previous 2 years, and the baseline Expanded Disability Status Scale score. (NCT00340834)
Timeframe: Month 0 to end of study (up to approximately 4.5 years)
| Intervention | Estimated relapses per year (Number) |
|---|
| Month 12 to Month 24, n=330, 356, 341 | Month 24 to Month 36, n=287, 321, 293 | Month 36 to Month 48, n=267, 303, 271 | Month 48 to end of study, n=36, 38, 29 | Month 0 to end of study, n=420, 429, 431 |
|---|
| Fingolimod 0.5 mg | 0.182 | 0.110 | NA | NA | 0.166 |
,| Fingolimod 1.25 mg | 0.156 | 0.116 | NA | NA | 0.192 |
,| Interferon β-1a µg/Fingolimod 1.25 or 0.5 mg | 0.266 | 0.121 | NA | NA | 0.271 |
Disease-free Survival
Median number of days to progression of disease in participants who stopped all treatment as directed by the protocol. (NCT00363649)
Timeframe: Up to 8 years
| Intervention | days (Median) |
|---|
| Arm A | 82 |
| Arm B | 98 |
Early Discontinuation
Number of participants unable to complete protocol-specified treatment due to toxicity. (NCT00363649)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Arm A | 10 |
| Arm B | 0 |
Progression-free Survival
Number of patients alive and without disease progression or relapse (NCT00363649)
Timeframe: 1 year after treatment has been stopped
| Intervention | Participants (Count of Participants) |
|---|
| Arm A | 2 |
| Arm B | 0 |
Time to Complete Molecular Remission
Number of months from randomization to molecular remission as defined by polymerase chain reaction negativity. (NCT00363649)
Timeframe: Up to 27 months
| Intervention | months (Median) |
|---|
| Arm A | 10 |
| Arm B | 16.3 |
Complete Remission Rate
Percentage of patients who achieved molecular remission as defined by polymerase chain reaction negativity. (NCT00363649)
Timeframe: Up to 18 months
| Intervention | percentage of participants (Number) |
|---|
| Arm A | 61.1 |
| Arm B | 62.5 |
Number of Participants Testing Positive for Neutralising Antibody (NAb)
Participants who were NAb+ at 48 weeks (or at the last available NAb assessment up to Week 48). The NAb+ value was defined as NAb ≥ 20 NU/ml. (NCT00367484)
Timeframe: 48 Weeks
| Intervention | NAb+ participants (Number) |
|---|
| Rebif® (Clone 484-39) | 73 |
Expanded Disability Status Scale (EDSS)
The EDSS is a scale based on the standardized neurological examination which comprised of optic, brain stem/cranial nerves, pyramidal, cerebellar, sensory, vegetative, and cerebral functions, as well as walking ability. The EDSS scores range from 0.0 (normal) to 10.0 (dead). A score of 2 to 3 indicates minimal to moderate disability. (NCT00370071)
Timeframe: Pre-treatment on Day 1, Week 24
| Intervention | Scores on a scale (Mean) |
|---|
| Pre-treatment | Week 24 |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | 2.06 | 1.81 |
Assessment of Relapses: Relapse Severity
A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature >37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment. A major relapse was defined based on changes on EDSS with the following additional criteria to be met: objective neurological impairment, correlating with the subject's reported symptoms, defined as either increase in at least one of the functional systems of the EDSS score or increase of the total EDSS score. Relapses which did not meet the criteria of major relapses were considered as non-major. (NCT00370071)
Timeframe: Baseline up to Week 24
| Intervention | relapses (Number) |
|---|
| Major | Non-major |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | 1 | 12 |
Assessment of Relapses: Number of Relapses
"A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature >37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment. In the categories listed below, N signifies the number of subjects evaluable for the timepoints, and same subjects were counted more than once under each category." (NCT00370071)
Timeframe: 3 and 6 months
| Intervention | relapses (Number) |
|---|
| 3 months (N=6) | 6 months (N=6) |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | 6 | 7 |
Percentage of Subjects Without EDSS Progression
The EDSS is a scale based on the standardized neurological examination which comprised of optic, brain stem/cranial nerves, pyramidal, cerebellar, sensory, vegetative, and cerebral functions, as well as walking ability.The EDSS scores range from 0.0 (normal) to 10.0 (dead). A score of 2 to 3 indicates minimal to moderate disability. An EDSS progression was defined as increase in EDSS greater than or equal to (>=) 1.0 points (in the treatment period as compared to baseline). (NCT00370071)
Timeframe: Baseline up to Week 24
| Intervention | percentage of subjects (Number) |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | 87.2 |
Difference Between the Number of New or Enlarging T2 Lesions Per 3 Months During the 6-month Treatment Period and the Number of New or Enlarging T2 Lesions During 3-month Pre-treatment
This secondary endpoint (component of the primary endpoint) was calculated by subtracting the number of new or enlarging T2 lesions during the 3-month pre-treatment period from the cumulative number of new or enlarging T2 lesions during the 6-month treatment period divided by 2 (number of new T2 lesions per three months) based on non-enhancing lesions on T1 weighted scans (NCT00370071)
Timeframe: after 6 months of treatment as compared to the 3-month pre-treatment
| Intervention | lesions (Median) |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | 0 |
Volume of Gadolinium-enhancing Lesions at Baseline, Weeks 12 and 24
"In the categories listed below, N signifies the number of subjects evaluable for the timepoints." (NCT00370071)
Timeframe: Baseline, Weeks 12 and 24
| Intervention | cubic millimeter (mm^3) (Mean) |
|---|
| Baseline (N=39) | Week 12 (N=38) | Week 24 (N=37) |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | 585 | 93 | 648 |
Difference Between the Number of New Gadolinium (Gd)-Enhancing Lesions Per 3 Months During the 6-month Treatment Period and the Number of New Gd-enhancing Lesions During 3-month Pre-treatment
This secondary endpoint (component of the primary endpoint) was calculated by subtracting the number of new Gd-enhancing lesions during the 3-month pre-treatment period from the cumulative number of new Gd-enhancing lesions during the 6-month treatment period divided by 2 (number of new Gd-enhancing lesions per three months) (NCT00370071)
Timeframe: after 6 months of treatment as compared to 3-month pre-treatment
| Intervention | lesions (Median) |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | -0.5 |
Assessment of Relapses: Relapse Rate
A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature more than (>) 37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment. The relapse rate was calculated on an annualized basis. Annualized relapse rate is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all subjects in the group divided by the sum of the number of days on study of all subjects in the group and multiplied by 365.25. (NCT00370071)
Timeframe: Baseline up to Week 24
| Intervention | relapses per year (Number) |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | 0.38 |
Assessment of Relapses: Percentage of Relapse-free Subjects After 24 Weeks
A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical event. The abnormality must be present for at least 24 hours and occur in the absence of fever (axillary temperature >37.5 degree celsius / 99.5 degree fahrenheit) or known infection. A relapse must be confirmed by a documented report from a physician or by objective assessment. (NCT00370071)
Timeframe: After 24 weeks
| Intervention | percentage of subjects (Number) |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | 84.6 |
Number of New Gadolinium (T1)-Enhancing Lesions at Baseline, Weeks 12 and 24
"In the categories listed below, N signifies the number of subjects evaluable for the timepoints." (NCT00370071)
Timeframe: Baseline, Weeks 12 and 24
| Intervention | Lesions (Mean) |
|---|
| Baseline (N=39) | Week 12 (N=38) | Week 24 (N=37) |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | 2.8 | 0.5 | 0.8 |
Number of T2 Lesions at Baseline, Weeks 12 and 24
"In the categories listed below, N signifies the number of subjects evaluable for the timepoints." (NCT00370071)
Timeframe: Baseline, Weeks 12 and 24
| Intervention | Lesions (Mean) |
|---|
| Baseline (N=39) | Week 12 (N=38) | Week 24 (N=37) |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | 48.7 | 48.8 | 44.6 |
Difference Between the Number of Newly Active Lesions in Magnetic Resonance Imaging (MRI) Per Three Months During the 6-month Treatment Period and the Number of Newly Active Lesions During 3-month Pre-treatment
The primary efficacy variable was calculated by subtracting the number of newly active lesions during the 3-month pre-treatment period from the cumulative number of newly active lesions during the 6-month treatment period divided by 2 (number of newly active lesions per three months, new lesion frequency per 3 months) (NCT00370071)
Timeframe: after 6 months of treatment as compared to 3-month pre-treatment
| Intervention | lesions (Median) |
|---|
| Interferon Beta-1b (Betaseron, BAY86-5046) | -1.5 |
Number of Participants With a Combined Response Consisting of All Three Responses - (a) Serological Response, (b) Virological Response, and (c) Biochemical Response
"Serological response is defined as Loss of HBeAg (Hepatitis B e antigen) and Appearance of anti-HBe (Hepatitis B e antibodies); participant is HBeAg negative and anti-HBe positive.~Virological response was defined as having < 10^5 copies/mL of serum HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) by real-time PCR (Polymerase Chain Reaction).~Biochemical response was defined as acheiving normal levels of ALT (Alanine Aminotransferase) level in Units/L." (NCT00371761)
Timeframe: At Week 72 [for Pegylated interferon alfa-2b (PegIntron), at 48 weeks post PegIntron treatment for up to 24 weeks; for Adefovir, at 24 weeks post adefovir treatment for up to 48 weeks]
| Intervention | Participants (Number) |
|---|
| PegIntron | 0 |
| Adefovir | 0 |
Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir
Only subjects who received telaprevir were to be analyzed for this outcome. Maximum, minimum and average plasma concentrations observed during assessment period were reported. (NCT00372385)
Timeframe: Day 1, 4, 8, 15, 22, 29, 43, 57, 71, 85
| Intervention | nanogram per milliliter (ng/mL) (Mean) |
|---|
| Cmax | Cmin | Cavg |
|---|
| Telaprevir | 3370 | 2510 | 3055 |
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
"AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Study drug includes all investigational agents (including placebo, if applicable) administered during the course of the study." (NCT00372385)
Timeframe: Baseline up to Week 48
| Intervention | participants (Number) |
|---|
| AEs | SAEs |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 81 | 8 |
,| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | 80 | 16 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a 12 Week | 78 | 9 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | 82 | 11 |
Number of Subjects With Viral Relapse
Viral relapse was defined as having detectable HCV RNA during antiviral follow-up. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00372385)
Timeframe: After last dose of study drug up to antiviral follow-up (up to Week 72)
| Intervention | participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 10 |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | 8 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | 19 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a 12 Week | 22 |
Percentage of Subjects With Undetectable Plasma HCV RNA at Completion of Study Drug Dosing
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00372385)
Timeframe: Completion of study drug dosing (up to Week 48)
| Intervention | percentage of participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 54.9 |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | 70.4 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | 80.5 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a 12 Week | 61.5 |
Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00372385)
Timeframe: 24 weeks after the completion of study drug dosing (up to Week 72)
| Intervention | percentage of participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 46.3 |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | 69.1 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | 59.8 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a 12 Week | 35.9 |
Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00372385)
Timeframe: 12 weeks after the completion of study drug dosing (up to Week 60)
| Intervention | percentage of participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 47.6 |
| Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week | 69.1 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week | 59.8 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a 12 Week | 37.2 |
A Sustained Virologic Response (SVR), Defined as a Plasma HCV RNA Level Below the Lower Level of Quantitation (LLQ) at 24 Weeks Post-treatment
Number of participants with SVR at 24-week follow up after treatment with PEG-Intron and Ribavirin in post-orthotopic liver transplant recipients with recurrent HCV. (NCT00378599)
Timeframe: 24 weeks after completion of up to 48 weeks of therapy
| Intervention | Participants (Number) |
|---|
| PEG-Intron Plus Ribavirin | 36 |
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
"AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Study drug includes all investigational agents (including placebo, if applicable) administered during the course of the study." (NCT00420784)
Timeframe: Baseline up to 2 weeks after last dose of study drug (up to Week 50)
| Intervention | participants (Number) |
|---|
| AEs | SAEs |
|---|
| PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 Week | 111 | 9 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week | 112 | 6 |
,| Telaprevir 24 Week+Peg-IFN-alfa-2a 24 Week | 105 | 6 |
,| Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 Week | 113 | 16 |
Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir
Only subjects who received telaprevir were to be analyzed for this outcome. Maximum, minimum and average plasma concentrations observed during assessment period were reported. (NCT00420784)
Timeframe: Week 2, 4, 8, 12, 16, 24
| Intervention | nanogram per milliliter (ng/mL) (Mean) |
|---|
| Cmax | Cmin | Cavg |
|---|
| Telaprevir | 2755 | 2335 | 2610 |
Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00420784)
Timeframe: 24 weeks after the completion of study drug dosing (up to Week 72)
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week | 51.3 |
| Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 Week | 53.1 |
| Telaprevir 24 Week+Peg-IFN-alfa-2a 24 Week | 24.3 |
| PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 Week | 14.0 |
Percentage of Subjects With Undetectable Plasma HCV RNA at Completion of Study Drug Dosing
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00420784)
Timeframe: Completion of study drug dosing (up to Week 48)
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week | 75.7 |
| Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 Week | 67.3 |
| Telaprevir 24 Week+Peg-IFN-alfa-2a 24 Week | 54.1 |
| PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 Week | 29.8 |
Percentage of Subjects With Undetectable Plasma HCV RNA
"Percentage of subjects with undetectable HCV RNA at 24 weeks after last dose of study drug for treatment group PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 Week and at 48 weeks after last dose of study drug for treatment groups Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week, Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 Week and Telaprevir 24 Week+Peg-IFN-alfa-2a 24 Week were presented. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL)." (NCT00420784)
Timeframe: Up to Week 96 (24 weeks after last dose of study drug for PBO group; 48 weeks after last dose of study drug for telaprevir groups)
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week | 48.7 |
| Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 Week | 44.2 |
| Telaprevir 24 Week+Peg-IFN-alfa-2a 24 Week | 22.5 |
| PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 Week | 14.0 |
Number of Subjects With Viral Relapse
Viral relapse was defined as having detectable HCV RNA during antiviral follow-up. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00420784)
Timeframe: After last dose of study drug up to 24 week antiviral follow-up (up to Week 72)
| Intervention | participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week | 26 |
| Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 Week | 10 |
| Telaprevir 24 Week+Peg-IFN-alfa-2a 24 Week | 32 |
| PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 Week | 18 |
Number of Participants With a Sustained Virologic Response
"Participants were tested for the presence of Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) in blood by Qualitative Polymerase Chain Reaction (qPCR). If the HCV-RNA is not detectable, the participant is negative for HCV-RNA.~Sustained virologic responders were participants negative for HCV-RNA at 24 weeks following the completion of therapy. A Participant that withdrew prior to 24 weeks following the completion of therapy was considered a non-responder." (NCT00423800)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Participants (Number) |
|---|
| Responders | Non-responders |
|---|
| Pegetron® - 24 Weeks | 3 | 0 |
,| Pegetron® - 48 Weeks | 1 | 1 |
Number of Participants With a Virological Relapse
"Participants were tested for the presence of Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) in blood by Qualitative Polymerase Chain Reaction (qPCR).~Virological relapse in participants was defined as having negative virology (HCV-RNA) at end of treatment, but positive virology (HCV-RNA) again at 24 weeks of follow up post treatment." (NCT00423800)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Participants (Number) |
|---|
| Participants with Virological Relapse | Participants with No Virological Relapse |
|---|
| Pegetron® - 24 Weeks | 0 | 3 |
,| Pegetron® - 48 Weeks | 0 | 1 |
Diameter of Injection Site Redness
Blinded assessment of mean change in diameter of redness (in mm) at an injection site following an injection (NCT00428584)
Timeframe: 1-72 hours post injection over the first 12 weeks including the titration period
| Intervention | mm (Mean) |
|---|
| New Formulation of Rebif | 8.28 |
| Betaseron | 6.87 |
Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and 10 Minutes Post-injection Timepoints
A visual analog scale (VAS) ranging from 0 to 100 mm on which subjects rate pain from no pain (0 mm) to worst possible pain (100 mm) was used. Mean VAS of 21 injections for each patient at pre-injection compared to mean VAS of 21 injections for each patient 10 minutes post injection. (NCT00428584)
Timeframe: Pre-injection to 10 minutes post-injection
| Intervention | Millimeters (Mean) |
|---|
| New Formulation of Rebif | 0.70 |
| Betaseron | 1.89 |
Secondary Outcome - Extension Phase: Change in Mean VAS at Pre-injection and 10 Minutes Post Injection
(NCT00428584)
Timeframe: Pre-injection and 10 minutes post injection
| Intervention | Millimeters (Mean) |
|---|
| New Formulation of Rebif | 0.40 |
| Betaseron to the New Formulation of Rebif | 0.91 |
Number of Pain Free Patients at 30 Minutes Post-injection
"A visual analog scale (VAS) ranging from 0 to 100 mm on which subjects rate pain from no pain (0 mm) to worst possible pain (100 mm) was used.~Pain-free was defined as a VAS score of 0 for all 21 full-dose injections for the Intent-to-Treat (ITT) population." (NCT00428584)
Timeframe: 30 minutes post injection
| Intervention | Participants (Number) |
|---|
| New Formulation of Rebif | 31 |
| Betaseron | 28 |
Primary Outcome - Extension Phase: Visual Analog Scale (VAS) of Patients Reported Pain; Change in Mean VAS at Pre-injection and 30 Minutes Post Injection
(NCT00428584)
Timeframe: Pre-injection and 30 minutes post injection
| Intervention | Millimeters (Mean) |
|---|
| New Formulation of Rebif | 0.34 |
| Betaseron to the New Formulation of Rebif | 0.42 |
Secondary Outcome - Extension Phase: Diameter in Injection Site Redness
(NCT00428584)
Timeframe: 1 to 72 hours post injection
| Intervention | Millimeters (Mean) |
|---|
| New Formulation of Rebif | 10.79 |
| Betaseron to the New Formulation of Rebif | 7.46 |
Visual Analog Scale (VAS) of Patient Reported Pain: Change in Mean VAS for the 21 Full-dose Injections at Pre-injection and 30 Minutes Post-injection Timepoints
Subject reported perception of pain on the VAS where the slash drawn by the patient represents pain of increasing intensity from 0 (no pain) to 100 (worse possible pain), measured in millimeters. Mean VAS of 21 injections for each patient at pre-injection compared to mean VAS of 21 injections for each patient 30 minutes post-injection (NCT00428584)
Timeframe: From pre-injection to 30 minutes post injection of the VAS pain scores across the first 21 injections of full dose therapy of a new formulation of rebif and Betaseron
| Intervention | mm (Mean) |
|---|
| Mean Pre-Injection VAS Score | Mean VAS at 30 minutes Post-Injection | Mean Change to 30 Minutes Post-Injection |
|---|
| Betaseron | 0.40 | 1.54 | 1.14 |
,| New Formulation of Rebif | 0.43 | 1.10 | 0.67 |
Secondary Outcome - Extension Phase: Number of Pain Free Patients at 30 Minutes Post Injection
(NCT00428584)
Timeframe: Pain free patients at 30 minutes post injection
| Intervention | Participants (Number) |
|---|
| New Formulation of Rebif | 30 |
| Betaseron to the New Formulation of Rebif | 36 |
Local and/or Systemic Solicited Symptoms After Intranasal Immunization.
Number of participants (frequency) reporting solicited (systematically collected on a Memory Aid) reactogenicity events of any severity and number reporting severe occurrences. (NCT00436046)
Timeframe: 0-7 days following immunization
| Intervention | Participants (Number) |
|---|
| Elevated Oral Temperature - Any severity | Elevated Oral Temperature - Severe | Feverishness - Any severity | Feverishness - Severe | Malaise - Any severity | Malaise - Severe | Myalgia - Any severity | Myalgia - Severe | Headache - Any severity | Headache - Severe | Nausea - Any severity | Nausea - Severe | Nasal Obstruction - Any severity | Nasal Obstruction - Severe | Nasal Discharge - Any severity | Nasal Discharge - Severe | Sneezing - Any severity | Sneezing - Severe | Sore Throat - Any severity | Sore Throat - Severe | Cough - Any severity | Cough - Severe | Any systemic symptom of any severity | Severe systemic symptom | Any local symptom of any severity | Severe local symptom | Any symptom of any severity | Severe symptom |
|---|
| IVV With 10M IFN | 0 | 0 | 2 | 0 | 9 | 2 | 5 | 0 | 12 | 1 | 6 | 0 | 9 | 0 | 10 | 0 | 9 | 0 | 11 | 0 | 8 | 0 | 20 | 2 | 20 | 0 | 26 | 2 |
,| IVV With 1M IFN | 0 | 0 | 0 | 0 | 7 | 0 | 7 | 0 | 14 | 0 | 1 | 0 | 9 | 0 | 14 | 0 | 10 | 0 | 10 | 0 | 5 | 0 | 21 | 0 | 22 | 0 | 27 | 0 |
,| IVV Without IFN | 1 | 0 | 1 | 1 | 11 | 1 | 5 | 1 | 17 | 0 | 1 | 1 | 10 | 0 | 14 | 0 | 13 | 0 | 10 | 0 | 5 | 0 | 21 | 1 | 24 | 0 | 28 | 1 |
Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza A/H1N1 and A/H3N2 at 14 Days After Intranasal Immunization.
Number of subjects (frequency) responding with a four-fold or greater increase (magnitude) in titer at 14 days after immunization, relative to pre-immunization levels. (NCT00436046)
Timeframe: 14 days after immunization.
| Intervention | Participants (Number) |
|---|
| HAI - A/New Caledonia/20/99 at Day 14 | HAI - A/Wisconsin/67/2005 at Day 14 | Neutralization - A/New Caledonia/20/99 at Day 14 | Neutralization - A/Wisconsin/67/2005 at Day 14 |
|---|
| IVV With 10M IFN | 11 | 7 | 9 | 10 |
,| IVV With 1M IFN | 13 | 12 | 12 | 13 |
,| IVV Without IFN | 16 | 21 | 13 | 16 |
Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza A/H1N1 and A/H3N2 at 28 Days After Intranasal Immunization.
Number of subjects (frequency) responding with a four-fold or greater increase (magnitude) in titer at 28 days after immunization, relative to pre-immunization levels. (NCT00436046)
Timeframe: 28 days after immunization
| Intervention | Participants (Number) |
|---|
| HAI - A/New Caledonia/20/99 at Day 28 | HAI - A/Wisconsin/67/2005 at Day 28 | Neutralization - A/New Caledonia/20/99 at Day 28 | Neutralization - A/Wisconsin/67/2005 at Day 28 |
|---|
| IVV With 10M IFN | 11 | 7 | 10 | 8 |
,| IVV With 1M IFN | 14 | 20 | 15 | 13 |
,| IVV Without IFN | 17 | 23 | 17 | 17 |
Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza B at 28 Days After Intranasal Immunization.
Number of subjects (frequency) responding with a four-fold or greater increase (magnitude) in titer at 28 days after immunization, relative to pre-immunization levels. (NCT00436046)
Timeframe: 28 days after immunization
| Intervention | Participants (Number) |
|---|
| HAI - B/Malaysia/2506/2004 at Day 28 | Neutralization - B/Malaysia/2506/2004 at Day 28 |
|---|
| IVV With 10M IFN | 9 | 13 |
,| IVV With 1M IFN | 16 | 13 |
,| IVV Without IFN | 14 | 16 |
Unsolicited Adverse Events After Intranasal Immunization
Number of subjects (frequency) with spontaneous reports of Adverse Events of any severity and severe or higher severity, during the 28 days after vaccination regardless of relatedness. Events reported by more than 5.6% of subjects in any group are reported by MedDRA Preferred Term. (NCT00436046)
Timeframe: Non-serious AEs are collected through 28 days after vaccination. Serious AEs are collected through 180 days after vaccination.
| Intervention | Participants (Number) |
|---|
| Abdominal pain upper - Any severity | Abdominal pain upper - Severe | Upper respiratory tract infection - Any severity | Upper respiratory tract infection - Severe | Dysgeusia - Any severity | Dysgeusia - Severe | Pharyngolaryngeal pain - Any severity | Pharyngolaryngeal pain - Severe | Rhinorrhoea - Any severity | Rhinorrhoea - Severe | Dizziness - Any severity | Dizziness - Severe | Dysphonia - Any severity | Dysphonia - Severe | Postnasal drip - Any severity | Postnasal drip - Severe | Diarrhoea - Any severity | Diarrhoea - Severe |
|---|
| IVV With 10M IFN | 0 | 0 | 3 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 0 |
,| IVV With 1M IFN | 2 | 0 | 4 | 0 | 2 | 0 | 1 | 0 | 3 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| IVV Without IFN | 0 | 0 | 3 | 1 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 |
Serum Antibody Responses (Hemagglutination Inhibition (HAI) and Neutralization) to Influenza B at 14 Days After Intranasal Immunization.
Number of subjects (frequency) responding with a four-fold or greater increase (magnitude) in titer at 14 days after immunization, relative to pre-immunization levels. (NCT00436046)
Timeframe: 14 days after immunization
| Intervention | Participants (Number) |
|---|
| HAI - B/Malaysia/2506/2004 at Day 14 | Neutralization - B/Malaysia/2506/2004 at Day 14 |
|---|
| IVV With 10M IFN | 8 | 8 |
,| IVV With 1M IFN | 11 | 9 |
,| IVV Without IFN | 13 | 12 |
Antibody Responses in Nasal Secretions to Influenza A/H1N1 and A/H3N2 at 28 Days After Intranasal Immunization
Number of subjects (frequency) responding with a four-fold or greater increase (magnitude) in titer at day 28 after immunization, relative to pre-immunization levels. (NCT00436046)
Timeframe: 28 days after immunization.
| Intervention | Participants (Number) |
|---|
| IgG to A/New Caledonia/20/99 at Day 28 | IgA to A/New Caledonia/20/99 at Day 28 | IgG to A/Wisconsin/67/2005 at Day 28 | IgA to A/Wisconsin/67/2005 at Day 28 |
|---|
| IVV With 10M IFN | 3 | 1 | 6 | 4 |
,| IVV With 1M IFN | 1 | 1 | 3 | 3 |
,| IVV Without IFN | 3 | 3 | 4 | 3 |
Antibody Responses in Nasal Secretions to Influenza A/H1N1 and A/H3N2 at 14 Days After Intranasal Immunization.
Number of subjects (frequency) responding with a four-fold or greater increase (magnitude) in titer at day 14 after immunization, relative to pre-immunization levels (NCT00436046)
Timeframe: 14 days after immunization.
| Intervention | Participants (Number) |
|---|
| IgG to A/New Caledonia/20/99 at Day 14 | IgA to A/New Caledonia/20/99 at Day 14 | IgG to A/Wisconsin/67/2005 at Day 14 | IgA to A/Wisconsin/67/2005 at Day 14 |
|---|
| IVV With 10M IFN | 5 | 1 | 4 | 6 |
,| IVV With 1M IFN | 3 | 0 | 2 | 3 |
,| IVV Without IFN | 3 | 2 | 3 | 1 |
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
Time to first Grade 3 or 4 hematological toxicity or liver toxicity (lymphocytes, cluster of differentiation 4 (CD4+) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin) were estimated using the Kaplan-Meier method. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed. (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Months (Number) |
|---|
| 10th percentile: Lymphocytes toxicity | 20th percentile: Lymphocytes toxicity | 10th percentile: White Blood Cell toxicity | 20th percentile: White Blood Cell toxicity | 10th percentile: Neutrophil toxicity | 20th percentile: Neutrophil toxicity | 10th percentile: CD4+ count toxicity | 20th percentile: CD4+ count toxicity | 10th percentile: ALT toxicity | 20th percentile: ALT toxicity |
|---|
| Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 0.36 | 2.23 | NA | NA | 0.92 | NA | 2.96 | 7.00 | NA | NA |
Open Label Extension Period: Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure
Mean change from baseline in vital signs- systolic and diastolic blood pressure was reported. (NCT00436826)
Timeframe: Baseline, Week 72
| Intervention | Millimeter of mercury (mm*hg) (Mean) |
|---|
| Systolic Blood Pressure | Diastolic Blood Pressure |
|---|
| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 0.3 | -1.7 |
Double Blind Period: Mean Change From Baseline in Vital Signs- Weight
Mean change from baseline in vital signs- weight was reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | Kilogram (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -0.6 |
| Placebo, IFN-beta (DB Period) | -0.4 |
Open Label Extension Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval
Mean change from baseline in ECG parameters- PR, RR, QRS and OT interval was reported. (NCT00436826)
Timeframe: Baseline, Week 72
| Intervention | milliseconds (Mean) |
|---|
| PR Interval | RR Interval | QRS Interval | QT Interval |
|---|
| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | -0.0044 | 0.0643 | -0.0026 | 0.0109 |
Double Blind Period: Mean Change in New T1 Gd+ Lesions From Baseline to Week 96
Mean change in new T1 Gd+ lesions from baseline to week 96 was reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | Lesions (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -1.0 |
| Placebo, IFN-beta (DB Period) | -0.3 |
Double Blind Period: Mean Change in T1 Hypointense Lesion Volume From Baseline to Week 96
Mean change in T1 hypointense lesion volume from baseline to week 96 was reported. T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | millimeter cubic (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -481.8 |
| Placebo, IFN-beta (DB Period) | -263.0 |
Double Blind Period: Mean Change in T2 Lesion Volume From Baseline to Week 96
Mean change in T2 lesion volume From baseline to Week 96 were reported. T2 lesions were measured by using magnetic resonance imaging (MRI) scans. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | cubic millimeters (mm^3) (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -2007.2 |
| Placebo, IFN-beta (DB Period) | -1224.6 |
Double Blind Period: Mean Changes From Baseline in Hemoglobin Level to Week 96
Mean changes in hemoglobin level from baseline to week 96 was reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | gram per liter (g/L) (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -2.9 |
| Placebo, IFN-beta (DB Period) | -2.5 |
OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Percentage of participants with Grade 3 or 4 CTCAE v 4.0 toxicity on the following hematology and liver function parameters were reported: lymphocytes, cluster of differentiation 4 (CD4) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. (NCT00436826)
Timeframe: Baseline (OLEP) up to Week 96
| Intervention | Percentage of participants (Number) |
|---|
| Grade 3 or 4 Lymphocyte toxicity | Grade 3 or 4 Hemoglobin toxicity | Grade 3 or 4 White Blood Cell toxicity | Grade 3 or 4 Neutrophil toxicity | Grade 3 or 4 CD4+ toxicity | Grade 3 or 4 AST toxicity | Grade 3 or 4 ALT toxicity | Grade 3 or 4 Platelet toxicity | Grade 3 or 4 Bilirubin toxicity |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (Safety Follow up) | 3.9 | 2.0 | 0.00 | 0.00 | 14.0 | 0.00 | 0.00 | 0.00 | 0.00 |
,| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 48.9 | 0.00 | 4.3 | 6.4 | 66.0 | 0.00 | 0.00 | 0.00 | 0.00 |
,| Placebo, IFN-beta (Safety Follow up) | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
,| Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 28.6 | 0.00 | 3.6 | 14.3 | 21.4 | 0.00 | 3.6 | 0.00 | 0.00 |
Double Blind Period: Percent Change in Normalized Brain Volume From Baseline to Week 96
Brain volume was measured using magnetic resonance imaging (MRI) scans of the brain. Percent change in normalized brain volume from baseline to week 96 was reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | Percent Change (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -1.01 |
| Placebo, IFN-beta (DB Period) | -1.42 |
Double Blind Period: Percentage of Participants Qualifying Relapse-free
A qualifying relapse was defined as a 2-grade increase in 1 or more Kurtzke Functional Systems (KFS) or a 1-grade increase in 2 or more KFS, excluding changes in bowel/bladder or cognition, in the absence of fever, lasting for >= 24 hours, and preceded by at least 30 days of clinical stability or improvement. Percentage of participants qualifying relapse-free were reported. (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Percentage of Participants (Number) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 75.0 |
| Placebo, IFN-beta (DB Period) | 52.1 |
Double Blind Period: Percentage of Participants With no Active T1 Gd-Enhanced Lesions at Week 96
Percentage of participants with no active T1 Gd-enhanced lesions at week 96 were reported. Active T1 Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. (NCT00436826)
Timeframe: Week 96
| Intervention | Percentage of Participants (Number) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 86.0 |
| Placebo, IFN-beta (DB Period) | 56.3 |
Double Blind Period: Percentage of Participants With no Active T2 Lesions at Week 96
Percentage of participants with no active T2 lesions at week 96 were reported. Active T2 lesions were measured by using magnetic resonance imaging (MRI) scans. (NCT00436826)
Timeframe: Week 96
| Intervention | Percentage of Participants (Number) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 56.2 |
| Placebo, IFN-beta (DB Period) | 29.2 |
Double Blind Period: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) in Infections and Infestations System Organ Class (SOC)
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration.TEAEs were entered in infections and infestations SOC as per medical dictionary for regulatory activities (MedDRA) version 11.0 (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Percentage of participants (Number) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 61.3 |
| Placebo, IFN-beta (DB Period) | 54.2 |
OLE and Safety Follow-up Period: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) in Infections and Infestations System Organ Class (SOC)
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration.TEAEs were entered in infections and infestations SOC as per medical dictionary for regulatory activities (MedDRA) version 11.0 (NCT00436826)
Timeframe: Baseline (OLEP) up to Week 96
| Intervention | Percentage of participants (Number) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 38.3 |
| Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 21.4 |
| Cladribine 3.5 mg/kg, IFN-beta (Safety Follow up) | 11.5 |
| Placebo, IFN-beta (Safety Follow up) | 0 |
Double Blind Period: Mean Number of T1 Hypointense Lesions Per Participant Per Scan at Week 96
Mean number of T1 hypointense lesions per participant per scan at 96 weeks were reported. T1 hypointense lesions were measured by using magnetic resonance imaging (MRI) scans. (NCT00436826)
Timeframe: Week 96
| Intervention | Lesions (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 0.28 |
| Placebo, IFN-beta (DB Period) | 0.43 |
Open Label Extension Period: Mean Change From Baseline in Vital Signs- Pulse Rate
Mean change from baseline in vital signs- Pulse Rate was reported. (NCT00436826)
Timeframe: Baseline, Week 72
| Intervention | beats per minutes (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 4.7 |
OLE and Safety Follow-up Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs. (NCT00436826)
Timeframe: Baseline (OLEP) up to Week 96
| Intervention | Participants (Count of Participants) |
|---|
| Participants with TEAEs | Participants with Serious TEAEs |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (Safety Follow up) | 22 | 1 |
,| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 37 | 0 |
,| Placebo, IFN-beta (Safety Follow up) | 0 | 0 |
,| Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 19 | 1 |
Double Blind Period: Time to Recovery From Grade 3 or 4 Hematological Toxicity
"Time to recovery from grade 3 or 4 hematological were reported: lymphocytes, platelets, neutrophils, white blood cells and hemoglobin. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Recovery as Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1." (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Days (Mean) |
|---|
| Hemoglobin | White Blood Cell | Neutrophil | Lymphocyte |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 19.50 | 31.27 | 41.17 | 142.53 |
Open Label Extension Period: Mean Change From Baseline in Vital Signs- Temperature
Mean change from baseline in vital signs- temperature was reported. (NCT00436826)
Timeframe: Baseline, Week 72
| Intervention | Degree celsius (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | -0.3 |
Open Label Extension Period: Mean Change From Baseline in Vital Signs- Weight
Mean change from baseline in vital signs- weight was reported. (NCT00436826)
Timeframe: Baseline, Week 72
| Intervention | Kilogram (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | -9.4 |
Double Blind Period and OLE Period: Time to 3-Month Sustained Expanded Disability Status Scale (EDSS) Progression
EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in Multiple Sclerosis (MS). Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. Time to sustained disability progression was analyzed using a Cox proportional hazards model. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed. (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Days (Number) |
|---|
| 10th percentile | 20th percentile |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 244 | NA |
,| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 87 | 246 |
,| Placebo, IFN-beta (DB Period) | 484 | 0 |
,| Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 85 | 0 |
Double Blind Period and OLE Period: Time to First Qualifying Relapse
A qualifying relapse was defined as a 2-grade increase in at least one, or a 1-grade increase in at least two, Kurtzke Functional Systems excluding bowel/bladder or cognition changes, in the absence of fever lasting more than or equal to 24 hours, and preceded by more than or equal to 30 days of clinical stability or improvement. Time to first qualifying relapse were analyzed using a Cox proportional hazards model. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed. (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Days (Number) |
|---|
| 10th percentile | 20th percentile |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 239 | NA |
,| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 255 | 0 |
,| Placebo, IFN-beta (DB Period) | 252 | 481 |
,| Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 155 | 0 |
Double Blind Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval
Mean change from baseline in ECG parameters- PR, RR, QRS and OT interval was reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | milliseconds (Mean) |
|---|
| PR Interval | RR Interval | QRS Interval | QT Interval |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 0.0001 | 0.0361 | 0.0028 | 0.0135 |
,| Placebo, IFN-beta (DB Period) | 0.0033 | -0.0272 | 0.0043 | 0.0037 |
Double Blind Period: Maximum Corrected QT Interval (QTc)
Criteria for potential clinical concern in ECG parameters: Maximum corrected QT interval (QTc) in range of 450 to less than 480 millisecond (msec). (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Milliseconds (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 0.4381 |
| Placebo, IFN-beta (DB Period) | 0.4361 |
Double Blind Period: Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure
Mean change from baseline in vital signs- systolic and diastolic blood pressure was reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | Millimeter of mercury (mm*hg) (Mean) |
|---|
| Systolic Blood Pressure | Diastolic Blood Pressure |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -0.6 | -0.6 |
,| Placebo, IFN-beta (DB Period) | 0.0 | -2.2 |
Double Blind Period: Mean Changes From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Week 96
Mean changes in ALT and AST from baseline to week 96 were reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | Units per liter (Mean) |
|---|
| ALT | AST |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -3.0 | -1.7 |
,| Placebo, IFN-beta (DB Period) | 1.3 | 1.1 |
Double Blind Period: Mean Changes From Baseline in CD4+ Count, CD8+ Count, and CD19+ to Week 96
Mean changes CD4+ Count, CD8+ Count, and CD19+ from baseline to Week 96 were reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | Cells per microliter (Mean) |
|---|
| CD4+ | CD8+ | CD19+ |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -604.1 | -137.8 | 22.0 |
,| Placebo, IFN-beta (DB Period) | 7.1 | 23.9 | 30.7 |
Double Blind Period: Mean Changes in Lymphocytes, White Blood Cells (WBC), Neutrophils and Platelets Values From Baseline to Week 96
Mean changes in lymphocytes, WBC, neutrophils and platelets from baseline to week 96 were reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | 10^9 cells per liter (Mean) |
|---|
| Lymphocytes | Platelet | WBC | Neutrophils |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -0.8 | -29.8 | -1.5 | -0.7 |
,| Placebo, IFN-beta (DB Period) | 0.0 | -12.4 | -0.4 | -0.4 |
Double Blind Period: Number of Combined Unique Active (CUA) Lesions, Active Time Constant 2 (T2) Lesions, and Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan
Number of CUA lesions, active T2 lesions, and T1 Gd+ lesions were measured by using magnetic resonance imaging (MRI) scans. (NCT00436826)
Timeframe: Week 96
| Intervention | Lesions (Mean) |
|---|
| T1 Gd+ lesions | CUA lesions | T2 lesions |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 0.06 | 0.55 | 0.53 |
,| Placebo, IFN-beta (DB Period) | 0.34 | 1.12 | 1.04 |
Double Blind Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs. (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Participants (Count of Participants) |
|---|
| Participants with TEAEs | Participants with Serious TEAEs |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 119 | 12 |
,| Placebo, IFN-beta (DB Period) | 36 | 5 |
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
Time to first Grade 3 or 4 hematological toxicity or liver toxicity (lymphocytes, cluster of differentiation 4 (CD4) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin) were estimated using the Kaplan-Meier method. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed. (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Months (Number) |
|---|
| 10th percentile: Lymphocytes toxicity | 20th percentile: Lymphocytes toxicity | 10th percentile:Hemoglobin toxicity | 20th percentile:Hemoglobin toxicity | 10th percentile: White Blood Cell toxicity | 20th percentile: White Blood Cell toxicity | 10th percentile: Neutrophil toxicity | 20th percentile: Neutrophil toxicity | 10th percentile: CD4+ count toxicity | 20th percentile: CD4+ count toxicity | 10th percentile: AST toxicity | 20th percentile: AST toxicity | 10th percentile: ALT toxicity | 20th percentile: ALT toxicity |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 1.61 | 2.00 | NA | NA | 17.74 | NA | 12.55 | NA | 1.87 | 2.99 | NA | NA | NA | NA |
Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
Time to first Grade 3 or 4 hematological toxicity or liver toxicity (lymphocytes, cluster of differentiation 4 (CD4) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin) were estimated using the Kaplan-Meier method. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed. (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Months (Number) |
|---|
| 10th percentile: Lymphocytes toxicity | 20th percentile: Lymphocytes toxicity | 10th percentile: Neutrophil toxicity | 20th percentile: Neutrophil toxicity | 10th percentile: CD4+ count toxicity | 20th percentile: CD4+ count toxicity | 10th percentile: ALT toxicity | 20th percentile: ALT toxicity |
|---|
| Placebo, IFN-beta (DB Period) | NA | NA | NA | NA | NA | NA | NA | NA |
Double Blind Period: Time to Recovery From Grade 3 or 4 Hematological Toxicity
"Time to recovery from grade 3 or 4 hematological were reported: lymphocytes, platelets, neutrophils, white blood cells and hemoglobin. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Recovery as Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1." (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Days (Mean) |
|---|
| Neutrophil | Lymphocyte |
|---|
| Placebo, IFN-beta (DB Period) | 56.75 | 28.00 |
Open Label Extension Period: Maximum Corrected QT Interval (Qtc)
Criteria for potential clinical concern in ECG parameters: Maximum corrected QT interval (QTc) in range of 450 to less than 480 millisecond (msec). (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Milliseconds (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 0.4370 |
| Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 0.4317 |
Double Blind Period: Mean Change From Baseline in Vital Signs- Temperature
Mean change from baseline in vital signs- temperature was reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | Degree celsius (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -0.1 |
| Placebo, IFN-beta (DB Period) | -0.1 |
Open Label Extension Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- Heart Rate
Mean change from baseline in ECG parameters- Heart Rate was reported. (NCT00436826)
Timeframe: Baseline, Week 72
| Intervention | beats per minutes (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | -4.889 |
Double Blind Period: Annualized Qualifying Relapse Rate
A qualifying relapse was defined as a 2-grade increase in at least one, or a 1-grade increase in at least two, Kurtzke Functional Systems excluding bowel/bladder or cognition changes, in the absence of fever lasting more than or equal to 24 hours, and preceded by more than or equal to 30 days of clinical stability or improvement. The annualized relapse rate for each treatment group was the mean of the annualized relapse rates for all the participants in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | relapses per year (Number) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 0.12 |
| Placebo, IFN-beta (DB Period) | 0.32 |
Double Blind Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- Heart Rate
Mean change from baseline in ECG parameters- Heart Rate was reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | beats per minutes (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | -3.114 |
| Placebo, IFN-beta (DB Period) | 1.981 |
Double Blind Period: Mean Change From Baseline in Vital Signs- Pulse Rate
Mean change from baseline in vital signs- Pulse Rate was reported. (NCT00436826)
Timeframe: Baseline, Week 96
| Intervention | beats per minutes (Mean) |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 1.0 |
| Placebo, IFN-beta (DB Period) | 0.4 |
Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity
Time to first Grade 3 or 4 hematological toxicity or liver toxicity (lymphocytes, cluster of differentiation 4 (CD4+) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin) were estimated using the Kaplan-Meier method. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed. (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Months (Number) |
|---|
| 10th percentile: Lymphocytes toxicity | 20th percentile: Lymphocytes toxicity | 10th percentile: White Blood Cell toxicity | 20th percentile: White Blood Cell toxicity | 10th percentile: Neutrophil toxicity | 20th percentile: Neutrophil toxicity | 10th percentile: CD4+ count toxicity | 20th percentile: CD4+ count toxicity |
|---|
| Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext) | 0.30 | 1.64 | NA | NA | NA | NA | 0.92 | 0.99 |
Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity
Percentage of participants with Grade 3 or 4 CTCAE v 4.0 toxicity on the following hematology and liver function parameters were reported: lymphocytes, cluster of differentiation 4 (CD4) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. (NCT00436826)
Timeframe: Baseline up to Week 96
| Intervention | Percentage of participants (Number) |
|---|
| Grade 3 or 4 Lymphocyte toxicity | Grade 3 or 4 Hemoglobin toxicity | Grade 3 or 4 White Blood Cell toxicity | Grade 3 or 4 Neutrophil toxicity | Grade 3 or 4 CD4+ toxicity | Grade 3 or 4 AST toxicity | Grade 3 or 4 ALT toxicity | Grade 3 or 4 Platelet toxicity | Grade 3 or 4 Bilirubin toxicity |
|---|
| Cladribine 3.5 mg/kg, IFN-beta (DB Period) | 63.71 | 2.42 | 10.48 | 12.10 | 50.81 | 0.81 | 0.81 | 0.00 | 0.00 |
,| Placebo, IFN-beta (DB Period) | 2.08 | 0.00 | 0.00 | 2.08 | 2.08 | 0.00 | 2.08 | 0.00 | 0.00 |
Investigator Assessment Regarding Global Oral Changes.
"Number of subjects with improvement from baseline to week 24 in global oral health as rated by the attending investigator. Scale was subjective with 3 choices: improved, worsened, or unchanged." (NCT00454181)
Timeframe: 24 weeks, from baseline to the end of treatment
| Intervention | participants (Number) |
|---|
| IFN Lozenges | 9 |
| Placebo Lozenges | 2 |
Total Surface Area of the Lips Covered by Warts
Number of subjects with a 75% or greater decrease from baseline to week 24 in total lip wart area (NCT00454181)
Timeframe: 24 weeks, from baseline to the end of treatment
| Intervention | participants (Number) |
|---|
| IFN Lozenges | 5 |
| Placebo Lozenges | 0 |
Subject Questionnaire Regarding Global Oral Changes
"Number of subjects reporting change in global oral health from baseline to week 24 as better. Scale was subjective with 3 choices: better, worse, or unchanged." (NCT00454181)
Timeframe: 24 weeks, from baseline to end of treatment
| Intervention | participants (Number) |
|---|
| IFN Lozenges | 14 |
| Placebo Lozenges | 2 |
Investigator Assessment Regarding Changes in Warts
"Number of subjects with improvement in oral warts from baseline to week 24 as rated by the attending investigator. Scale was subjective with 3 choices: improved, worsened, or unchanged." (NCT00454181)
Timeframe: 24 weeks, from baseline to the end of treatment
| Intervention | participants (Number) |
|---|
| IFN Lozenges | 13 |
| Placebo Lozenges | 5 |
Change in Total Oral Mucosal Area Covered by Warts.
Number of subjects with a 75% or greater decrease from baseline to week 24 in total oral wart area (NCT00454181)
Timeframe: 24 weeks, from baseline to the end of treatment
| Intervention | participants (Number) |
|---|
| IFN Lozenges | 11 |
| Placebo Lozenges | 2 |
Subject Questionnaire Regarding Changes in Warts
"Number of subjects reporting change in oral warts from baseline to week 24 as better. Scale was subjective with 3 choices: better, worse, or unchanged." (NCT00454181)
Timeframe: 24 weeks, from baseline to the end of treatment
| Intervention | participants (Number) |
|---|
| IFN Lozenges | 18 |
| Placebo Lozenges | 4 |
Liver Enzyme Elevations
"The variable Liver enzyme elevations will consist of a combination of MedDRA terms (Preferred Terms only) indicative for this condition." (NCT00459667)
Timeframe: 309 days
| Intervention | Percentage of participants (Number) |
|---|
| GGT increased | AST increased | ALT increased |
|---|
| IFNB-1b 250 mcg | 1.2 | 1.4 | 1.7 |
,| IFNB-1b 250 mcg* | 3.9 | 3.9 | 4.4 |
,| IFNB-1b 500 mcg | 2.7 | 2.0 | 2.6 |
Percentage of Patients With Neutralizing Antibody Titer to IFNB-1b of Different Cut-off Values
Serum samples of about 8 mL for analysis of neutralizing antibodies (NAbs) to interferon (IFN) beta-1b were drawn at Baseline, Week 26 and the EOS visit. (NCT00459667)
Timeframe: 309 days
| Intervention | Percentage of participants (Number) |
|---|
| NAbs titer, cut-off value 20 NU/ml | NAbs titer, cut-off value 100 NU/ml | NAbs titer, cut-off value 400 NU/ml |
|---|
| IFNB-1b 250 mcg | 21.7 | 12.4 | 6.1 |
,| IFNB-1b 250 mcg* | 16.6 | 2.5 | 0 |
,| IFNB-1b 500 mcg | 26.6 | 16.5 | 10.8 |
Flu-like-syndrome
"The variable Flu-like-syndrome will consist of a combination of MedDRA terms (Preferred Terms and Lower Level Terms) indicative for this condition." (NCT00459667)
Timeframe: 309 days
| Intervention | Percentage of participants (Number) |
|---|
| IFNB-1b 500 mcg | 17.4 |
| IFNB-1b 250 mcg | 15.8 |
| IFNB-1b 250 mcg* | 31.1 |
Injection-site Reactions
"The variable Injection-site reactions will consist of a combination of MedDRA terms (Preferred Terms only) indicative for this condition." (NCT00459667)
Timeframe: 309 days
| Intervention | Percentage of participants (Number) |
|---|
| IFNB-1b 500 mcg | 31.7 |
| IFNB-1b 250 mcg | 26.2 |
| IFNB-1b 250 mcg* | 31.7 |
Hematological Abnormalities
"The variable Hematological abnormalities will consist of a combination of MedDRA terms (Preferred Terms only) indicative for this condition." (NCT00459667)
Timeframe: 309 days
| Intervention | Percentage of participants (Number) |
|---|
| White blood cells decreased | Neutrophil count decreased | Lymphocyte count decreased | Platelet count decreased | Hemoglobin decreased |
|---|
| IFNB-1b 250 mcg | 1.9 | 1.2 | 0.6 | 0.2 | 1.1 |
,| IFNB-1b 250 mcg* | 1.7 | 2.2 | 0 | 0.6 | 0 |
,| IFNB-1b 500 mcg | 0.5 | 0.5 | 1.5 | 0.7 | 1.2 |
Number of Participants With Overall Response as Measured by RECIST Criteria
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response = CR + PR (NCT00467077)
Timeframe: After 2 cycles of treatment, up to 2 years.
| Intervention | participants (Number) |
|---|
| Gefitinib and PEG-IFNa Treatment | 2 |
Overall Survival
Estimated using the product-limit method of Kaplan and Meier. (NCT00467077)
Timeframe: Up to 5 years.
| Intervention | Months (Median) |
|---|
| Gefitinib and PEG-IFNa Treatment | 13.6 |
Progression-Free Survival
Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00467077)
Timeframe: Until disease progression, up to 5 years.
| Intervention | Months (Median) |
|---|
| Gefitinib and PEG-IFNa Treatment | 5.2 |
Six-month Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions (NCT00467077)
Timeframe: From the date treatment started until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
| Intervention | percentage of participants (Number) |
|---|
| Gefitinib and PEG-IFNa Treatment | 29 |
Toxicity as Measured by Number of Participants Who Discontinued Treatment Due to Adverse Events
Number of participants who discontinued the protocol due to adverse events. (NCT00470093)
Timeframe: Up to 5 months
| Intervention | Participants (Count of Participants) |
|---|
| Interleukin-6 and Interferon-α | 2 |
Response Rate as Assessed by Number of Participants With Partial or Complete Response by Bladé Criteria.
Number of participants with partial or complete response by Bladé criteria where partial response is defined as a >= 50% decrease in serum paraprotein or 90% decrease in urinary light chains (for participants without measurable serum paraprotein). Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells. (NCT00470093)
Timeframe: Up to 5 months
| Intervention | Participants (Count of Participants) |
|---|
| Interleukin-6 and Interferon-α | 0 |
Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F)
"End of treatment response (ETR) was defined as Success if the HCV-RNA levels were <15 IU/mL at the end of treatment. Early virological response (EVR) was defined as >=2 log10 decrease in serum HCV RNA or undetectable serum HCV RNA (<15 IU/mL) at Week 12. Complete EVR was defined as Success, if the HCV-RNA levels were <15 IU/mL at Week 12. Partial EVR was defined as Success, if there was a >=2 log10 drop in HCV-RNA at Week 12 compared to baseline but with a level that was still >=15 IU/mL at that time point." (NCT00483938)
Timeframe: Week 12 (Groups C, D, E, and F), and end of treatment (Weeks 48, 72, 36, 48, 24, and 48 for Groups A, B, C, D, E, and F, respectively)
| Intervention | percentage of participants (Number) |
|---|
| ETR | Complete EVR | Partial EVR |
|---|
| Pegylated-interferon Alfa-2a + Ribavirin (Group A) | 80.5 | 0 | 0 |
,| Pegylated-interferon Alfa-2a + Ribavirin (Group B) | 76.7 | 0 | 0 |
,| Pegylated-interferon Alfa-2a + Ribavirin (Group C) | 96.7 | 93.3 | 0 |
,| Pegylated-interferon Alfa-2a + Ribavirin (Group D) | 90.3 | 96.8 | 3.2 |
,| Pegylated-interferon Alfa-2a + Ribavirin (Group E) | 92.0 | 88.0 | 0 |
,| Pegylated-interferon Alfa-2a + Ribavirin (Group F) | 100.0 | 92.0 | 0 |
Percentage of Participants With Sustained Virological Response (SVR) (Groups A and B)
SVR was defined as success if the participant had HCV RNA levels <15 IU/mL as measured by COBAS AmpliPrep/COBAS TaqMan® HCV test at the 24-week untreated follow-up visit (HCV-RNA levels obtained at least 18 weeks after last dose of either pegylated-Interferon alfa-2a or ribavirin were considered if the 24-week untreated follow-up visit data were missing). Percentage of participants with SVR for Groups A and B was reported in this analysis. (NCT00483938)
Timeframe: At 24-week untreated follow-up visit (up to 72 weeks for Group A, up to 96 weeks for Group B)
| Intervention | percentage of participants (Number) |
|---|
| Pegylated-interferon Alfa-2a + Ribavirin (Group A) | 48.8 |
| Pegylated-interferon Alfa-2a + Ribavirin (Group B) | 39.5 |
Percentage of Participants With SVR (Groups C, D, E, and F)
SVR was defined as success if the participant had HCV RNA levels <15 IU/mL as measured by COBAS AmpliPrep/COBAS TaqMan® HCV test at the 24-week untreated follow-up visit (HCV-RNA levels obtained at least 18 weeks after last dose of either pegylated-Interferon alfa-2a or ribavirin were considered if the 24-week untreated follow-up visit data were missing). Percentage of participants with SVR for Groups C, D, E, and F was reported in this analysis. (NCT00483938)
Timeframe: At 24-week untreated follow-up visit (up to 60, 72, 48, and 72 weeks for Groups C, D, E, and F, respectively)
| Intervention | percentage of participants (Number) |
|---|
| Pegylated-interferon Alfa-2a + Ribavirin (Group C) | 73.3 |
| Pegylated-interferon Alfa-2a + Ribavirin (Group D) | 74.2 |
| Pegylated-interferon Alfa-2a + Ribavirin (Group E) | 84.0 |
| Pegylated-interferon Alfa-2a + Ribavirin (Group F) | 84.0 |
Annualized Relapse Rate [ARR]: Poisson Regression Estimates
"ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations.~Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale [EDSS] score or Functional System scores.~To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as offset variable; treatment group, region of enrollment and IFN-β dose level as covariates)." (NCT00489489)
Timeframe: 24 weeks
| Intervention | relapses per year (Number) |
|---|
| Placebo + IFN-β | 0.260 |
| Teriflunomide 7 mg + IFN-β | 0.280 |
| Teriflunomide 14 mg + IFN-β | 0.109 |
Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)
"Total lesion volume is the sum of the total volume of all T2-lesions and the total volume of all T1-hypointense post-gadolinium lesions measured through T2/proton density scan analysis and gadolinium-enhanced T1 scan analysis.~Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on cubic root transformed volume data (treatment group, region of enrollment, IFN-β dose level, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors)." (NCT00489489)
Timeframe: baseline (before randomization) and 24 weeks
| Intervention | mililiters (Least Squares Mean) |
|---|
| Placebo + IFN-β | -0.001 |
| Teriflunomide 7 mg + IFN-β | 0.002 |
| Teriflunomide 14 mg + IFN-β | -0.028 |
Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)
"Number of Gd-enhancing T1-lesions per scan is obtained from the total number of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study.~To account for the different number of scans among participants, a Poisson regression model with robust error variance was used (total number of Gd-enhancing T1-lesions as response variable; log-transformed number of scans as offset variable; treatment group, region of enrollment, IFN-β dose level and baseline number of Gd-enhancing T1-lesions as covariates)." (NCT00489489)
Timeframe: 24 weeks
| Intervention | lesions per scan (Number) |
|---|
| Placebo + IFN-β | 0.570 |
| Teriflunomide 7 mg + IFN-β | 0.099 |
| Teriflunomide 14 mg + IFN-β | 0.089 |
Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan
Total volume of Gd-enhancing T1-lesions per scan is obtained from the sum of the volumes of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study. (NCT00489489)
Timeframe: 24 weeks
| Intervention | mililiters per scan (Number) |
|---|
| Placebo + IFN-β | 0.068 |
| Teriflunomide 7 mg + IFN-β | 0.022 |
| Teriflunomide 14 mg + IFN-β | 0.024 |
Pharmacokinetic [PK]: Teriflunomide Plasma Concentration
Plasma concentrations of teriflunomide were measured using validated liquid chromatography-tandem mass spectrometry methods. (NCT00489489)
Timeframe: 24 weeks
| Intervention | micrograms/mililiter (μg/mL) (Mean) |
|---|
| Teriflunomide 7 mg + IFN-β | 21.437 |
| Teriflunomide 14 mg + IFN-β | 47.761 |
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA)
"PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review.~Hepatic parameters thresholds were defined as follows:~Alanine Aminotransferase [ALT] >3, 5, 10 or 20 Upper Normal Limit [ULN];~Aspartate aminotransferase [AST] >3, 5, 10 or 20 ULN;~Alkaline Phosphatase >1.5 ULN;~Total Bilirubin [TB] >1.5 or 2 ULN;~ALT >3 ULN and TB >2 ULN;" (NCT00489489)
Timeframe: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
| Intervention | participants (Number) |
|---|
| ALT >3 ULN | - ALT >5 ULN | AST >3 ULN | - AST >5 ULN | Alkaline Phosphatase >1.5 ULN | TB >1.5 ULN | ALT >3 ULN and TB >2 ULN |
|---|
| Placebo + IFN-β | 2 | 1 | 1 | 1 | 1 | 0 | 0 |
,| Teriflunomide 14 mg + IFN-β | 2 | 1 | 1 | 0 | 0 | 0 | 0 |
,| Teriflunomide 7 mg + IFN-β | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Overview of Adverse Events [AE]
AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. (NCT00489489)
Timeframe: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
| Intervention | participants (Number) |
|---|
| Any AE | - serious AE | - AE leading to death | - AE leading to study drug discontinuation |
|---|
| Placebo + IFN-β | 35 | 1 | 0 | 1 |
,| Teriflunomide 14 mg + IFN-β | 32 | 0 | 0 | 1 |
,| Teriflunomide 7 mg + IFN-β | 33 | 2 | 0 | 1 |
Overview of AE With Potential Risk of Occurrence
"AE with potential risk of occurrence were defined as follows:~Hepatic disorders;~Immune effects, mainly effects on bone marrow and infection;~Pancreatic disorders;~Malignancy;~Skin disorders, mainly Hair loss and Hair thinning;~Pulmonary disorders;~Hypertension;~Peripheral neuropathy;~Psychiatric disorders;~Hypersensitivity." (NCT00489489)
Timeframe: from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
| Intervention | participants (Number) |
|---|
| Any AE with potential risk of occurence | - Hepatic disorder AE | - Pancreatic disorder AE | - Pulmonary disorder AE | - Immune effects related AE | - Hair loss / Hair thinning AE | - Hypertension-related AE | - Peripheral neuropathy AE | - Hypersensitivity AE | - Malignancy AE | - Psychiatric disorder AE |
|---|
| Placebo + IFN-β | 24 | 5 | 5 | 0 | 13 | 0 | 1 | 4 | 5 | 0 | 0 |
,| Teriflunomide 14 mg + IFN-β | 26 | 11 | 7 | 0 | 19 | 3 | 4 | 3 | 3 | 0 | 0 |
,| Teriflunomide 7 mg + IFN-β | 25 | 8 | 2 | 0 | 18 | 3 | 0 | 1 | 3 | 0 | 0 |
Number of Participants With Histologic Response(HR)
Number of participants with histologic response (HR): number of patients who had improvement of as least 2 scores at the end of follow-up liver biopsy compared to baseline liver biopsy by Ishak scoring system (the sum of Ishak necroinflammation score (0-18) and Ishak fibrosis score (0-6); the higher the total scores, the severer the histologic changes) (NCT00491179)
Timeframe: 1.5 year
| Intervention | Participants (Number) |
|---|
| Pegylated Interferon and Ribavirin for 48 Weeks (Genotype 1) | 11 |
| Pegylated Interferon and Ribavirin for 24 Weeks (Genotype 2) | 6 |
1.Number of Participants With Sustained Virologic Response (SVR) 2.Number of Participants Who Droppoed Out of the Study Prematurely Due to Adverse Events (AEs)
"Number of participants with sustained virologic response (SVR): number of patients with undetectable HCV RNA 6 months off therapy by real-time PCR test (Cobas TaqMan HCV Test v2.0, Roche Diagnostics GmbH, Mannheim, Germany, limit of detection < 25 IU/mL)~Number of participants who droppoed out of the study prematurely due to adverse events (AEs): number of patients who prematurely withdrew from the study due to any adverse events" (NCT00491179)
Timeframe: 1.5 year
| Intervention | Participants (Number) |
|---|
| Sustained virologic response (SVR) | Drop-out |
|---|
| Pegylated Interferon and Ribavirin for 24 Weeks (Genotype 2) | 8 | 2 |
,| Pegylated Interferon and Ribavirin for 48 Weeks (Genotype 1) | 13 | 7 |
Sustained Virologic Response (SVR)Rate
(NCT00491244)
Timeframe: 1.5 year
| Intervention | participants (Number) |
|---|
| Peginterferon and Ribavirin | 130 |
| Peginterferon | 72 |
Sustained Virological Response (PCR 24 Weeks After End of Treatment)
Sustained virological response (SVR) was defined as undetectable HCV RNA in serum at the end of follow-up (24 weeks after end of therapy) according to a polymerase chain reaction (PCR) assay. (NCT00493805)
Timeframe: Up to 24 weeks following 48 or 72 weeks of therapy
| Intervention | Participants (Number) |
|---|
| Non Interventional Arm HOMA IR <= 2 | 1 |
| Interventional Arm HOMA IR > 2 | 3 |
Early Virological Response in Participants With and Without Insulin Resistance
Early Virological Response (EVR) defined as HCV PCR at Week 12 either negative or at least 2 log units less than baseline in participants with and without insulin resistance. (NCT00493805)
Timeframe: At Week 12 (after start of therapy)
| Intervention | Participants (Number) |
|---|
| Non Interventional Arm HOMA IR <= 2 | 10 |
| Interventional Arm HOMA IR > 2 | 24 |
Sustained Biochemical Response
Sustained biochemical response (SBR): alanine aminotransferase (ALT) normalization (NCT00495131)
Timeframe: 18 months
| Intervention | Participants (Number) |
|---|
| Peginterferon and Ribavirin (24 Weeks) | 75 |
| Peginterferon and Ribavirin (48 Weeks) | 107 |
Sustained Virologic Response
Undetectable HCV RNA 6 months off therapy (NCT00495131)
Timeframe: 18 months
| Intervention | participants (Number) |
|---|
| Peginterferon and Ribavirin (24 Weeks) | 87 |
| Peginterferon and Ribavirin (48 Weeks) | 117 |
Histologic Response
Histologic response: improvement of at least 2 grade of scores by Ishak liver histologic classification by end of follow up liver biopsy to baseline liver biopsy (NCT00495131)
Timeframe: 18 months
| Intervention | Participants (Number) |
|---|
| Peginterferon and Ribavirin (24 Weeks) | 71 |
| Peginterferon and Ribavirin (48 Weeks) | 97 |
Number of Patients With Response
Per World Health Organization (WHO) Tumor Response: Complete Response (CR), Partial Response (PR) or Progressive Disease (PD). CR defined as disappearance of all target lesions, PR as > = 30% decrease in sum of longest dimensions of target lesions with reference baseline sum longest dimensions and if CA 125 levels declined by >50%, provided target lesion size did not increase by >20% on imaging, and PD as >20% increase in sum of longest dimensions of target lesions taking as references smallest sum of longest dimensions recorded since treatment started, or appearance of 1 or > new lesions. (NCT00501644)
Timeframe: Follow up CT scans after every 3 courses of treatment and following completion of all treatments.
| Intervention | Participants (Number) |
|---|
| Complete Response | Partial Response | Progressive Disease |
|---|
| Chemoimmunotherapy | 9 | 21 | 24 |
MRI Parameter- Percent Brain Volume Change for 2 Years
Baseline MRI is compared to MRI images collected during subsequent timepoints. The percent brain volume change is measured using SIENAX (Structural Image Evaluation using Normalization of Atrophy-X) (NCT00501943)
Timeframe: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24
| Intervention | percent change per year (Mean) |
|---|
| Riluzole | -0.862 |
| Placebo | -0.49 |
Changes in Symbol Digit Modality Test (SDMT)
Baseline SDMT data were compared to SDMT data collected during the timepoints. A simple substitution task, the SDMT gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The total score is the total number of correctly completed boxes in the time allowed. The test score range is from 0(worst outcome) to 110 (best outcome). (NCT00501943)
Timeframe: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24
| Intervention | percent change per year (Mean) |
|---|
| Riluzole | 0.342 |
| Placebo | 0.417 |
Changes in Normalized Grey Matter Volume
The baseline data of grey matter volume obtained from the MRI images is compared to data obtained at time points using SIENA (Structural Image Evaluation using Normalization of Atrophy) and SIENAX (NCT00501943)
Timeframe: Baseline, Month-3, Month-6, Month-12 and Month-24
| Intervention | percent change per year (Mean) |
|---|
| Riluzole | -14.369 |
| Placebo | -18.444 |
Changes in MS Functional Composite (MSFC)
Baseline MSFC data is compared to MSFC data collected during the timepoints. The MSFC is a three-part, standardized, quantitative, assessment instrument that measures the clinical dimensions of leg function, arm/hand function and cognitive function and the components include Timed 25-Foot walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test. (NCT00501943)
Timeframe: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24
| Intervention | percent change per year (Mean) |
|---|
| Riluzole | 0.041 |
| Placebo | 0.052 |
Changes in Normalized White Matter Volumes (nWMV)
The baseline data of white matter volume obtained from the MRI images is compared to data obtained at time points using SIENA (Structural Image Evaluation using Normalization of Atrophy) and SIENAX (NCT00501943)
Timeframe: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24
| Intervention | percent change per year (Mean) |
|---|
| Riluzole | -1.75 |
| Placebo | -9.69 |
Changes in Peripapillary Retinal Nerve Fiber Layer Thickness (RNFL)
Baseline RNFL data is compared to the RNFL data collected during the timepoint, and the changes in RNFL is measured using optical coherence tomography (OCT). (NCT00501943)
Timeframe: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24
| Intervention | percent change per year (Mean) |
|---|
| Riluzole | -4.670 |
| Placebo | -1.839 |
Time to Progression (TTP)
TTP defined as the time from date of first dose of study medication to first documentation of objective tumor progression in days. Response evaluation by Response Evaluation Criteria in Solid Tumors (RECIST) done following 2 cycles and 3 cycles. Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline. (NCT00505635)
Timeframe: Following two 21 day cycles until disease progression
| Intervention | days (Geometric Mean) |
|---|
| Biochemotherapy With Temozolomide | 93.2 |
PFS - Time to Event
PFS was defined as the time in days from the date of treatment start to the date of first documented disease progression or death. Disease progression was evaluated according to RECIST using CT scans (preferred method), MRI scans, X-ray, bone scans, or clinical examination. Median PFS was estimated using the Kaplan-Meier method (NCT00520403)
Timeframe: Days 0, 91, 182, 273, 365, 456, and 547
| Intervention | days (Median) |
|---|
| Bevacizumab + IFN/Vinblastine | 274 |
Percentage of Participants With Disease Progression or Death
Disease progression was evaluated according to the Response Evaluation Criteria In Solid Tumors (RECIST) using computed tomography (CT) scans (preferred method), magnetic resonance imaging (MRI) scans, X-ray, bone scans, or clinical examination. (NCT00520403)
Timeframe: Days 0, 91, 182, 273, 365, 456, and 547
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab + IFN/Vinblastine | 66.9 |
Percentage of Participants With Objective Response (OR)
Percentage of participants with OR based on assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to RECIST. (NCT00520403)
Timeframe: Baseline and Cycles 3, 6, 9, 13, and 17
| Intervention | percentage of participants (Number) |
|---|
| Week 9 (n=14) | Week 18 (n=16) | Week 27 (n=16) | Week 39 (n=16) | Week 51 (n=16) |
|---|
| Bevacizumab + IFN/Vinblastine | 21.4 | 31.3 | 37.5 | 31.3 | 31.3 |
Overall Survival (OS)
OS was defined as the duration from treatment start to death from any cause. Overall survival was censored at the last contact for surviving participants and missing data points. (NCT00520403)
Timeframe: Baseline, Day 1 of every cycle to disease progression or death (up to Week 102)
| Intervention | weeks (Median) |
|---|
| Bevacizumab + IFN/Vinblastine | NA |
Annualized Relapse Rate
Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated through negative binomial regression with robust variance estimation and covariate adjustment for geographic region using observed number of relapses as dependent variable, the log total amount of follow-up from date of first study treatment for each participant as an offset variable, and treatment group and geographic region as model covariates. (NCT00530348)
Timeframe: Up to 2 years
| Intervention | relapses per participant per year (Number) |
|---|
| Interferon Beta-1a | 0.39 |
| Alemtuzumab | 0.18 |
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2
EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS). Change was calculated by subtracting Baseline value from value at Year 2. (NCT00530348)
Timeframe: Baseline, Year 2
| Intervention | units on a scale (Mean) |
|---|
| Interferon Beta-1a | -0.2 |
| Alemtuzumab | -0.2 |
Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2
Percent change in MS lesion volume as measured by MRI-T2 scan was calculated from MRI-T2-weighted scans as the following: (lesion volume at 2 years - lesion volume at Baseline)*100/ (lesion volume at Baseline). (NCT00530348)
Timeframe: Baseline, Year 2
| Intervention | percent change (Mean) |
|---|
| Interferon Beta-1a | -6.68 |
| Alemtuzumab | -10.28 |
Percentage of Participants Who Were Relapse Free at Year 2
Participants were considered relapse free at Year 2 if they did not experience a relapse from the date of first study treatment to study completion at 24 months. Percentage of participants who were relapse free at Year 2, estimated using the KM method, was reported. (NCT00530348)
Timeframe: Year 2
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a | 58.69 |
| Alemtuzumab | 77.59 |
Percentage of Participants With Sustained Accumulation of Disability (SAD)
EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with a Baseline score of 1.0 or more; and the increase persisted for at least next 2 scheduled assessments, that is, 6 consecutive months. Onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Percentage of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported. (NCT00530348)
Timeframe: Up to 2 years
| Intervention | percentage of participants with SAD (Number) |
|---|
| Interferon Beta-1a | 11.12 |
| Alemtuzumab | 8.00 |
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2
MSFC is a multidimensional measure consisting of quantitative tests of ambulation (Timed 25-Foot Walk), manual dexterity (9-Hole Peg Test; 9HPT), and cognitive function (Paced Auditory Serial Addition Test; PASAT). The MSFC score was calculated as the mean of the Z-scores of the 3 components. A Z-score was calculated by subtracting the mean of the reference population from the test result, then dividing by the standard deviation of the reference population. Higher Z-scores reflected better neurological function and a positive change from Baseline indicates improvement. An increase in score indicated an improvement (Z-score range: -3 to +3). Acquisition of disability was measured by change from Baseline in MSFC score at Year 2. (NCT00530348)
Timeframe: Baseline, Year 2
| Intervention | Z-score (Mean) |
|---|
| Baseline (n=186, 375) | Change at Year 2 (n=172, 362) |
|---|
| Alemtuzumab | -0.02 | 0.15 |
,| Interferon Beta-1a | 0.05 | 0.07 |
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
"AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Study drug includes all investigational agents (including placebo, if applicable) administered during the course of the study." (NCT00535847)
Timeframe: Baseline through Week 48
| Intervention | participants (Number) |
|---|
| AEs | SAEs |
|---|
| Other | 2 | 1 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week | 77 | 7 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | 31 | 3 |
Percentage of Subjects With End of Treatment Response
Subjects were considered to have an end of treatment response if they completed the assigned treatment regimen and had undetectable HCV RNA at end of treatment or prematurely discontinued the assigned treatment regimen and had undetectable HCV RNA at the time of discontinuation. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00535847)
Timeframe: End of treatment (up to Week 48)
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week | 72.8 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | 64.7 |
| Other | 100.0 |
Percentage of Subjects With Undetectable HCV RNA at Week 48 After Completion of Treatment Among Subjects Who Completed Assigned Treatment
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00535847)
Timeframe: 48 weeks after completion of treatment (up to Week 96)
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week | 83.1 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | 70.0 |
Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Treatment
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00535847)
Timeframe: 24 weeks after the completion of treatment (up to Week 72)
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week | 60.5 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | 52.9 |
| Other | 100.0 |
Percentage of Prior Relapsers With Undetectable HCV RNA
Prior relapsers: subjects who had undetectable HCV RNA at the end of treatment in parent study but reverted to detectable levels of HCV RNA after stopping treatment in parent study were categorized as prior relapsers. Percentage of prior relapsers with undetectable HCV RNA 24 weeks after the completion of treatment in this study were presented. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). (NCT00535847)
Timeframe: 24 weeks after the completion of treatment (up to Week 72)
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week | 96.0 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 48 Week | 100.0 |
| Other | 100.0 |
Cross Tabulation of Extended Rapid Viral Response (eRVR) and Sustained Viral Response (SVR) in With Prior Response
Cross tabulation of number of subjects with eRVR/SVR status in present study was presented with respect to prior response status of subjects in parent studies. eRVR=undetectable HCV RNA at Week 4 and Week 12, SVR=undetectable HCV RNA at end of treatment (EOT) and at 24 weeks after last dose of study treatment without any confirmed detectable HCV RNA in between. Prior response=subjects were categorized into following categories based on their viral response in the parent study: Null Response (less than [<] 1-log10 decrease in HCV RNA at Week 4 or <2-log10 decrease in HCV RNA at Week 12), Partial Response (greater than [>] 2-log10 decrease in HCV RNA at Week 12, but detectable HCV RNA at Week 24), Viral Breakthrough (detectable HCV RNA during treatment after achieving undetectable HCV RNA), Relapse (undetectable HCV RNA at EOT but detectable HCV RNA during viral follow-up). Plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay; lower limit of detection=10 IU/mL. (NCT00535847)
Timeframe: Baseline up to Week 72
| Intervention | participants (Number) |
|---|
| Prior Null Response | Prior Partial Response | Prior Viral Breakthrough | Prior Relapse |
|---|
| Achieved eRVR/Achieved SVR | 12 | 15 | 6 | 24 |
,| Achieved eRVR/Did Not Achieve SVR | 5 | 7 | 0 | 0 |
,| Did Not Achieve eRVR/Achieved SVR | 7 | 1 | 0 | 4 |
,| Did Not Achieve eRVR/Did Not Achieve SVR | 27 | 6 | 2 | 1 |
Number of Participants With Biochemical Response
Biochemical response was defined as alanine aminotransferase (ALT) normalization. (NCT00536263)
Timeframe: End of treatment (EOT) and 24 weeks after EOT
| Intervention | Participants (Number) |
|---|
| EOT | 24 weeks after EOT |
|---|
| PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks | 75 | 63 |
,| PEG 1.5 mcg/kg QW * 24 Weeks | 86 | 80 |
,| PEG 1.5 mcg/kg QW * 48 Weeks | 103 | 103 |
Number of Participants With Combined Response
Combined response was defined as HBV DNA <20,000 IU/mL and HBe seroconversion and alanine aminotransferase (ALT) normalization (NCT00536263)
Timeframe: End of treatment (EOT) and 24 weeks after EOT
| Intervention | Participants (Number) |
|---|
| EOT | 24 weeks after EOT |
|---|
| PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks | 11 | 18 |
,| PEG 1.5 mcg/kg QW * 24 Weeks | 11 | 23 |
,| PEG 1.5 mcg/kg QW * 48 Weeks | 23 | 45 |
Number of Participants With HBV-DNA < 200 IU/mL
HBV-DNA was tested by assay of Roche Cobas Taqman (the test lowest limit is 6 IU/mL) (NCT00536263)
Timeframe: End of treatment (EOT) and 24 weeks after EOT
| Intervention | Participants (Number) |
|---|
| EOT | 24 weeks after EOT |
|---|
| PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks | 10 | 12 |
,| PEG 1.5 mcg/kg QW * 24 Weeks | 14 | 12 |
,| PEG 1.5 mcg/kg QW * 48 Weeks | 21 | 22 |
Number of Participants With HBV-DNA Undetectable
Undetectable HBV-DNA was defined as having a level <6 IU/mL by polymerase chain reaction (PCR). (NCT00536263)
Timeframe: End of treatment (EOT) and 24 weeks after EOT
| Intervention | Participants (Number) |
|---|
| EOT | 24 weeks after EOT |
|---|
| PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks | 4 | 4 |
,| PEG 1.5 mcg/kg QW * 24 Weeks | 3 | 3 |
,| PEG 1.5 mcg/kg QW * 48 Weeks | 8 | 8 |
Number of Participants With HBeAg Loss
HBeAg Loss was tested by assay of Abbott MEIA (NCT00536263)
Timeframe: Up to Treatment Week 48
| Intervention | Participants (Number) |
|---|
| PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks | 31 |
| PEG 1.5 mcg/kg QW * 24 Weeks | 28 |
| PEG 1.5 mcg/kg QW * 48 Weeks | 43 |
Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss
HBeAg Loss was tested by Abbott Microparticle Enzyme Immunoassay (MEIA) (NCT00536263)
Timeframe: 24 weeks after end of treatment (EOT)
| Intervention | Participants (Number) |
|---|
| PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks | 39 |
| PEG 1.5 mcg/kg QW * 24 Weeks | 40 |
| PEG 1.5 mcg/kg QW * 48 Weeks | 70 |
Change From Baseline in Liver Biopsy Score
"Method for biopsy scoring was Knodell Scoring System (Histology Activity Index-HAI Score System):~Score I (periportal +/- bridging necrosis): 0 (none) to 10 (multilobular necrosis).~Score II (Intralobular degeneration and focal necrosis): 0 (none) to 4 (Marked [involvement of >2/3 of lobules or nodules]).~Score III (portal inflammation): 0 (none) to 4 (Marked [dense packing of~inflammatory cells in >2/3 of portal tracts]).~Score IV (fibrosis): 0 (none) to 4 (cirrhosis)." (NCT00536263)
Timeframe: Baseline to 24 weeks after end of treatment
| Intervention | Units on a scale (Mean) |
|---|
| Baseline | Change from Baseline |
|---|
| PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks | 8.0 | -1.1 |
,| PEG 1.5 mcg/kg QW * 24 Weeks | 8.4 | -1.7 |
,| PEG 1.5 mcg/kg QW * 48 Weeks | 8.2 | -1.6 |
HBe Seroconversion
HBe seroconversion was defined as HBeAg Loss and Anti-HBeAg Positive. These were tested by assay of Abbott MEIA. (NCT00536263)
Timeframe: End of treatment (EOT) and 24 weeks after EOT
| Intervention | Participants (Number) |
|---|
| EOT | 24 weeks after EOT |
|---|
| PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks | 31 | 38 |
,| PEG 1.5 mcg/kg QW * 24 Weeks | 27 | 36 |
,| PEG 1.5 mcg/kg QW * 48 Weeks | 40 | 67 |
Hepatitis B Surface Antigen (HBs) Seroconversion
HBs seroconversion was defined as having HBsAg Loss and Anti-HBs Positive (NCT00536263)
Timeframe: End of treatment (EOT) and 24 weeks after EOT
| Intervention | Participants (Number) |
|---|
| EOT | 24 weeks after EOT |
|---|
| PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks | 0 | 0 |
,| PEG 1.5 mcg/kg QW * 24 Weeks | 0 | 0 |
,| PEG 1.5 mcg/kg QW * 48 Weeks | 1 | 2 |
Hepatitis B Surface Antigen (HBsAg) Loss
HBsAg Loss was tested by assay of Abbott MEIA (NCT00536263)
Timeframe: End of treatment (EOT) and 24 weeks after EOT
| Intervention | Participants (Number) |
|---|
| EOT | 24 weeks after EOT |
|---|
| PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks | 1 | 1 |
,| PEG 1.5 mcg/kg QW * 24 Weeks | 1 | 1 |
,| PEG 1.5 mcg/kg QW * 48 Weeks | 4 | 4 |
Number of Participants With Hepatitis B Virus - Deoxyriboncleic Acid (HBV-DNA) <20,000 IU/mL
"HBV-DNA was tested by assay of Roche Cobas Taqman (the test~lowest limit is 6 IU/mL)" (NCT00536263)
Timeframe: End of treatment (EOT) and 24 weeks after EOT
| Intervention | Participants (Number) |
|---|
| EOT | 24 weeks after EOT |
|---|
| PEG 1.0 mcg/kg Weekly (QW) * 24 Weeks | 46 | 44 |
,| PEG 1.5 mcg/kg QW * 24 Weeks | 61 | 47 |
,| PEG 1.5 mcg/kg QW * 48 Weeks | 76 | 75 |
Volume of Central Compartment (Vc) of Pegylated Interferon ɑ-2B
"Pharmacokinetic (PK) analysis of pegylated ɑ-2b included only Stratum A patients who had PK studies performed.~Samples were analyzed for pegylated interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM." (NCT00539591)
Timeframe: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28
| Intervention | ml/kg (Median) |
|---|
| Peginterferon ɑ-2b/Non-Pegylated Interferon ɑ-2b | 772 |
Mean Total PedsQL 4.0 Scores for Child Quality of Life (QoL) Assessments (Stratum B)
QoL assessments were completed using Pediatrics Quality of Life Inventory (PedsQL v4.0). Scale range is 0-100 with higher scores reflecting better quality of life. PedsQL 4.0 healthy sample normative mean ± SD for child report = 83.0 ± 14.8. (NCT00539591)
Timeframe: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
| Intervention | units on a scale (Number) |
|---|
| Pretherapy | 90.3 |
| Week 2 | 93.1 |
| Week 4 | 72.8 |
| Week 8 | 79.2 |
| Week 12 | 68.1 |
| End of Therapy | 65.6 |
Mean Total PedsQL 4.0 Scores for Parent Quality of Life Assessments (Stratum A)
QoL assessments were completed using Pediatrics Quality of Live Inventory (PedsQL v4.0). Scale range is 0-100 with higher scores reflecting better quality of life. PedsQL 4.0 healthy sample normative mean ± SD for parent report = 87.6 ± 12.3. (NCT00539591)
Timeframe: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
| Intervention | units on a scale (Mean) |
|---|
| Pretherapy | 70.3 |
| Week 2 | 71.8 |
| Week 4 | 74.4 |
| Week 8 | 79.1 |
| Week 12 | 79.0 |
| Week 24 | 82.2 |
| End of Therapy | 87.5 |
| 6 Months After End of Therapy | 86.0 |
| 12 Months After End of Therapy | 87.3 |
Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Strata B1 and B2
"The objective was to assess the safety of temozolomide administered in combination with peginterferon a-2b in Stratum B participants.~Accrual was suspended any time during therapy if 2 or more of 6, 4 or more of 12, 6 or more of 18, 8 or more of 24, 10 or more of 30 participants experienced target toxicity defined as:~Grade 4 non-hematologic (non-hem) toxicity that does not resolve to ≤grade 1 within 2 weeks from the time next dose is due and is determined to be probably or definitely related to protocol therapy~Grade 4 non-hem toxicity that is NOT constitutional symptoms (fever, chills, fatigue and/or pain)~Grade 3 elevations in creatinine or BUN that are determined to be probably or definitely related to protocol therapy~Grade 4 cardiopulmonary toxicity that is determined to be probably or definitely related to protocol therapy~Grade 4 mood alteration (suicidal ideation; danger to self or others)" (NCT00539591)
Timeframe: 52 weeks
| Intervention | participants (Number) |
|---|
| Temozolomide/Peginterferon ɑ-2b With Measureable Disease | 0 |
| Temozolomide/Peginterferon ɑ-2b Without Measureable Disease | 0 |
Probability of Event-free Survival (EFS) of Stratum A Participants
The probability of EFS was estimated as time to first event (relapse, death or second malignancy). As of April 2016, 21 out of 23 participants had no events. The EFS rate was estimated by Kaplan-Meier method. (NCT00539591)
Timeframe: 3 years from diagnosis
| Intervention | probability (Number) |
|---|
| Peginterferon ɑ-2b/Non-pegylated Interferon ɑ-2b | 0.913 |
Mean Total PedsQL 3.0 Scores for Parent Cancer Quality of Life (QoL) Assessments (Stratum A)
QoL assessments were completed using Pediatrics Cancer Quality of Life Inventory (PedsQL v3.0). Scale range is 0-100 with higher scores reflecting better quality of life. (NCT00539591)
Timeframe: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
| Intervention | units on a scale (Mean) |
|---|
| Week 2 | 73.2 |
| Week 4 | 75.1 |
| Week 8 | 81.4 |
| Week 12 | 78.7 |
| Week 24 | 81.6 |
| End of Therapy | 85.6 |
| 6 Months After End of Therapy | 85.0 |
| 12 Months After End of Therapy | 89.1 |
Systemic Clearance (CL) of Interferon ɑ-2B
Samples were analyzed for interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM. (NCT00539591)
Timeframe: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion
| Intervention | l/hr/m^2 (Median) |
|---|
| Interferon ɑ-2b | 15.3 |
Apparent Clearance (CL) of Pegylated Interferon ɑ-2B
"Pharmacokinetic (PK) analysis of pegylated ɑ-2b included only Stratum A patients who had PK studies performed.~Samples were analyzed for pegylated interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM." (NCT00539591)
Timeframe: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28
| Intervention | ml/hr/kg (Median) |
|---|
| Peginterferon ɑ-2b/Non-Pegylated Interferon ɑ-2b | 19.8 |
Area Under the Curve (AUC) of Interferon ɑ-2b
Samples were analyzed for interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM. AUC is given as Time 0 to infinity. (NCT00539591)
Timeframe: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion
| Intervention | pcg * hr/ml (Median) |
|---|
| Peginterferon ɑ-2b/Non-Pegylated Interferon ɑ-2b | 5026 |
Area Under the Curve (AUC) of Pegylated Interferon ɑ-2B
"Pharmacokinetic (PK) analysis of pegylated ɑ-2b included only Stratum A patients who had PK studies performed.~Samples were analyzed for pegylated interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM. AUC is given as Time 0 through infinity." (NCT00539591)
Timeframe: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28
| Intervention | pcg * hr/ml (Median) |
|---|
| Week 5 - First Dose | 50556 |
| Week 28 - Steady State | 48480 |
ɑ Half Life of Pegylated Interferon ɑ-2B
"Pharmacokinetic (PK) analysis of pegylated ɑ-2b included only Stratum A patients who had PK studies performed.~Samples were analyzed for pegylated interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM." (NCT00539591)
Timeframe: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28
| Intervention | hours (Median) |
|---|
| Peginterferon ɑ-2b/Non-Pegylated Interferon ɑ-2b | 24.8 |
BASC-2 Psychological Assessment (Stratum A)
The Behavioral Assessment System for Children, 2nd Edition (BASC-2) was administered to parents, assessing for any effects on behavior or mood in children undergoing study therapy. The behavior system index (BSI) T-score (range 0-100) is reported for the BASC-2 assessment. Higher scores reflect greater behavioral problems. (NCT00539591)
Timeframe: Pretherapy, Week 4, Week 24, End of Therapy, and 6 Months Post End of Therapy
| Intervention | T score (Mean) |
|---|
| Pretherapy | 44.9 |
| Week 4 | 45.9 |
| Week 24 | 44.2 |
| End of Therapy | 47.2 |
| 6 Months After End of Therapy | 42.3 |
BRIEF Psychological Assessment (Stratum A)
The Behavioral Rating Inventory of Executive Function (BRIEF) was administered to parents, assessing for any effects on behavior or mood in children undergoing study therapy. The global executive composite (GEC) T-score (range 0-100) is reported for the BRIEF assessment. Higher scores reflect poorer executive function. (NCT00539591)
Timeframe: Pretherapy, Week 4, Week 24, End of Therapy, and 6 Months Post End of Therapy
| Intervention | T score (Mean) |
|---|
| Pretherapy | 47.9 |
| Week 4 | 50.8 |
| Week 24 | 48.6 |
| End of Therapy | 47.6 |
| 6 Months After End of Therapy | 42.6 |
Mean Total PedsQL 3.0 Scores for Child Cancer Quality of Life (QoL) Assessments (Stratum A)
QoL assessments were completed using Pediatrics Cancer Quality of Life Inventory (PedsQL v3.0). Scale range is 0-100 with higher scores reflecting better quality of life. (NCT00539591)
Timeframe: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
| Intervention | units on a scale (Mean) |
|---|
| Week 2 | 71.1 |
| Week 4 | 76.1 |
| Week 8 | 79.2 |
| Week 12 | 78.5 |
| Week 24 | 77.1 |
| End of Therapy | 77.0 |
| 6 Months After End of Therapy | 83.7 |
| 12 Months After End of Therapy | 85.4 |
Mean Total PedsQL 3.0 Scores for Child Cancer Quality of Life (QoL) Assessments (Stratum B)
QoL assessments were completed using Pediatrics Cancer Quality of Life Inventory (PedsQL v3.0). Scale range is 0-100 with higher scores reflecting better quality of life. (NCT00539591)
Timeframe: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
| Intervention | units on a scale (Number) |
|---|
| Week 2 | 92.8 |
| Week 4 | 90.1 |
| Week 8 | 93.2 |
| Week 12 | 79.6 |
| End of Therapy | 67.4 |
Volume of Central Compartment (Vc) of Interferon ɑ-2b
Samples were analyzed for interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM. (NCT00539591)
Timeframe: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion
| Intervention | l/m^2 (Median) |
|---|
| Interferon ɑ-2b | 25.1 |
Mean Total PedsQL 3.0 Scores for Parent Cancer Quality of Life (QoL) Assessments (Stratum B)
QoL assessments were completed using Pediatrics Cancer Quality of Life Inventory (PedsQL v3.0). Scale range is 0-100 with higher scores reflecting better quality of life. (NCT00539591)
Timeframe: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
| Intervention | units on a scale (Number) |
|---|
| Week 2 | 67.7 |
| Week 4 | 71.4 |
Mean Total PedsQL 4.0 Scores for Child Quality of Life (QoL) Assessments (Stratum A)
QoL assessments were completed using Pediatrics Quality of Life Inventory (PedsQL v4.0). Scale range is 0-100 with higher scores reflecting better quality of life. PedsQL 4.0 healthy sample normative mean ± SD for child report = 83.0 ± 14.8. (NCT00539591)
Timeframe: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
| Intervention | units on a scale (Mean) |
|---|
| Pretherapy | 75.5 |
| Week 2 | 71.6 |
| Week 4 | 77.2 |
| Week 8 | 79.3 |
| Week 12 | 77.8 |
| Week 24 | 80.6 |
| End of Therapy | 80.4 |
| 6 Months After End of Therapy | 87.5 |
| 12 Months After End of Therapy | 91.0 |
Mean Total PedsQL 4.0 Scores for Parent Quality of Life Assessments (Stratum B)
QoL assessments were completed using Pediatrics Quality of Live Inventory (PedsQL v4.0). Scale range is 0-100 with higher scores reflecting better quality of life. PedsQL 4.0 healthy sample normative mean ± SD for parent report = 87.6 ± 12.3. (NCT00539591)
Timeframe: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post
| Intervention | units on a scale (Number) |
|---|
| Pretherapy | 77.6 |
| Week 2 | 72.2 |
| Week 4 | 89.1 |
Half-Life of Interferon ɑ-2b
Samples were analyzed for interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM. (NCT00539591)
Timeframe: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion
| Intervention | hours (Median) |
|---|
| ɑ half-life | ß half-life |
|---|
| Peginterferon ɑ-2b/Non-Pegylated Interferon ɑ-2b | 0.7 | 14.7 |
Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Stratum A Patients
"The objective was to study the feasibility and safety of administering peginterferon a-2b weekly for 48 weeks following the initial induction phase to Stratum A participants.~Accrual was suspended during the 48-week course if 2 or more of 6, 4 or more of 12, 6 or more of 18, 8 or more of 24, 10 or more of 30 participants experienced target toxicity defined as:~Grade 4 non-hematologic (non-hem) toxicity that does not resolve to ≤grade 1 within 2 weeks from the time next dose is due and is determined to be probably or definitely related to protocol therapy~Grade 4 non-hem toxicity that is NOT constitutional symptoms (fever, chills, fatigue and/or pain)~Grade 3 elevations in creatinine or BUN that are determined to be probably or definitely related to protocol therapy~Grade 4 cardiopulmonary toxicity that is determined to be probably or definitely related to protocol therapy~Grade 4 mood alteration (suicidal ideation; danger to self or others)" (NCT00539591)
Timeframe: 52 weeks
| Intervention | participants (Number) |
|---|
| Grade 4 non-hem toxicity | Grade 4 non-hem/NOT constitutional | Grade 3 elevations in creatinine or BUN | Grade 4 cardiopulmonary toxicity | Grade 4 mood alteration |
|---|
| Peginterferon ɑ-2b/Non-pegylated Interferon ɑ-2b | 2 | 0 | 0 | 0 | 1 |
Tumor Response Rate
Tumor response rate of stratum B1 participants was evaluated after 1 treatment course of temozolomide plus peginterferon ɑ-2b. Complete response (CR) and partial response (PR) confirmed with repeated scan at least 4 weeks apart following completion of course 1 therapy. CR defined as disappearance of all target and non-target lesions with no new lesions detected. If available, no disease must be detected by immunocytology or serum tumor markers. PR defined as at least 30% decrease in disease measurement compared to disease measurement at study entry with no new lesions detected. Progressive disease (PD) defined as at least 20% increase in the disease measurement compared to the smallest disease measurement recorded since start of treatment, or appearance of one or more new lesions. Stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD compared to smallest disease measurement since start of treatment. (NCT00539591)
Timeframe: 8 weeks
| Intervention | participants (Number) |
|---|
| Progressive Disease | Clinical Remission |
|---|
| Stratum B1 | 2 | 0 |
Annualized Relapse Rate
Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated through negative binomial regression with robust variance estimation and covariate adjustment for geographic region using observed number of relapses as dependent variable, the log total amount of follow-up from date of first study treatment for each participant as an offset variable, and treatment group and geographic region as model covariates. (NCT00548405)
Timeframe: Up to 2 years
| Intervention | relapses per participant per year (Number) |
|---|
| Interferon Beta-1a | 0.52 |
| Alemtuzumab 12 mg | 0.26 |
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2
EDSS is an ordinal scale in half-point increments that qualifies disability in participants with multiple sclerosis (MS). It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS). Change was calculated by subtracting Baseline value from value at Year 2. (NCT00548405)
Timeframe: Baseline, Year 2
| Intervention | units on a scale (Mean) |
|---|
| Interferon Beta-1a | 0.21 |
| Alemtuzumab 12 mg | -0.20 |
Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2
Percent change in MS lesion volume as measured by MRI-T2 scan was calculated from MRI-T2-weighted scans as the following: (lesion volume at 2 years - lesion volume at Baseline)*100/ (lesion volume at Baseline). (NCT00548405)
Timeframe: Baseline, Year 2
| Intervention | percent change (Mean) |
|---|
| Interferon Beta-1a | 2.41 |
| Alemtuzumab 12 mg | -1.12 |
Percentage of Participants Who Were Relapse Free at Year 2
Participants were considered relapse free at Year 2 if they did not experience a relapse from the date of first study treatment to study completion at 24 months. Percentage of participants who were relapse free at Year 2, estimated using the KM method, was reported. (NCT00548405)
Timeframe: Year 2
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a | 46.70 |
| Alemtuzumab 12 mg | 65.38 |
Percentage of Participants With Sustained Accumulation of Disability (SAD)
EDSS is an ordinal scale in half-point increments that qualifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with a Baseline score of 1.0 or more; and the increase persisted for at least the next 2 scheduled assessments, that is, 6 consecutive months. The onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Percentage of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported. (NCT00548405)
Timeframe: Up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a | 21.13 |
| Alemtuzumab 12 mg | 12.71 |
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2
MSFC is a multidimensional measure consisting of quantitative tests of ambulation (Timed 25-Foot Walk), manual dexterity (9-Hole Peg Test; 9HPT), and cognitive function (Paced Auditory Serial Addition Test; PASAT). The MSFC score was calculated as the mean of the Z-scores of the 3 components. A Z-score was calculated by subtracting the mean of the reference population from the test result, then dividing by the standard deviation of the reference population. Higher Z-scores reflected better neurological function and a positive change from Baseline indicates improvement. An increase in score indicated an improvement (Z-score range: -3 to +3). Acquisition of disability was measured by change from Baseline in MSFC score at Year 2. (NCT00548405)
Timeframe: Baseline, Year 2
| Intervention | Z-score (Mean) |
|---|
| Baseline (n=198, 423) | Change at Year 2 (n=169, 399) |
|---|
| Alemtuzumab 12 mg | 0.02 | 0.09 |
,| Interferon Beta-1a | -0.03 | -0.04 |
Efficacy of GM-CSF and Pegylated Interferon-alpha 2b When Administered to Patients With AML, ALL, Blast Phase CML, and MDS Relapse After Allogeneic Transplantation, Defined as Progression-free Survival of > 33% at 3 Months
Efficacy is defined as progression-free survival of > 33% at 3 months. This is based on our retrospective data on 10% 3 month survival for relapsed patients. Progression is defined an an increase in blasts in blood or marrow by 50% compared to baseline with at least 20% of all cells being blasts at the time of assessment. (NCT00548847)
Timeframe: 3 months after cytokine treatment
| Intervention | percentage of progression-free patients (Number) |
|---|
| GM-CSF, Interferon-α-2b | 13 |
Central Review-based Progression-Free Survival
From date of randomization (which is the date of registration) to date of first documentation of progression based on Central Radiological Review of the appropriate CT or MRI scans, or symptomatic deterioration (as defined in Section 10.2e)), or development of new lesions or disease not identified on CT or MRI, or death due to any cause. Patients who have a local assessment of progression based on imaging, but for whom central review does not concur, will be censored at the last Central Radiological Review date, unless subsequent scans or documentation of symptomatic deterioration provides evidence of progression. Patients last known not to have progressed are censored at the date of last contact. Patients with incomplete Central Radiological Review are censored at the date of last Central Radiological Review if patient has not progressed prior to that time. (NCT00569127)
Timeframe: Up to 3 years
| Intervention | months (Median) |
|---|
| Octreotide, Bevacizumab | 16.6 |
| Octreotide, Interferon Alpha-2b | 15.4 |
Objective Response (Confirmed and Unconfirmed Complete Response and Partial Response)
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0): Complete Response (CR) is disappearance of all measurable and non-measurable disease, and no new lesions; Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions, no unequivocal progression of non-measurable disease, and no new lesions. Confirmed response is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR. (NCT00569127)
Timeframe: Up to 3 years
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Unconfirmed Complete Response | Unconfirmed Partial Response | Stable/No Resposne | Increasing Disease | Symptomatic Deterioration | Assessment Inadequate |
|---|
| Octreotide, Bevacizumab | 2 | 20 | 0 | 7 | 135 | 20 | 0 | 16 |
,| Octreotide, Interferon Alpha-2b | 0 | 8 | 1 | 6 | 137 | 30 | 3 | 17 |
Overall Survival
From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. (NCT00569127)
Timeframe: Up to 7 years
| Intervention | months (Median) |
|---|
| Octreotide, Bevacizumab | 35.2 |
| Octreotide, Interferon Alpha-2b | 47.3 |
Local Progression-Free Survival (Investigator Assessed)
From date of randomization (which is the date of registration) to date of first documentation of progression [per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as defined in Section 10.2d] or symptomatic deterioration (as defined in Section 10.2e), or death due to any cause. Patients last known not to have progressed are censored at date of last contact. Progression (Section 10.2d) includes one or more of the following: 20% increase in the sum of the longest diameters of target measurable lesions over smallest sum observed using the same techniques as baseline; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of new lesion/site; or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration (Section 10.2e) is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. (NCT00569127)
Timeframe: Up to 3 years
| Intervention | months (Median) |
|---|
| Octreotide, Bevacizumab | 15.4 |
| Octreotide, Interferon Alpha-2b | 10.6 |
Time to Treatment Failure
From date of randomization (which is the date of registration) to date of first observation of progressive disease (as defined in Section 10.2d), death due to any cause, symptomatic deterioration (as defined in Section 10.2e), or discontinuation of treatment. This has been calculated using Central-Review based progression events. Patients last known not to have failed treatment are censored at date last known not to have failed. Patients with incomplete Central Radiological Review are censored at the date of last Central Radiological Review if patient has not failed treatment prior to that time. (NCT00569127)
Timeframe: Up to 3 years
| Intervention | months (Median) |
|---|
| Octreotide, Bevacizumab | 9.9 |
| Octreotide, Interferon Alpha-2b | 5.6 |
Number of Participants With Overall Survival (10 Years) by Treatment
Overall Survival is the time from date of treatment start until date of death due to any cause or last Follow-up within 10 years. (NCT00577993)
Timeframe: 10 Years
| Intervention | Participants (Count of Participants) |
|---|
| Fludarabine,Mitoxantrone, and Dexamethasone (FND)-Rituximab | 59 |
| Rituximab- Fludarabine,Mitoxantrone, and Dexamethasone (FND) | 58 |
Number of Participants With Progression Free Survival (10 Years) by Treatment
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00577993)
Timeframe: 10 years
| Intervention | Participants (Count of Participants) |
|---|
| Fludarabine,Mitoxantrone, and Dexamethasone (FND)-Rituximab | 59 |
| Rituximab- Fludarabine,Mitoxantrone, and Dexamethasone (FND) | 58 |
Percentage of Participants With Sustained Viral Response (SVR)
Sustained viral response was defined as having undetectable HCV RNA at EOT (Week 48/50 or early discontinuation) and no confirmed detectable HCV RNA levels between EOT and 12 weeks (SVR12) and 24 weeks (SVR24) after the last dose of study medication. (NCT00580801)
Timeframe: Week 12 and 24 after the last dose of study medication
| Intervention | Percentage of participants (Number) |
|---|
| SVR12 | SVR24 |
|---|
| Placebo+Pegylated-interferon-alfa-2a+Ribavirin | 62.5 | 62.5 |
,| Telaprevir and Then Pegylated-interferon-alfa-2a+Ribavirin | 75.0 | 62.5 |
,| Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin | 50.0 | 50.0 |
Percentage of Participants With Viral Response (Undetectable HCV RNA)
Viral response was either defined as having undetectable HCV RNA (that is, no HCV RNA was detected in the participants' plasma samples) or less than 25 IU/mL HCV RNA from Day 15 up to end of treatment (EOT), that is Week 48/50 or early discontinuation. In Week x/y, where, x represents time frame for Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin and Placebo+Pegylated-interferon-alfa-2a+Ribavirin and; y represents time frame for Telaprevir and Pegylated-interferon-alfa-2a+Ribavirin treatment group. (NCT00580801)
Timeframe: Day 15 up to EOT (Week 48/50 or early discontinuation)
| Intervention | Percentage of participants (Number) |
|---|
| Day 15 (n=7, 8, 8) | Week 4/6 (n=7, 8, 8) | Week 12/14 (n=7, 8, 7) | Week 24/26 (n=6, 8, 8) | Week 36/38 (n=6, 8, 5) | Week 48/50 (n=4, 7, 5) | EOT (n=8, 8, 8) |
|---|
| Placebo+Pegylated-interferon-alfa-2a+Ribavirin | 0 | 12.5 | 57.1 | 62.5 | 100 | 100 | 75.0 |
,| Telaprevir and Then Pegylated-interferon-alfa-2a+Ribavirin | 0 | 42.9 | 85.7 | 100 | 100 | 100 | 87.5 |
,| Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin | 12.5 | 37.5 | 75.0 | 87.5 | 75.0 | 85.7 | 75.0 |
Time to Reach the Maximum Serum Concentration (Tmax) of Telaprevir
The tmax is the time to reach maximum observed serum concentration of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and pegylated-interferon-alfa-2a+Ribavirin (test). (NCT00580801)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
| Intervention | Hours (Median) |
|---|
| tmax: Day 1 (n=8, 8) | tmax: Day 15 (n=7, 7) |
|---|
| Telaprevir and Then Pegylated-interferon-alfa-2a+Ribavirin | 4.02 | 2.92 |
,| Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin | 4.00 | 3.00 |
Area Under the Serum Concentration-Time Curve (AUC)
The AUC is a measure of the serum concentration-time curve, calculated by the lin-up/log-down method. (NCT00580801)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
| Intervention | nanogram*hour/milliliter (ng*h/mL) (Mean) |
|---|
| AUC : Day 1 (n=8, 7) | AUC : Day 15 (n=7, 7) |
|---|
| Telaprevir and Then Pegylated-interferon-alfa-2a+Ribavirin | 6702 | 17120 |
,| Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin | 7467 | 23320 |
Number of Participants With Viral Breakthrough (Detectable HCV RNA)
Viral breakthrough was defined as having a confirmed increase greater than 1 log 10 in HCV RNA level from the lowest level reached, or a confirmed level of HCV RNA greater than 100 IU/mL in participants whose HCV RNA had previously become undetectable [less than 25 IU/mL]). In Week x/y, where, x represents time frame for Telaprevir+pegylated-interferon-alfa-2a+Ribavirin and Placebo+pegylated-interferon-alfa-2a+Ribavirin and y represents time frame for Telaprevir and then Pegylated-interferon-alfa-2a+Ribavirin treatment group. (NCT00580801)
Timeframe: Day 8, Day 12, Day 15, Week 24/26 and Week 36/38
| Intervention | Participants (Number) |
|---|
| Day 8 | Day 12 | Day 15 | Week 24/26 | Week 36/38 |
|---|
| Placebo+Pegylated-interferon-alfa-2a+Ribavirin | 0 | 0 | 0 | 1 | 1 |
,| Telaprevir and Then Pegylated-interferon-alfa-2a+Ribavirin | 1 | 3 | 5 | 5 | 5 |
,| Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin | 0 | 0 | 0 | 0 | 2 |
Average Steady-State Serum Concentration (Css,av) of Telaprevir
The Average steady-state serum concentration (Css,av) was calculated by AUC/τ at steady-state (τ=dosing interval) of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test). (NCT00580801)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
| Intervention | Nanogram/milliliter (ng/mL) (Mean) |
|---|
| Telaprevir and Then Pegylated-interferon-alfa-2a+Ribavirin | 2141 |
| Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin | 2896 |
Minimum Serum Concentration (Cmin) of Telaprevir on Day 15
The Cmin is the minimum serum concentration between 0 hour and τ (τ=dosing interval) of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test). Cmin on Day 15 is reported here. (NCT00580801)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 15
| Intervention | Nanogram/milliliter (ng/mL) (Mean) |
|---|
| Telaprevir and Then Pegylated-interferon-alfa-2a+Ribavirin | 1639 |
| Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin | 2100 |
Percentage of Participants With Relapse
Relapse was defined as having confirmed detectable HCV RNA during the 24-week follow-up period in participants who had undetectable HCV RNA at EOT (Week 48/50 or early discontinuation). Participants who dropped out between 24-week follow-up after EOT were not evaluated for relapse. (NCT00580801)
Timeframe: Week 24 after EOT (Week 48/50 or early discontinuation)
| Intervention | Percentage of participants (Number) |
|---|
| Telaprevir and Then Pegylated-interferon-alfa-2a+Ribavirin | 14.3 |
| Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin | 33.3 |
| Placebo+Pegylated-interferon-alfa-2a+Ribavirin | 16.7 |
Pre-Dose Serum Concentration (C[0h]) of Telaprevir
The C(0h) is the pre-dose serum concentration of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test). (NCT00580801)
Timeframe: 0 hour (pre-dose) at Day 15
| Intervention | Nanogram/milliliter (ng/mL) (Mean) |
|---|
| Telaprevir and Then Pegylated-interferon-alfa-2a+Ribavirin | 1873 |
| Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin | 2806 |
Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Day 15
The plasma HCV RNA levels were used to assess the antiviral activity which included viral response as either undetectable HCV RNA (that is no HCV target was detected in the plasma sample) or less than 25 International unit per milliliter (IU/mL) of HCV RNA (that is Plasma sample contained HCV RNA at a concentration below the limit of quantification [LLOQ=25 IU/mL] of the viral load assay). Plasma HCV RNA levels were measured using the COBAS TaqMan HCV test Version 2.0. This assay used real-time reverse transcription-polymerase chain reaction (RT-PCR) methodology. (NCT00580801)
Timeframe: Baseline and Day 15
| Intervention | log 10 IU/mL (Median) |
|---|
| HCV RNA levels: Baseline (n=8,8,8) | HCV RNA levels: Change at Day 15 (n=7,8,8) |
|---|
| Placebo+Pegylated-interferon-alfa-2a+Ribavirin | 5.88 | -1.58 |
,| Telaprevir and Then Pegylated-interferon-alfa-2a+Ribavirin | 5.83 | -0.77 |
,| Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin | 6.16 | -4.32 |
Maximum Serum Concentration (Cmax) of Telaprevir
The Cmax is the maximum observed serum concentration, which was measured at Day 1 and 15 for telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test). (NCT00580801)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
| Intervention | Nanogram/milliliter (ng/mL) (Mean) |
|---|
| Cmax: Day 1 (n=8, 8) | Cmax: Day 15 (n=7, 7) |
|---|
| Telaprevir and Then Pegylated-interferon-alfa-2a+Ribavirin | 1598 | 2733 |
,| Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin | 1709 | 3669 |
HIV Viral Load < 400 Copies/ml
% of individuals maintaining viral suppression (VL < 400 copies/ml) as compared to the anticipated rate of viral suppression in individuals interrupting ART without interferon (9%) (NCT00594880)
Timeframe: 12 weeks
| Intervention | percentage of participants (Number) |
|---|
| Pegasys 180 mcg/Week | 40 |
| Pegasys 90 mcg/Week | 50 |
HIV Viral Load < 48 Copies/ml
% of individuals maintaining VL < 48 copies/ml while on pegylated interferon alpha-2a treatment without ART (NCT00594880)
Timeframe: 12 weeks
| Intervention | percentage of participants (Number) |
|---|
| 180 mcg/Week | 10 |
| 90 mcg/Week | 30 |
HIV Viral Load < 400 Copies/ml
% of individuals maintaining viral suppression (VL < 400 copies/ml) as compared to the anticipated rate of viral suppression in individuals interrupting ART without interferon (9%) (NCT00594880)
Timeframe: 24 weeks
| Intervention | percentage of eligible participants (Number) |
|---|
| 180 mcg/Week | 67 |
| 90 mcg/Week | 80 |
Percent Change From Baseline in Brain Volume
Change in brain volume was derived from MRI scans obtained at baseline and at Month 24. (NCT00605215)
Timeframe: Baseline, Month 24
| Intervention | Percent Change (Mean) |
|---|
| Placebo | -0.53 |
| Laquinimod | -0.51 |
| Avonex® | -0.53 |
Accumulation of Physical Disability Measured by the Number of Participants With Confirmed Progression of EDSS
A confirmed progression of EDSS was defined as a 1 point increase from baseline on EDSS score if baseline EDSS was between 0 and 5.0, or a 0.5 point increase if baseline EDSS was 5.5, confirmed 3 months later. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]). Data is presented as distribution of confirmed progression (number of participants with confirmed progression of EDSS) sustained for 3 months. Progression could not be confirmed during a relapse. (NCT00605215)
Timeframe: Baseline up to Month 24
| Intervention | Participants (Count of Participants) |
|---|
| Placebo | 60 |
| Laquinimod | 42 |
| Avonex® | 47 |
Change From Baseline in Disability as Assessed by the Multiple Sclerosis Functional Composite (MSFC) Score
The Multiple Sclerosis Functional Composite is an instrument assessing disability that consists of 3 clinical assessments. The 3 are Timed 25-Foot Walk, 9-Hole Peg Test which measures upper extremity (arm and hand) function, and PASAT (Paced Auditory Serial Addition Test) which is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. A Z-score is used to define a common metric from the 3 assessments that constitute the MSFC score. The study's population at baseline was used as reference population for the Z-score calculation. A Z-score of 0 represents the population mean at baseline. Higher Z-scores correspond to an improved outcome. (NCT00605215)
Timeframe: Baseline, Month 24
| Intervention | Z score (Mean) |
|---|
| Placebo | -0.5 |
| Laquinimod | -0.00 |
| Avonex® | -0.01 |
Annualized Rate of Confirmed Relapses
A relapse was defined as the appearance of new neurological abnormalities or the reappearance of previously observed neurological abnormalities; lasting at least 48 hours and immediately preceded by an improved neurological state of ≥30 days from onset of previous relapse, accompanied by observed objective neurological changes (an increase of ≥0.5 in Expanded Disability Status Scale [EDSS] score, or an increase of 1 grade in the score of 2 or more of the 7 Functional Systems [FS], or an increase of 2 grades in the score of 1 FS as compared to the previous evaluation). Total number of confirmed relapses during the treatment period was divided by the sum of number of days on study in the treatment period and then multiplied by the number of days in the year to calculate the annualized relapse rate. Annualized relapse rate was derived from a baseline-adjusted negative binomial regression. (NCT00605215)
Timeframe: Baseline up to Month 24
| Intervention | relapse per year (Mean) |
|---|
| Placebo | 0.344 |
| Laquinimod | 0.283 |
| Avonex® | 0.255 |
Cumulative Number of Enhancing Lesions on T1-Weighted Images
The cumulative number of T1 Gadolinium (Gd)-enhancing lesions was calculated as the sum of the numbers of Gd-enhancing lesions observed on scans taken at Months 12 and 24. (NCT00605215)
Timeframe: Months 12 and 24
| Intervention | lesions (Mean) |
|---|
| Placebo | 2.70 |
| Laquinimod | 2.58 |
| Avonex® | 1.23 |
Cumulative Number of New or Enlarging Hypointense Lesions on Enhanced T1 Scans
The cumulative number of new or enlarging hypointense lesions was calculated as the sum of the numbers of new or enlarging hypointense lesions observed on scans taken at Months 12 and 24. (NCT00605215)
Timeframe: Months 12 and 24
| Intervention | lesions (Mean) |
|---|
| Placebo | 7.10 |
| Laquinimod | 7.33 |
| Avonex® | 5.91 |
EVR (Early Virologic Response)
Early Virologic Response (EVR) is a response measured by the reduction of virus in the blood after 12 weeks of treatment. (NCT00606086)
Timeframe: At 12 weeks of treatment
| Intervention | percentage of participants (Number) |
|---|
| Arm 1: Peg-IFN/Ribavirin Plus GI-5005 | 79.4 |
| Arm 2: Peg-IFN/Ribavirin or Peg-IFN/Ribavirin Plus GI-5005 | 78.5 |
Summary of Disease Progression in Study Participants, Intent-to-treat Population
Number of evaluable study participants who had died or experienced objective disease progression (no clinical objective response to treatment as evaluated by computed tomography [CT] scans or physical examination). (NCT00613509)
Timeframe: Day 0 up to 35 weeks post 1st vaccination or treatment
| Intervention | Participants (Number) |
|---|
| Progressed or died due to any cause | Did not progress or die due to any cause |
|---|
| Study Group 1: ALVAC Melanoma Vaccine | 7 | 4 |
,| Study Group 2: Interferon Alpha-2b | 6 | 6 |
Summary of Cellular Immune Response to the Vaccination or Treatment (Percent Regulatory T-Cells Responses)
The immunogenicity of the treatment regimens was assessed by regulatory T-cell responses as assessed primarily by the multi-parametric intracellular cytokine staining (ICS) assay. (NCT00613509)
Timeframe: Day 0 to 32 weeks post 1st vaccination or treatment
| Intervention | Percent Cell Count (Mean) |
|---|
| Screening | Cycle 1 Week 1 | Cycle 1 Week 7 | Cycle 2 Week 23 | Cycle 2 Week 32 |
|---|
| Study Group 1: ALVAC Melanoma Vaccine | 2.7 | 3.3 | 2.9 | 3.3 | 4.0 |
,| Study Group 2: Interferon Alpha-2b | 3.4 | 2.3 | 3.1 | 3.8 | 2.6 |
Number of Participants With a Vaccine-Induced Increase of CD8 T-Cell Positive Response by Antigen
The vaccine-induced increase of CD8 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values. (NCT00613509)
Timeframe: Day 0 to 32 weeks post 1st vaccination
| Intervention | Participants (Number) |
|---|
| Screening: gp100 pool1 | Screening: gp100 pool2 | Screening: gp100 pool3 | Screening: gp100 pool4 | Screening: gp100 pool5 | Screening: gp100 pool6 | Screening: NYESO-1 pool 1 | Screening: NYESO-1 pool 2 | Screening: Mart1 pool | Screening: Native 15mer pool | Screening: 9mer pool | 7 Weeks post 1st Vaccination: gp100 pool1 | 7 Weeks post 1st Vaccination: gp100 pool2 | 7 Weeks post 1st Vaccination: gp100 pool3 | 7 Weeks post 1st Vaccination: gp100 pool4 | 7 Weeks post 1st Vaccination: gp100 pool5 | 7 Weeks post 1st Vaccination: gp100 pool6 | 7 Weeks post 1st Vaccination: NYESO-1 pool 1 | 7 Weeks post 1st Vaccination: NYESO-1 pool 2 | 7 Weeks post 1st Vaccination: Mart1 pool | 7 Weeks post 1st Vaccination: Native 15mer pool | 7 Weeks post 1st Vaccination: 9mer pool |
|---|
| Study Group 1: ALVAC Melanoma Vaccine | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Study Group 2: Interferon Alpha-2b | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With a Vaccine-Induced Increase of CD4 T-Cell Positive Response by Antigen
The Vaccine-induced increase of CD4 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values. (NCT00613509)
Timeframe: Day 0 to 32 weeks post 1st vaccination
| Intervention | Participants (Number) |
|---|
| Screening: gp100 pool1 | Screening: gp100 pool2 | Screening: gp100 pool3 | Screening: gp100 pool4 | Screening: gp100 pool5 | Screening: gp100 pool6 | Screening: NYESO-1 pool 1 | Screening: NYESO-1 pool 2 | Screening: Mart1 pool | Screening: Native 15mer pool | Screening: 9mer pool | 7 Weeks post 1st Vaccination: gp100 pool1 | 7 Weeks post 1st Vaccination: gp100 pool2 | 7 Weeks post 1st Vaccination: gp100 pool3 | 7 Weeks post 1st Vaccination: gp100 pool4 | 7 Weeks post 1st Vaccination: gp100 pool5 | 7 Weeks post 1st Vaccination: gp100 pool6 | 7 Weeks post 1st Vaccination: NYESO-1 pool 1 | 7 Weeks post 1st Vaccination: NYESO-1 pool 2 | 7 Weeks post 1st Vaccination: Mart1 pool | 7 Weeks post 1st Vaccination: Native 15mer pool | 7 Weeks post 1st Vaccination: 9mer pool |
|---|
| Study Group 1: ALVAC Melanoma Vaccine | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Study Group 2: Interferon Alpha-2b | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants Reporting a Grade 3 or Grade 4 Adverse Events by Preferred Term
"Common Terminology Criteria for Adverse Events (CTCAE) definitions:~Grade 3 is a severe adverse event; Grade 4 is a life-threatening or disabling adverse event." (NCT00613509)
Timeframe: Day 0 to 12 months post last vaccination
| Intervention | Participants (Number) |
|---|
| Anemia | Leukocytosis | Abdominal Pain Upper | Axillary Pain | Chest Discomfort | Chest Pain | Inflammation | Pyrexia | Sepsis | Septic Shock | Staphylococcal Bacteremia | Alanine Aminotransferase (ALT) Increased | Aspartate Aminotransferase (AST) Increased | Gamma-Glutamyl Transferase (GGT) Increased | Neutrophil Count Decreased | White Blood Cell Count Decreased | Hypernatremia | Hypoalbuminemia | Hypocalcemia | Hyponatremia | Joint Range of Motion Decreased | Metastatic Malignant Melanoma | Brain Edema | Cerebral Hemorrhage | Encephalopathy | Headache | Hemiplegia | Paraesthesia | Peripheral Sensory Neuropathy | Syncope Vasovagal | Polyuria | Hypotension |
|---|
| Study Group 1: ALVAC Melanoma Vaccine | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 1 |
,| Study Group 2: Interferon Alpha-2b | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 3 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 |
Best Overall Objective Response as Number of Participants Responding in the Intent-to-treat Population
Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. (NCT00613509)
Timeframe: Day 0 to 32 weeks post 1st vaccination or treatment
| Intervention | Particpants (Number) |
|---|
| Participants with measurable disease at baseline | Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Not Evaluable (NE) | Progression (PD) |
|---|
| Study Group 1: ALVAC Melanoma Vaccine | 11 | 0 | 2 | 3 | 0 | 6 |
,| Study Group 2: Interferon Alpha-2b | 11 | 0 | 1 | 3 | 1 | 6 |
Progression-Free Survival Time by Response Evaluation Criteria in Solid Tumor (RECIST) Criteria in the Intent-to-treat Population
Progression-Free Survival was assessed by the Response Evaluation Criteria in Solid Tumor criteria from the computed tomography (CT) scans, as per-protocol (NCT00613509)
Timeframe: Day 0 - up to 35 weeks post 1st vaccination or treatment
| Intervention | Weeks (Median) |
|---|
| Study Group 1: ALVAC Melanoma Vaccine | 15.9 |
| Study Group 2: Interferon Alpha-2b | 8.9 |
Best Overall Objective Response as Mean Duration of Response (Weeks) in the Intent-to-treat Population
Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. (NCT00613509)
Timeframe: Day 0 to 32 weeks post 1st vaccination or treatment
| Intervention | Weeks (Mean) |
|---|
| Study Group 1: ALVAC Melanoma Vaccine | 16.3 |
| Study Group 2: Interferon Alpha-2b | 18.3 |
Best Overall Objective Response in the Intent-to-treat Population
Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. (NCT00613509)
Timeframe: Day 0 to 32 weeks post 1st vaccination or treatment
| Intervention | Percentage of participants (Number) |
|---|
| Study Group 1: ALVAC Melanoma Vaccine | 18.2 |
| Study Group 2: Interferon Alpha-2b | 9.1 |
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE, can therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. All AE's were analyzed based on the principle of treatment emergence. An AE was regarded as treatment-emergent if it was not present prior to receiving the first injection but subsequently appeared, or if it was present prior to receiving the first injection and subsequently worsened in severity. (NCT00616434)
Timeframe: Up to 16 weeks
| Intervention | participants (Number) |
|---|
| Interferon Beta-1a | 52 |
| Placebo | 35 |
Percentage of Participants With a Clinical Response
Clinical response is defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, accompanied by a decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore of 1 or less. Baseline was defined as the score collected during the screening period. The Mayo Score/Disease Activity Index (DAI) measures disease activity through assessment of 4 items: stool frequency, rectal bleeding, endoscopy findings, and Physician Global Assessment (PGA). Each item of the score is assessed on a 4-point scale, 0, 1, 2, or 3, with a higher score representing greater severity. In this study, the endoscopy subscore was expanded to a 5-point scale to increase sensitivity in this important dimension of the disease (0=normal/inactive disease, 4=deep ulceration). The Total Mayo Score can therefore range from 0 to13 points. (NCT00616434)
Timeframe: Baseline and Week 8
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a | 53 |
| Placebo | 44 |
Percentage of Participants With a Decrease on Simple Clinical Colitis Activity Index (SCCAI) of ≥3 Points at Week 8
The SCCAI measures disease activity as defined by both participants and examiners and includes the following 13 items: general well-being, abdominal pain, bowel frequency, stool consistency, bleeding, anorexia, nausea or vomiting, abdominal tenderness, extra-intestinal complications (eye, mouth, joint, skin), temperature, sigmoidoscopic assessment, nocturnal bowel movements, and urgency of defecation. Scores range from 0 to 19 points, and scores <2.5 have been shown to correlate with Patient-Defined Remission, and a decrease of >1.5 points from Baseline correlates with Patient-Defined Significant Improvement. Baseline is defined as the mean of the screening and visit 1 scores. (NCT00616434)
Timeframe: Baseline and Week 8
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a | 64 |
| Placebo | 46 |
Number of Subjects With Undetectable HCV RNA at Week 72
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. (NCT00627926)
Timeframe: Week 72 (24 weeks after last dose for subjects with a planned treatment duration of 48 weeks and 48 weeks after last dose for subjects with planned treatment duration of 24 weeks)
| Intervention | participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 158 |
| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 243 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 265 |
Number of Subjects Achieving Extended Rapid Viral Response (eRVR), Demonstrated by Achieving Undetectable HCV RNA at Week 4 and at Week 12
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. eRVR was defined as undetectable HCV RNA at both Week 4 and Week 12. (NCT00627926)
Timeframe: Week 4 and Week 12
| Intervention | participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 29 |
| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 207 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 212 |
Number of Subjects Achieving Rapid Viral Response (RVR), Demonstrated by Achieving Undetectable HCV RNA 4 Weeks After Starting Study Treatment
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. RVR was defined as undetectable HCV RNA 4 weeks after the start of study treatment. (NCT00627926)
Timeframe: Week 4
| Intervention | participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 34 |
| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 242 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 246 |
Number of Subjects With Undetectable HCV RNA 12 Weeks After Last Planned Dose of Study Treatment
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. (NCT00627926)
Timeframe: 12 weeks after last planned dose of study treatment (up to Week 60)
| Intervention | participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 161 |
| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 255 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 275 |
Number of Subjects With Undetectable HCV RNA 24 Weeks After Last Actual Dose of Study Treatment
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. (NCT00627926)
Timeframe: 24 weeks after last actual dose of study treatment (up to Week 72)
| Intervention | participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 158 |
| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 251 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 274 |
Number of Subjects With Undetectable HCV RNA at End of Treatment (EOT)
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. (NCT00627926)
Timeframe: End of treatment (up to Week 48)
| Intervention | participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 229 |
| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 295 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 314 |
Number of Subjects With Undetectable HCV RNA at Week 12
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. (NCT00627926)
Timeframe: Week 12
| Intervention | participants (Number) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 146 |
| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 277 |
| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 283 |
Biochemical Response: Number of Subjects With Grade 3 and 4 Shifts From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels
Criteria for grading severity (toxicity) of ALT and AST: Grade 0 (<1.25*upper limit of normal [ULN]); Grade 1 (mild=1.25 to 2.5*ULN); Grade 2 (moderate=2.6 to 5.0*ULN); Grade 3 (severe= greater than 5.0 to 20.0*ULN); Grade 4 (life-threatening= greater than 20.0*ULN). Number of subjects with Grade 3 shift (from Grade 0, Grade 1 or Grade 2 baseline) and Grade 4 shift (from Grade 0, Grade 1, Grade 2 or Grade 3 baseline) are reported. If a subject experienced more than 1 severity grade shifts during post baseline assessments, the maximum severity grade shift was considered. (NCT00627926)
Timeframe: Baseline up to Week 48
| Intervention | participants (Number) |
|---|
| ALT Grade 3 toxicity grade shift | ALT Grade 4 toxicity grade shift | AST Grade 3 toxicity grade shift | AST Grade 4 toxicity grade shift |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 12 | 0 | 19 | 1 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 6 | 0 | 10 | 0 |
,| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 5 | 1 | 7 | 0 |
Fatigue Severity Scale (FSS) Total Score
FSS was a 9-item questionnaire where each item was scored on a scale of 1 to 7 (higher scores indicated higher influence of fatigue). FSS total score was calculated as the average of individual items on the questionnaire and FSS total score ranged from 1 to 7, where higher score indicated higher influence of fatigue. (NCT00627926)
Timeframe: Baseline, Week 4, 12, 24, 36, 48, 72
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n=343, 351, 346) | Week 4 (n=334, 326, 329) | Week 12 (n=329, 310, 312) | Week 24 (n=317, 307, 304) | Week 36 (n=296, 282, 297) | Week 48 (n=286, 282, 294) | Week 72 (n=296, 270, 289) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 3.0 | 4.1 | 4.4 | 4.3 | 4.1 | 4.0 | 2.9 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 3.0 | 4.5 | 4.8 | 4.3 | 3.3 | 3.1 | 2.6 |
,| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 3.2 | 4.4 | 4.4 | 4.3 | 3.4 | 3.0 | 2.6 |
Noninvasive Markers of Fibrosis: Number of Subjects With Improvement in FibroTest Analysis
FibroTest analysis was a biomarker analysis test used to generate a score that was correlated with the degree of liver damage. The FibroTest score was calculated from the results of a six-parameter blood test, combining six serum markers (alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, gamma-glutamyl transpeptidase, total bilirubin, and alanine transaminase). The FibroTest score (F score) may range from 0.00 (Grade F0) to 1.00 (Grade F4), where F0= no fibrosis and F4=cirrhosis. Results were presented separately for subjects who achieved SVR at 24 weeks after the last planned dose of study treatment and those who did not achieve SVR at 24 weeks after the last planned dose of study treatment. Improvement was defined as decrease of at least 1 grade relative to baseline. (NCT00627926)
Timeframe: Baseline through 24 weeks after last planned dose of study treatment (up to Week 72)
| Intervention | participants (Number) |
|---|
| SVR achieved (136, 180, 214) | SVR not achieved (137, 53, 47) |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 35 | 31 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 84 | 12 |
,| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 59 | 12 |
Number of Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels 24 Weeks After Last Planned Dose of Study Treatment
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. Two results are reported: 1) Protocol defined SVR: undetectable HCV RNA at 24 weeks after the last planned dose of study treatment without any confirmed detectable HCV RNA between end of treatment visit (up to Week 48) and 24 weeks after last planned dose (up to Week 72); 2) SVR as per FDA guidance (snapshot analysis): undetectable HCV RNA at 24 weeks after the last planned dose of study treatment. Analysis was based only on the HCV RNA assessment in visit window (+/-2 weeks); if there were more than 1 assessment in the window, the last measurement was used. (NCT00627926)
Timeframe: 24 weeks after last planned dose of study treatment (up to Week 72)
| Intervention | participants (Number) |
|---|
| SVR: Protocol Defined | SVR: FDA Guidance |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 158 | 166 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 271 | 285 |
,| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 250 | 261 |
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
"AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Study drug includes all investigational agents (including placebo, if applicable) administered during the course of the study." (NCT00627926)
Timeframe: Baseline up to Week 48
| Intervention | participants (Number) |
|---|
| AEs | SAEs |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 354 | 24 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 361 | 33 |
,| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 362 | 31 |
Number of Subjects With Viral Relapse Planned and Viral Relapse Actual
Viral relapse was defined as having detectable HCV RNA during antiviral follow-up. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. For viral relapse, 2 analyses were performed: planned and actual. The planned analyses was measured from the end of treatment (EOT) visit to 24 weeks after the last planned dose of study treatment. The actual analyses was measured from the EOT visit to 24 weeks after the last actual dose of study treatment. (NCT00627926)
Timeframe: After last dose of study drug up to 24 week antiviral follow-up (up to Week 72)
| Intervention | participants (Number) |
|---|
| Viral Relapse Planned | Viral Relapse Actual |
|---|
| PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week | 64 | 64 |
,| Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 27 | 25 |
,| Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week | 28 | 28 |
Progression-Free Survival (PFS): Investigator-Assessment
PFS was defined as the interval from the date of randomization until the earlier date of progression or death. Progression was assessed by investigator imaging reviewers using RECIST criteria which is 20% increase in sum of longest diameter of target lesions from nadir (the lowest blood counts); measurable increase in non-target lesion; appearance of new lesions. (NCT00631371)
Timeframe: Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012)
| Intervention | months (Median) |
|---|
| Bevacizumab+Temsirolimus | 9.1 |
| Bevacizumab+ Interferon-Alfa | 10.8 |
Percentage of Participants With Objective Response (Complete Response/Partial Response): Independent-Assessment
Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30% decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent. (NCT00631371)
Timeframe: Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012)
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab+Temsirolimus | 27.0 |
| Bevacizumab+ Interferon-Alfa | 27.4 |
Progression-Free Survival (PFS): Independent-Assessment
PFS was defined as the interval from the date of randomization until the earlier date of progression or death. Progression was assessed by independent imaging reviewers using Response Evaluation Criteria in Solid Tumors (RECIST) criteria which is 20% increase in sum of longest diameter of target lesions from nadir (the lowest blood counts); measurable increase in non-target lesion; appearance of new lesions. (NCT00631371)
Timeframe: Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012)
| Intervention | months (Median) |
|---|
| Bevacizumab+Temsirolimus | 9.1 |
| Bevacizumab+ Interferon-Alfa | 9.3 |
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause, censored at the last date known alive. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). (NCT00631371)
Timeframe: Baseline until death due to any cause, assessed every 8 weeks (up to cut-off date: 19 April 2012)
| Intervention | months (Median) |
|---|
| Bevacizumab+Temsirolimus | 25.8 |
| Bevacizumab+ Interferon-Alfa | 25.5 |
Change From Baseline in Total Volume of T2 Lesions on MRI Scans of the Brain at Week 24
Change from baseline in total volume of T2 lesions on MRI scans of the Brain at week 24 was reported. (NCT00676715)
Timeframe: Baseline, Week 24
| Intervention | Cubic Millimeter (mm^3) (Mean) |
|---|
| Baseline (n= 47, 51, 53, 49) | Change at Week 24 (n= 43, 45, 46, 46) |
|---|
| Avonex | 13209.11 | 1040.06 |
,| Ocrelizumab 1000 mg | 13178.30 | -600.89 |
,| Ocrelizumab 600 mg | 13972.61 | -878.84 |
,| Placebo | 8950.84 | -112.31 |
Total Number of Gadolinium-Enhancing T1 Lesions at Weeks
Total number of gadolinium-enhancing T1 lesions at weeks were reported. (NCT00676715)
Timeframe: Weeks 4 to Week 24
| Intervention | Lesions (Mean) |
|---|
| Placebo | 8.7 |
| Ocrelizumab 600 mg | 2.5 |
| Ocrelizumab 1000 mg | 1.8 |
| Avonex | 10.3 |
Total Number of Gadolinium-Enhancing T1 Lesions Observed on MRI Scans of the Brain
Mean of total number of gadolinium-enhancing T1 lesions observed on MRI scans of the brain at Weeks 12, 16, 20, 24 was determined using average imputation method. (NCT00676715)
Timeframe: Week 12 to Week 24
| Intervention | Lesion (Mean) |
|---|
| Placebo | 5.6 |
| Ocrelizumab 600 mg | 0.6 |
| Ocrelizumab 1000 mg | 0.2 |
| Avonex | 6.9 |
Percentage of Participants Who Remained Relapse Free at Week 24
Percentage of participants who remained relapse free at week 24 were reported. (NCT00676715)
Timeframe: Week 24
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 75.9 |
| Ocrelizumab 600 mg | 85.5 |
| Ocrelizumab 1000 mg | 87.3 |
| Avonex | 77.8 |
Annualized Protocol Defined Relapse Rate at Week 24
Adjusted annualized relapse rate for geographical region. (NCT00676715)
Timeframe: Week 24
| Intervention | Number of relapses (Number) |
|---|
| Placebo | 0.557 |
| Ocrelizumab 600 mg | 0.127 |
| Ocrelizumab 1000 mg | 0.213 |
| Avonex | 0.364 |
Total Number of New Gadolinium-Enhancing T1 Lesions Observed by MRI Scans of the Brain
Total number of new gadolinium-enhancing T1 lesions observed by MRI scans of the brain were reported. (NCT00676715)
Timeframe: Weeks 4 to Week 24
| Intervention | Lesions (Mean) |
|---|
| Placebo | 5.1 |
| Ocrelizumab 600 mg | 0.8 |
| Ocrelizumab 1000 mg | 0.8 |
| Avonex | 6.2 |
Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal). TEAEs were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. Causal relationship of each TEAE to study treatment was evaluated by the investigator separately for HDI and KW2871. Regimen-limiting toxicity was defined as an HDI-related dose-limiting toxicity (DLT) that required more than 2 dose reductions of HDI during the induction phase or the first 4 weeks of the maintenance phase, or any KW2871- or regimen-related DLT. (NCT00679289)
Timeframe: From baseline through up to 17 months post-baseline
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Maximum TEAE Severity Grade 1/2 | Maximum TEAE Severity Grade 3 | Maximum TEAE Severity Grade 4 | Maximum TEAE Severity Grade 5 | Any HDI-related TEAE | Any KW2871-related TEAE | Any SAE | Any TEAE leading to withdrawal of HDI+KW2871 | Any TEAE leading to withdrawal of HDI only | Any TEAE leading to withdrawal of KW2871 only | Regimen-limiting toxicity |
|---|
| Cohort 1 | 6 | 0 | 5 | 1 | 0 | 6 | 4 | 2 | 0 | 0 | 0 | 0 |
,| Cohort 2 | 6 | 1 | 2 | 2 | 1 | 6 | 5 | 1 | 1 | 0 | 0 | 0 |
,| Cohort 3 | 24 | 2 | 20 | 1 | 1 | 24 | 7 | 7 | 3 | 1 | 1 | 2 |
Maximum KW2871 Antibody Levels in Plasma Following the First Infusion
Blood samples for pharmacokinetic (PK) measurements were collected at baseline and before and 30 minutes after the initial KW2871 infusion on Day 3. The KW2871 antibody protein in patient serum was measured using an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantitation was determined to be 100 ng/mL. (NCT00679289)
Timeframe: At Baseline and Study Day 3
| Intervention | µg/mL (Mean) |
|---|
| Cohort 1 | 3.22 |
| Cohort 2 | 5.17 |
| Cohort 3 | 9.18 |
Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]).
LTR was obtained if serum HCV RNA level at the end of 12-month follow-up was <15 IU/mL. (NCT00686517)
Timeframe: At 12 months post-treatment (treatment period either 12 weeks or 24 weeks depending on randomization).
| Intervention | participants (Number) |
|---|
| PEG-IFN 24 | 20 |
| PEG-IFN 12 | 19 |
| PEG-IFN + RVB 12 | 19 |
Virologic Response at the End of Treatment Follow-up (ETR)
"ETR was achieved if serum HCV RNA level at the end of 12 or 24 weeks~treatment (depending on treatment arm) was <15 IU/mL." (NCT00686517)
Timeframe: At the end of treatment (either 12 weeks or 24 weeks depending on randomization).
| Intervention | participants (Number) |
|---|
| PEG-IFN 24 | 26 |
| PEG-IFN 12 | 28 |
| PEG-IFN + RVB 12 | 27 |
Number of Participants With Sustained Response (SR) at the End of the 6-month Follow-up Period
SR was defined as serum Hepatitis C Virus (HCV RNA) level at the end of 6-month follow-up below 15 IU/mL. (NCT00686517)
Timeframe: Evaluated at the end of 6 months
| Intervention | participants (Number) |
|---|
| PEG-IFN 24 | 23 |
| PEG-IFN 12 | 20 |
| PEG-IFN + RVB 12 | 21 |
Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization
ALT normalization was used as a measure of biochemical response to treatment. ALT levels were assessed at each study visit by the local laboratory, and efficacy measurements at the end of treatment, at 6 and 12 months post treatment follow-up were reported. (NCT00686517)
Timeframe: Evaluated at end of treatment (either 12 weeks or 24 weeks, depending on randomization), at 6-month follow-up visit, or at 12-month follow-up visit.
| Intervention | participants (Number) |
|---|
| End of Treatment | 6-month Follow-up Period | 12-month Follow-up Period |
|---|
| PEG-IFN + RVB 12 | 32 | 28 | 23 |
,| PEG-IFN 12 | 31 | 27 | 23 |
,| PEG-IFN 24 | 28 | 31 | 27 |
Number of Participants With Rapid Virologic Response (RVR)
"Participants were considered to have RVR if serum HCV RNA level at 2 or 4~weeks of treatment was below the cut off value of the referring local~laboratory of each participating site." (NCT00686517)
Timeframe: Evaluated at 2 and 4 weeks of treatment
| Intervention | participants (Number) |
|---|
| 2 weeks after start of treatment | 4 weeks after start of treatment |
|---|
| PEG-IFN + RVB 12 | 23 | 34 |
,| PEG-IFN 12 | 25 | 35 |
,| PEG-IFN 24 | 24 | 28 |
Percentage of Participants With Sustained Virologic Response (SVR) at 24 Weeks After the End of Treatment (EOT) or Discontinuation
"SVR was defined as a viral response which was sustained at 24 weeks after the end of treatment as measured by Hepatitis C Virus Ribonucleic Acid (HCV-RNA) negativity.~HCV-RNA negativity was assessed by an reverse transcriptase polymerase chain reaction (RT-PCR) method, where a negative response was defined by a negative qualitative HCV-RNA result." (NCT00686777)
Timeframe: Measured at 24 weeks after the end of treatment (at the end of follow-up)
| Intervention | percentage of participants (Number) |
|---|
| PEG-IFN + Ribavirin | 30.7 |
Percentage of Participants With HCV-RNA Negativity at 24 Weeks of Treatment and at EOT
HCV-RNA negativity was assessed by an RT-PCR method, where a negative response was defined by a negative qualitative HCV-RNA result. (NCT00686777)
Timeframe: Measured at 24 weeks of treatment and at EOT (Treatment week 48)
| Intervention | percentage of participants (Number) |
|---|
| At 24 Weeks Treatment | At End of Treatment |
|---|
| PEG-IFN + Ribavirin | 61.3 | 66.7 |
Number of Participants Discontinuing Treatment
Prespecified adverse event discontinuance criteria included neutrophil count <500 /mm3, platelet count <50,000/mm3, and hemoglobin <8.5 g/dL. (NCT00686777)
Timeframe: From time of first treatment to Week 48
| Intervention | participants (Number) |
|---|
| Due To Decrease in Neutrophil Count | Due To Decrease in Neutrophil and Platelet Count | Due To Apathy | Due To Pleural Effusion | Due To Pregnancy of Participant's Partner | Due To No Visit | Due To Withdrawal by Subject | Total Number Discontinued |
|---|
| PEG-IFN + Ribavirin | 3 | 1 | 1 | 1 | 1 | 1 | 2 | 10 |
Number of Participants With Alanine Aminotransferase (ALT) Normalization of >16 Weeks Duration
The ALT was judged to have been normalized when the ALT level was 35 IU/L or below. (NCT00686881)
Timeframe: Week 24
| Intervention | Participants (Number) |
|---|
| PegIFN-2b | 9 |
| SNMC | 2 |
Change in Serum ALT
Change in Serum ALT concentration from baseline to week 48 (NCT00695019)
Timeframe: 48 weeks
| Intervention | U/L (Mean) |
|---|
| 500 IU qd | 7.8 |
| 500 IU Tid | 0.6 |
| Placebo | 8.6 |
Sustained Virologic Response Rate
Percentage of participants who remained HCV RNA negative throughout the study (NCT00695019)
Timeframe: 48 weeks
| Intervention | percentage of participants (Number) |
|---|
| 500 IU qd | 71.2 |
| 500 IU Tid | 62.3 |
| Placebo | 66.7 |
Relapse Rate
"Percentage of participants with a positive seum HCV RNA level at any post-baseline evaluation~Serum HCV RNA was tested using a commercially available real-time polymerase-chain-reaction (PCR) assay kit (Roche Cobas TaqMan HCV assay kit) with a limit of detection of 15 IU/ml." (NCT00695019)
Timeframe: 48 weeks
| Intervention | percentage of participants (Number) |
|---|
| 500 IU qd | 30.5 |
| 500 IU Tid | 37.7 |
| Placebo | 35.1 |
Normalization of Platelets
Percentage of participants with a low platelet count at baseline who had a normal platelet count at the end of the study (NCT00695019)
Timeframe: 48 weeks
| Intervention | percentage of participants (Number) |
|---|
| 500 IU qd | 81.0 |
| 500 IU Tid | 50.0 |
| Placebo | 41.9 |
Normalization of ALT
Percentage of participants with a normal serum ALT level at the end of the study (NCT00695019)
Timeframe: 48 weeks
| Intervention | percentage of participants (Number) |
|---|
| 500 IU qd | 71.2 |
| 500 IU Tid | 60.4 |
| Placebo | 64.9 |
Change in Social Functioning
"Change in the Social Functioning domain of the SF-36 quality-of-life questionnaire from baseline to week 48~Social Functioning (SF) scores range from 0-100, with lower scores indicating that health/emotional problems have had a greater negative impact on social activities, compared to higher scores. SF scores are calculated using a proprietary algorithm based on responses to questions #6 and #10 on the SF-36, which are 5-point likert scales about the extent to which, and the amount of time with which physical or emotional problems have interfered with social activities." (NCT00695019)
Timeframe: 48 weeks
| Intervention | change in score (Mean) |
|---|
| 500 IU qd | 21.6 |
| 500 IU Tid | 16.3 |
| Placebo | 8.8 |
Change in Serum HCV RNA Concentration
Change in serum HCV RNA concentration (log10 IU) from baseline to week 48 (NCT00695019)
Timeframe: 48 weeks
| Intervention | log10 IU (Log Mean) |
|---|
| 500 IU qd | 1.6 |
| 500 IU Tid | 1.9 |
| Placebo | 1.7 |
Change in Fibrotest Score
Change in fibrotest score from baseline to week 48 (NCT00695019)
Timeframe: 48 weeks
| Intervention | units on a scale (Mean) |
|---|
| 500 IU qd | -0.37 |
| 500 IU Tid | -0.19 |
| Placebo | -0.31 |
Number of Participants With ≥2-log10 Decrease in HCV RNA
The number of participants with at least a 2-log10 decrease from baseline in HCV RNA following 4 weeks of treatment with Placebo or Vaniprevir. (NCT00704184)
Timeframe: Baseline and Week 4
| Intervention | Number of Participants (Number) |
|---|
| Placebo + Peg-IFN/Ribavirin | 16 |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | 16 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | 19 |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | 16 |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | 17 |
Number of Participants With ≥3-log10 Decrease in HCV RNA
The number of participants with at least a 3-log10 decrease from baseline in HCV RNA following 4 weeks of treatment with Placebo or Vaniprevir. (NCT00704184)
Timeframe: Baseline and Week 4
| Intervention | Number of Participants (Number) |
|---|
| Placebo + Peg-IFN/Ribavirin | 15 |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | 16 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | 19 |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | 16 |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | 17 |
Percentage of Participants Achieving RVR
Rapid Viral Response (RVR) was declared if Hepatitis C Virus (HCV) ribonucleic acid (RNA) was undetectable at Week 4. (NCT00704184)
Timeframe: Week 4
| Intervention | Percentage of Participants (Number) |
|---|
| Placebo + Peg-IFN/Ribavirin | 5.6 |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | 75.0 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | 78.9 |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | 68.8 |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | 83.3 |
Mean Log Change From Baseline in HCV RNA
The mean changes from baseline in log10 HCV RNA in each vaniprevir group was compared against control treatment at Week 4. (NCT00704184)
Timeframe: Baseline and Week 4
| Intervention | Log10 IU/mL (Mean) |
|---|
| Placebo + Peg-IFN/Ribavirin | -3.6 |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | -6.1 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | -6.3 |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | -6.2 |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | -6.3 |
Number of Participants Discontinuing From Study Therapy Due to AEs
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study therapy, whether or not considered related to the use of the product. (NCT00704184)
Timeframe: Day 1 to Day 28
| Intervention | Participants (Number) |
|---|
| Placebo + Peg-IFN/Ribavirin | 0 |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | 0 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | 0 |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | 0 |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | 0 |
Number of Participants Experiencing an Adverse Event (AE)
The number of participants experiencing AEs in each treatment group was monitored during the Vaniprevir/Placebo treatment (Day 1 to Day 28) and safety follow-up (Day 29 to Day 42) periods. (NCT00704184)
Timeframe: Up to Day 42
| Intervention | Participants (Number) |
|---|
| Placebo + Peg-IFN/Ribavirin | 18 |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | 15 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | 18 |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | 16 |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | 18 |
Percentage of Participants Achieving SVR24 After 24 Weeks of Vaniprevir 600 mg b.i.d.
The percentage of participants achieving SVR24 after the 24-week Vaniprevir 600 mg b.i.d. regimen at Week 48 was compared to the control regimen. (NCT00704405)
Timeframe: Week 48
| Intervention | Percentage of participants (Number) |
|---|
| 24- or 48-wk Vaniprevir 600 mg + Peg-IFN/RBV | 71.1 |
| 48-wk PBO + Peg-IFN/RBV | 36.6 |
Percentage of Participants Achieving SVR24 Following Treatment With Vaniprevir 600 mg b.i.d.
The percentage of non-cirrhotic participants with undetectable Hepatits C virus (HCV) ribonucleic acid (RNA) 24 weeks after completing treatment was determined for each Vaniprevir 600 mg b.i.d. and control regimen. Results for Vaniprevir 300 mg are presented as a Secondary Outcome Measure. (NCT00704405)
Timeframe: Up to 72 weeks
| Intervention | Percentage of participants (Number) |
|---|
| 24- or 48-wk Vaniprevir 600 mg + Peg-IFN/RBV | 71.1 |
| 24-wk Vaniprevir 600 mg, 24-wk PBO + Peg-IFN/RBV | 84.2 |
| 48-wk Vaniprevir 600 mg + Peg-IFN/RBV | 78.0 |
| 48-wk PBO + Peg-IFN/RBV | 19.0 |
Percentage of Participants Achieving SVR24 Following Treatment With Vaniprevir 300 mg b.i.d.
The percentage of non-cirrhotic participants treated with Vaniprevir 300 mg b.i.d. with undetectable HCV RNA 24 weeks after completing treatment was determined. (NCT00704405)
Timeframe: 72 weeks
| Intervention | Percentage of participants (Number) |
|---|
| 48-wk Vaniprevir 300 mg + Peg-IFN/RBV | 66.7 |
| 48-wk PBO + Peg-IFN/RBV | 19.0 |
Percentage of Participants Achieving cEVR
The percentage of non-cirrhotic participants with complete early viral response (cEVR; undetectable HCV RNA at Week 12) was determined for each Vaniprevir dose. Since each of the Vaniprevir 600 mg arms had the same treatment history at this point in the study, the data were pooled for analysis. (NCT00704405)
Timeframe: Up to Week 60
| Intervention | Percentage of participants (Number) |
|---|
| 24- or 48-wk Vaniprevir 600 mg + Peg-IFN/RBV | 92.0 |
| 48-wk Vaniprevir 300 mg + Peg-IFN/RBV | 85.4 |
| PBO + Peg-IFN/RBV | 9.5 |
Number of Participants Experiencing an Adverse Event (AE)
The number of non-cirrhotic participants experiencing AEs during the active Vaniprevir/PBO treatment and 14-day follow-up periods was monitored for each treatment regimen. An AE was defined as any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a Sponsor product, whether or not considered related to the use of the product. (NCT00704405)
Timeframe: Up to 73 weeks
| Intervention | Number of participants (Number) |
|---|
| 24- or 48-wk Vaniprevir 600 mg + Peg-IFN/RBV | 38 |
| 24-wk Vaniprevir 600 mg, 24-wk PBO + Peg-IFN/RBV | 42 |
| 48-wk Vaniprevir 300 mg + Peg-IFN/RBV | 40 |
| 48-wk Vaniprevir 600 mg + Peg-IFN/RBV | 46 |
| 48-wk PBO + Peg-IFN/RBV | 41 |
Number of Participants Discontinuing From Study Treatment Due to AEs
The number of non-cirrhotic participants withdrawing from study treatment due to AEs during the active Vaniprevir/PBO treatment and 14-day follow-up periods was monitored for each treatment regimen. (NCT00704405)
Timeframe: Up to 48 weeks
| Intervention | Number of participants (Number) |
|---|
| 24- or 48-wk Vaniprevir 600 mg + Peg-IFN/RBV | 2 |
| 24-wk Vaniprevir 600 mg, 24-wk PBO + Peg-IFN/RBV | 3 |
| 48-wk Vaniprevir 300 mg + Peg-IFN/RBV | 2 |
| 48-wk Vaniprevir 600 mg + Peg-IFN/RBV | 4 |
| 48-wk PBO + Peg-IFN/RBV | 1 |
Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline
Early Virological response (EVR) was assessed at 12 weeks after treatment start (Visit 2) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR >3) to investigate the percentage of participants who achieved EVR. EVR was defined as a substantial (greater than 2 log10) decrease in viral load (measured as International Units/milliliter) and/or negative Polymerase chain reaction (PCR)-based viral load qualitative result as assessed at visit 2 of the study. (NCT00705224)
Timeframe: Week 12 after treatment start
| Intervention | Percentage of Participants (Number) |
|---|
| Genotype I | Genotype II | Genotype III | Other |
|---|
| HOMA-IR >3 | 54.0 | 6.0 | 40.0 | 0 |
,| HOMA-IR<=3 | 51.3 | 12.7 | 34.8 | 1.3 |
Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study
Sustained Virological response (SVR) was assessed at the end of the study (Visit 4) to investigate the presence or absence of SVR. SVR was defined as undetectable plasma hepatitis C virus RNA (HCV-RNA) at 24 weeks after termination of treatment. Visit 4 was considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively. (NCT00705224)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Percentage of Participants (Number) |
|---|
| Pegylated Interferon and Ribavirin | 81.2 |
Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline
Response following treatment (RFT) was assessed at the end of treatment (Visit 3) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR >3) to investigate the presence or absence of RFT. RFT was defined as undetectable plasma HCV-RNA at end of treatment. Visit 3 was considered Week 24 or Week 48 after treatment start depending on treatment duration. (NCT00705224)
Timeframe: Week 24 or 48 after treatment start
| Intervention | Percentage of Participants (Number) |
|---|
| Genotype I | Genotype II | Genotype III | Other |
|---|
| HOMA-IR >3 | 52.9 | 5.9 | 41.2 | 0 |
,| HOMA-IR<=3 | 50.6 | 12.2 | 35.9 | 1.3 |
Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline
SVR was assessed at the end of the study (Visit 4) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as Homeostasis model assessment - of insulin-resistance [HOMA-IR] >3) to investigate the presence or absence of SVR. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of treatment. Visit 4 was considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively. (NCT00705224)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Percentage of Participants (Number) |
|---|
| Genotype I | Genotype II | Genotype III | Other |
|---|
| HOMA-IR >3 | 47.5 | 7.5 | 45.0 | 0 |
,| HOMA-IR<=3 | 45.7 | 14.3 | 38.6 | 1.4 |
Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline
Virological relapse (VR) was assessed at the end of the study (Visit 4) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR >3) to investigate the percentage of participants who demonstrated VR. VR was defined as undetectable plasma HCV-RNA (RFT +) at end of treatment (Visit 3- considered Week 24 or Week 48 after treatment start depending on treatment duration), but lost RFT (considered sustained non-Responders) at end of study (Visit 4- considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively). (NCT00705224)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Percentage of Participants (Number) |
|---|
| Genotype I | Genotype II | Genotype III | Other |
|---|
| HOMA-IR >3 | 72.7 | 0 | 27.3 | 0 |
,| HOMA-IR<=3 | 83.3 | 0 | 16.7 | 0 |
Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization.
(NCT00708500)
Timeframe: At Follow-up Week 12 and at 72 weeks after randomization
| Intervention | participants (Number) |
|---|
| Follow-Up Week 12 | 72 Weeks Post Randomization |
|---|
| Boceprevir+PEG2b+RBV, Response Guided Therapy | 97 | 93 |
,| Boceprevir+PEG2b+RBV, x 44 Weeks | 105 | 105 |
,| Placebo+PEG2b+RBV, x 44 Weeks | 16 | 17 |
Number of Participants With Early Virologic Response.
Having undetectable HCV-RNA at Week 2, 4, 8, or 12 was considered Early Virologic Response. (NCT00708500)
Timeframe: At Week 2, 4, 8, or 12
| Intervention | participants (Number) |
|---|
| Week 2 | Week 4 | Week 8 | Week 12 |
|---|
| Boceprevir+PEG2b+RBV, Response Guided Therapy | 0 | 0 | 74 | 111 |
,| Boceprevir+PEG2b+RBV, x 44 Weeks | 0 | 2 | 84 | 121 |
,| Placebo+PEG2b+RBV, x 44 Weeks | 0 | 2 | 7 | 23 |
Sustained Virologic Response (SVR) Rate in the Full Analysis Set (FAS) Population.
SVR is defined as undetectable plasma hepatitis C virus RNA (HCV-RNA) at Follow-up Week 24. This outcome measure evaluates SVR after treatment with boceprevir and PEG2b plus RBV versus PEG2b plus RBV alone in participants with chronic hepatitis C (CHC) genotype 1 who failed prior treatment. (NCT00708500)
Timeframe: At Follow-up Week 24
| Intervention | Percentage of Participants (Number) |
|---|
| Placebo+PEG2b+RBV, x 44 Weeks | 21.3 |
| Boceprevir+PEG2b+RBV, Response Guided Therapy | 58.6 |
| Boceprevir+PEG2b+RBV, x 44 Weeks | 66.5 |
Sustained Virologic Response (SVR) Rate in the Modified Intent to Treat (mITT) Population.
"SVR is defined as undetectable plasma HCV-RNA at Follow-up Week 24. This outcome measure evaluates SVR after treatment with boceprevir and PEG2b plus RBV versus PEG2b plus RBV alone in participants with CHC genotype 1 who failed prior treatment.~This key secondary efficacy endpoint was added as per the second protocol amendment on 02 DEC 2009." (NCT00708500)
Timeframe: At Follow-up Week 24
| Intervention | Percentage of Participants (Number) |
|---|
| Placebo+PEG2b+RBV, x 44 Weeks | 21.8 |
| Boceprevir+PEG2b+RBV, Response Guided Therapy | 60.9 |
| Boceprevir+PEG2b+RBV, x 44 Weeks | 66.9 |
Response Duration Differences in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab
The duration of response, applied only to participants with best overall response at CR or PR, is defined as the number of days between the date of first documented response (CR or PR) and the date of the event: radiological progression as per central review or death due to underlying cancer, whichever occurs first. If no event, participant is censored at the last adequate assessment. (NCT00719264)
Timeframe: Time from first documented response date of radiological progressive disease as per independent central review, death due to underlying cancer, or last tumor assessment, reported between date of first participant randomized until 31Dec2011, cut-off date.
| Intervention | Months (Median) |
|---|
| Bevacizumab, RAD001 (Everolimus) | 13.3 |
| Bevacizumab, Interferon Alfa-2a (IFN) | 11.3 |
Duration of Exposure of RAD001 in Participants Randomized to the Treatment Combination of RAD001 and Bevacizumab
This outcome measure was assessed continuously. (NCT00719264)
Timeframe: From the date of the first participant treated until the last patient discontinued the study treatment + 28 days
| Intervention | weeks (Median) |
|---|
| Bevacizumab, RAD001 (Everolimus) | 37.0 |
Overall Survival (OS) Treatment Effect in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab
Overall survival (OS) was defined as the time of randomization to the date of death due to any cause. (NCT00719264)
Timeframe: Time from randomization to the date of death from any cause, reported between date of first participant randomized and up to 2 years after the last participant randomized (data cutoff: 30Aug2012)
| Intervention | Months (Median) |
|---|
| Bevacizumab, RAD001 (Everolimus) | 27.1 |
| Bevacizumab, Interferon Alfa-2a (IFN) | 27.1 |
Progression-free Survival (PFS) of Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab
Tumor response and disease progression were assessed using response evaluation criteria in solid tumors (RECIST), version 1.0. All target and non-target lesions identified at baseline were assessed using the same method, CT scan with contrast or MRI with contrast, throughout the trial. All scans were reviewed by independent, central radiology. Disease progression was defined as: 1) a 20% increase in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameters of all target lesions recorded at or after baseline or 2) the appearance of a new lesions or 3) the unequivocal progression of non-target lesions overall. (NCT00719264)
Timeframe: Time from randomization to the date of radiological progressive disease as per independent central review, death from any cause, or last tumor assessment, reported between date of first participant randomized until 31Dec2011, cutoff date.
| Intervention | Months (Median) |
|---|
| Bevacizumab, RAD001 (Everolimus) | 9.3 |
| Bevacizumab, Interferon Alfa-2a (IFN) | 10.0 |
Time to Definitive Deterioration of the Global Health Status and the Physical Functioning (PF) Subscale Scores of the European Organization for the Research and Treatment of Cancer (EORTC)-Core Quality of Life Questionnaire (QLQ-C30) by at Least 10%
The EORTC QLQ-C30 contains 30 items. These include five functional scales (physical, role, emotional, social and cognitive functioning), three symptom scales (fatigue, pain, nausea, and vomiting), a global health status/QoL scale, and six single items (dyspnea, diarrhea, constipation, anorexia, insomnia and financial impact). The PF subscale consists of 5 questions each scored from 1 (not at all) to 4 (very much). The score for the PF subscale and global health status range from 0 to 100, with a higher score representing a high level of functioning/high quality of life. Definitive deterioration by at least 10% is defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study. A single measure reporting a decrease of at least 10% is considered definitive only if it is the last one available for the participant. (NCT00719264)
Timeframe: Time from randomization to the date of definitive deterioration (defined as no later increase above the threshold observed during the study), or date of last assessment, reported between date of first participant randomized until 31Dec2011
| Intervention | Months (Median) |
|---|
| Global health status/QoL | Physical functioning |
|---|
| Bevacizumab, Interferon Alfa-2a (IFN) | 7.8 | 9.0 |
,| Bevacizumab, RAD001 (Everolimus) | 7.4 | 8.5 |
Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events and Deaths
Participants were monitored for adverse events, serious adverse events and deaths throughout the study. Participants were assessed continuously at each 28-day cycle. (NCT00719264)
Timeframe: From the first participant randomized until the last patient discontinued the study treatment + 28 days
| Intervention | Participants (Number) |
|---|
| Adverse events (serious and non-serious) | Serious adverse events | Deaths |
|---|
| Bevacizumab, Interferon Alfa-2a (IFN) | 180 | 76 | 95 |
,| Bevacizumab, RAD001 (Everolimus) | 179 | 79 | 93 |
Best Overall Response in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab
Overall response is defined as the number of participants having achieved confirmed Complete Response (CR) + Partial Response (PR). Confirmed CR = at least two determinations of CR at least 4 weeks apart before progression. Confirmed PR = at least two determinations of PR or better at least 4 weeks apart before progression. CR required a disappearance of all target and non-target lesions. PR required at least a 30% decrease in the sum of the longest diameters of all target lesions, taking as a reference the baseline sum of the longest diameters. Disease progression was defined as: 1) a 20% increase in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameters of all target lesions recorded at or after baseline or 2) the appearance of a new lesions or 3) the unequivocal progression of non-target lesions overall. (NCT00719264)
Timeframe: Time from first participant randomized until 31Dec2011, cutoff date.
| Intervention | Number of participants (Number) |
|---|
| Complete response (CR) | Partial response (PR) | Stable disease (SD) | Progressive disease (PD) | Unknown response | Overall objective response (CR+PR) |
|---|
| Bevacizumab, Interferon Alfa-2a (IFN) | 1 | 50 | 84 | 26 | 22 | 51 |
,| Bevacizumab, RAD001 (Everolimus) | 0 | 49 | 90 | 25 | 18 | 49 |
Number of Participants Who Completed Treatment
Treatment completion was defined as those who completed both the induction and maintenance phases. (NCT00723710)
Timeframe: Up to 1 year
| Intervention | Participants (Number) |
|---|
| Intron A | 120 |
Number of Dose Limiting Toxicities (DLTs) Observed During Dose Escalation of PEG-IFN-α-2b
"Adverse events are graded according to the National Cancer Institute's Common Toxicity Criteria (CTCAE) version 3.0. In general, grades are assigned as follows:~Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE~A dose limiting toxicity (DLT) will be defined as any grade 3 or higher hematologic toxicity or any grade 4 non-hematologic toxicity." (NCT00724061)
Timeframe: From the date that the first patient began treatment until the last patient completed the dose escalation phase (up to 12 weeks per patient)
| Intervention | dose limiting toxicities (Number) |
|---|
| PEG-IFN-alpha-2b + UV Therapy | 0 |
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on HCV genotype (1, 2, 3, 4, or 2 & 3) at baseline. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). (NCT00724464)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Participants (Number) |
|---|
| Genotype 1 | Genotype 2 | Genotype 3 | Genotype 4 | Genotype 2 & 3 |
|---|
| Pegylated Interferon Alpha-2b and Ribavirin | 81 | 28 | 146 | 30 | 1 |
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up
Sustained virological response (SVR) was assessed at the 24-week post-treatment follow-up (Visit 2). SVR was defined as undetectable plasma Hepatitis C virus Ribonucleic acid (HCV-RNA) at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). (NCT00724464)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Participants (Number) |
|---|
| Pegylated Interferon Alpha-2b and Ribavirin | 286 |
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Alanine Aminotransferase (ALT) Levels at Baseline
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on ALT levels at baseline as assessed by investigator. Normal baseline ALT level was defined as <40 IU/mL and elevated baseline ALT level was defined as >= 40 IU/mL. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). (NCT00724464)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Participants (Number) |
|---|
| Normal Baseline ALT levels | Elevated Baseline ALT levels | Missing |
|---|
| Pegylated Interferon Alpha-2b and Ribavirin | 28 | 252 | 6 |
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Study Treatment Dosage Modification
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on study treatment dosage modification: no dosage modification or any dosage modification of study treatment. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). (NCT00724464)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Participants (Number) |
|---|
| No Dosage Modification of Study Treatment | Any Dosage Modification of Study Treatment |
|---|
| Pegylated Interferon Alpha-2b and Ribavirin | 234 | 52 |
Number of Participants Who Demonstrated Virological Relapse as Assessed at 24-week Post-treatment Follow-up
Virological relapse was assessed at the 24-week post-treatment follow-up (Visit 2). Virological relapse was defined as undetectable plasma HCV-RNA at end of combination treatment (Visit 1- considered Week 24 or Week 48 after treatment start depending on treatment duration), but with positive HCV-RNA at the 24-week post treatment follow-up. (NCT00724464)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Participants (Number) |
|---|
| Pegylated Interferon Alpha-2b and Ribavirin | 23 |
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV-RNA Viral Load at Baseline
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on HCV-RNA viral load at baseline as assessed by investigator. Low viral load was defined as <400,000 International Units/milliliter (IU/mL) and high viral load was defined as >=400,000 IU/mL. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). (NCT00724464)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Participants (Number) |
|---|
| Low Viral Load | High Viral Load | Missing |
|---|
| Pegylated Interferon Alpha-2b and Ribavirin | 99 | 155 | 32 |
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Achievement of Rapid Virological Response
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on achievement of rapid virological response (RVR) where data was available. RVR was defined as negative HCV-RNA after 4 (+/- 1) weeks of treatment. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). (NCT00724464)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Participants (Number) |
|---|
| RVR at Week 4 (+/- 1) | Non-RVR at Week 4 (+/- 1) | Missing |
|---|
| Pegylated Interferon Alpha-2b and Ribavirin | 20 | 16 | 250 |
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on liver fibrosis stage, where biopsy was available, at baseline: absence, minimal, moderate, or significant as assessed by investigator. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). (NCT00724464)
Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
| Intervention | Participants (Number) |
|---|
| Absence | Minimal | Moderate | Significant | Missing |
|---|
| Pegylated Interferon Alpha-2b and Ribavirin | 83 | 27 | 15 | 4 | 157 |
Number of Participants With EOT Response by Chronic HCV Genotype (Stage 1)
"EOT response was defined as HCV-RNA negative after 24 weeks of treatment in participants with HCV-RNA Genotype 2 or 3, and after 48 weeks of treatment in participants with Genotype 1, 4, 5, or 6. If there was no EOT information or if it was marked as not done then EOT was set to no. For this analysis participants were grouped by their HCV genotype (Types 1-6); a genotype is a classification based on the differences in the genetic material within the hepatitis virus. Knowing the HCV genotype helps with deciding what type and what duration of treatment will be needed because each genotype demonstrates a different response to treatment in infected individuals." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | particpants (Number) |
|---|
| Genotype 1, 4, and 6 (N=780) | Genotype 2 and 3 (n=520) | Genotype missing (n=2) |
|---|
| Stage 1 Participants | 405 | 395 | 0 |
Number of Participants Achieving SVR by Chronic HCV Genotype (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks following EOT. Participants with no viral response information were considered viral response no. For this analysis participants were grouped by their HCV genotype (Types 1-6); a genotype is a classification based on the differences in the genetic material within the hepatitis virus. Knowing the HCV genotype helps with deciding what type and what duration of treatment will be needed because each genotype demonstrates a different response to treatment in infected individuals." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Genotype 1 (n=757) | Genotype 2 (n=172) | Genotype 3 (n=348) | Genotype 4 (n=21) | Genotype 5 (n=0) | Genotype 6 (n=2) | Genotype missing (n=2) |
|---|
| Stage 1 Participants | 298 | 126 | 207 | 5 | 0 | 2 | 0 |
Number of Participants Achieving SVR by Chronic HCV Genotype + Viral Load (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. Participants with no viral response information were considered viral response no. Viral load categories were defined as High (≥100,000 Iu/mL) or Low (<100,000 Iu/mL). For this analysis participants were grouped by their HCV genotype (Types 1-6); a genotype is a classification based on the differences in the genetic material within the hepatitis virus. Knowing the HCV genotype helps with deciding what type and what duration of treatment will be needed because each genotype demonstrates a different response to treatment in infected individuals." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Genotype 1 (n=757) | Genotype 2 (n=172) | Genotype 3 (n=348) | Genotype 4 (n=21) | Genotype 6 (n=2) | Unknown Genotype (n=2) |
|---|
| Viral Load High | 222 | 53 | 74 | 2 | 2 | 0 |
,| Viral Load Low | 42 | 4 | 14 | 3 | 0 | 0 |
,| Viral Load Missing | 34 | 69 | 119 | 0 | 0 | 0 |
Number of Participants Achieving RVR by Liver Fibrosis Stage (Stage 2)
"RVR was defined as undetectable HCV-RNA after four weeks of treatment. SVR was defined as HCV-RNA negative at 24 weeks after EOT. Participants with no viral response information were considered viral response no. Liver fibrosis stage was measured with the METAVIR scoring system (F0=no fibrosis or liver damage, F1 = beginning of liver damage with some slight scarring, F2 = moderate liver damage, scarring advancing in liver and surrounding blood vessels, F3 =significant liver damage, the liver becomes fibrotic [scarred] and connects with other scarred areas , and F4 = severe damage [cirrhosis] and liver no longer functions properly)." (NCT00724893)
Timeframe: Week 4
| Intervention | participants (Number) |
|---|
| F0 (n=28) | F1 (n=30) | F2 (n=49) | F3 (n=14) | F4 (n=27) | Could not be determined (n=206) | Other (n=34) |
|---|
| Stage 2 Participants | 4 | 9 | 8 | 2 | 1 | 29 | 3 |
Number of Participants Achieving RVR by Gender (Stage 2)
"RVR was defined as undetectable HCV-RNA after 4 weeks of treatment. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Week 4
| Intervention | participants (Number) |
|---|
| Female (n=122) | Male (n=266) |
|---|
| Stage 2 Participants | 19 | 37 |
Number of Participants Achieving SVR, Excluding Participants Who Discontinued Prior to EVR Evaluation (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. EVR was defined as either HCV-RNA detectable with a ≥2 log reduction from baseline or HCV-RNA negative at Treatment Week 12. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | Participants (Number) |
|---|
| Stage 1 Participants | 638 |
Number of Participants Achieving RVR by Chronic HCV Genotype 1 Subtype (Stage 2)
"RVR was defined as undetectable HCV-RNA after 4 weeks of treatment. SVR was defined as HCV-RNA negative at 24 weeks after EOT. Participants with no viral response information were considered viral response no. For this analysis participants were grouped by their HCV genotype subcategory (1a or 1b); subcategories are the result of a change in the genetic material in the viruses within the genotype." (NCT00724893)
Timeframe: Week 4
| Intervention | participants (Number) |
|---|
| Genotype 1a (n=147) | Genotype 1b (n=56) | Genotype unknown (n=160) | Genotype mixed (n=11) | Could not be determined (n=14) |
|---|
| Stage 2 Participants | 17 | 9 | 26 | 1 | 3 |
Number of Participants Achieving EVR by Weight (Stage 2)
"EVR was defined as either HCV-RNA undetectable with a ≥2 log reduction in HCV-RNA from baseline or HCV-RNA undetectable after 12 weeks of treatment. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Week 12
| Intervention | participants (Number) |
|---|
| 40 to <50 kg (n=16) | 50 to <64 kg (n=127) | 64 to <75 kg (n=250) | 75 to <85 kg (n=238) | >=85 kg (n=490) | Weight unknown (n=7) |
|---|
| Stage 2 Participants | 9 | 87 | 164 | 143 | 283 | 4 |
Number of Participants Achieving EVR by Race (Stage 2)
"EVR was defined as either HCV-RNA undetectable with a ≥2 log reduction in HCV-RNA from baseline or HCV-RNA undetectable after 12 weeks of treatment. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Week 12
| Intervention | participants (Number) |
|---|
| Aboriginal peoples/Metis (n=13) | Asian (n=54) | Black (n=20) | Caucasian (n=1002) | Hispanic (n=4) | Other (n=35) |
|---|
| Stage 2 Participants | 6 | 42 | 8 | 609 | 4 | 21 |
Number of Participants Achieving EVR by Liver Fibrosis Stage (Stage 2)
"EVR was defined as either HCV-RNA undetectable with a ≥2 log reduction in HCV-RNA from baseline or HCV-RNA undetectable after 12 weeks of treatment.SVR was defined as HCV-RNA negative at 24 weeks after EOT. Participants with no viral response information were considered viral response no. Liver fibrosis stage was measured with the METAVIR scoring system (F0=no fibrosis or liver damage, F1 = beginning of liver damage with some slight scarring, F2 = moderate liver damage, scarring advancing in liver and surrounding blood vessels, F3 =significant liver damage, the liver becomes fibrotic [scarred] and connects with other scarred areas , and F4 = severe damage [cirrhosis] and liver no longer functions properly)." (NCT00724893)
Timeframe: Week 12
| Intervention | participants (Number) |
|---|
| F0 (n=66) | F1 (n=144) | F2 (n=212) | F3 (99) | F4 (n=110) | Could not be determined (n=463) | Other (n=34) |
|---|
| Stage 2 Participants | 49 | 95 | 133 | 62 | 53 | 280 | 18 |
Number of Participants Achieving EVR by Gender (Stage 2)
"EVR was defined as either HCV-RNA undetectable with a ≥2 log reduction in HCV-RNA from baseline or HCV-RNA undetectable after 12 weeks of treatment. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Week 12
| Intervention | participants (Number) |
|---|
| Female (n=346) | Male (n=782) |
|---|
| Stage 2 Participants | 227 | 463 |
Number of Participants Achieving EVR by Chronic HCV Genotype 1 Subtype (Stage 2)
"EVR was defined as either HCV-RNA undetectable with a ≥2 log reduction in HCV-RNA from baseline or HCV-RNA undetectable after 12 weeks of treatment.SVR was defined as HCV-RNA negative at 24 weeks after EOT. Participants with no viral response information were considered viral response no. For this analysis participants were grouped by their HCV genotype subcategory (1a or 1b); subcategories are the result of a change in the genetic material in the viruses within the genotype." (NCT00724893)
Timeframe: Week 12
| Intervention | participants (Number) |
|---|
| Genotype 1a (n=176) | Genotype 1b (n=74) | Genotype unknown (n=850) | Genotype mixed (n=14) | Could not be determined (n=14) |
|---|
| Stage 2 Participants | 106 | 51 | 518 | 8 | 7 |
The Number of Participants Achieving Viral Response at 12 Weeks After EOT, Excluding Participants Who Discontinued Prior to EVR Evaluation and Participants With Missing Data (Stage 1)
"Viral response was defined as negative HCV-RNA; evaluation was done 12 weeks (window 10-14 weeks) after EOT. EVR was defined as either HCV-RNA detectable with a ≥2 log reduction from baseline or HCV-RNA negative at Treatment Week 12. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 62 weeks
| Intervention | Participants (Number) |
|---|
| Stage 1 Participants | 679 |
Number of Participants Achieving SVR by Weight (Stage 2)
"SVR was defined as HCV-RNA negative at 24 weeks after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| 40 to <50 kg (n=16) | 50 to <64 (n=127) | 64 to <75 kg (n=250) | 75 to >85 kg (n=238) | >=85 kg (n=490) | Weight unknown (n=7) |
|---|
| Stage 2 Participants | 6 | 59 | 115 | 93 | 193 | 2 |
Number of Participants Achieving SVR by Weight (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| 40 to <50 kg (n=21) | 50 to <64 kg (n=160) | 64 to <75 kg (n=297) | 75 to <85 kg (n=283) | >85 kg (n=541) |
|---|
| Stage 1 Participants | 10 | 82 | 158 | 137 | 251 |
Number of Participants Achieving SVR by Chronic HCV Genotype 1 Subtype (Stage 2)
"SVR was defined as HCV-RNA negative at 24 weeks after EOT. Participants with no viral response information were considered viral response no. For this analysis participants were grouped by their HCV genotype subcategory (1a or 1b); subcategories are the result of a change in the genetic material in the viruses within the genotype." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Genotype 1a (n=176) | Genotype 1b (n=74) | Genotype Unknown (n=850) | Genotype mixed (n=14) | Could not be determined (n=14) |
|---|
| Stage 2 Participants | 58 | 37 | 364 | 5 | 4 |
Number of Participants Achieving SVR by EVR Type (Stage 1)
"EVR was defined as either HCV-RNA detectable with a ≥2 log reduction from baseline or HCV-RNA negative after 12 weeks of treatment. SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| EVR by ≥2 log reduction from baseline (n=78) | EVR by HCV-RNA negative (n=389) | EVR missing (n=6) |
|---|
| Stage 1 Participants | 15 | 253 | 2 |
Number of Participants Achieving SVR by Gender (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Female (n=432) | Male (n=870) |
|---|
| Stage 1 Participants | 241 | 397 |
Number of Participants Achieving SVR by Gender (Stage 2)
"SVR was defined as HCV-RNA negative at 24 weeks after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Female (n=346) | Male (n=782) |
|---|
| Stage 2 Participants | 167 | 301 |
Number of Participants Achieving SVR by Human Immunodeficiency Virus (HIV) Status (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| HIV positive (n=11) | HIV negative (n=1075) | HIV status not done (n=216) |
|---|
| Stage 1 Participants | 3 | 543 | 92 |
Number of Participants Achieving SVR by Liver Fibrosis Score (Stage 2)
"SVR was defined as HCV-RNA negative at 24 weeks after EOT. Participants with no viral response information were considered viral response no. Liver fibrosis stage was measured with the METAVIR scoring system (F0=no fibrosis or liver damage, F1 = beginning of liver damage with some slight scarring, F2 = moderate liver damage, scarring advancing in liver and surrounding blood vessels, F3 =significant liver damage, the liver becomes fibrotic [scarred] and connects with other scarred areas , and F4 = severe damage [cirrhosis] and liver no longer functions properly)." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| F0 (n=66) | F1 (n=144) | F2 (n=212) | F3 (n=99) | F4 (n=110) | Could not be determined (n=463) | Other (n=34) |
|---|
| Stage 2 Participants | 36 | 72 | 94 | 35 | 35 | 187 | 9 |
Number of Participants Achieving SVR by Liver Fibrosis Stage (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. Participants with no viral response information were considered viral response no. Liver fibrosis stage was measured with the METAVIR scoring system (F0=no fibrosis or liver damage, F1 = beginning of liver damage with some slight scarring, F2 = moderate liver damage, scarring advancing in liver and surrounding blood vessels, F3 = significant liver damage, the liver is fibrotic [scarred] and connects with other scarred areas, and F4 = severe damage [cirrhosis] and liver no longer functions properly)." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| F0 (n=59) | F1 (n=159) | F2 (n=216) | F3 (n=128) | F4 (n=111) | Fibrosis stage unknown (n=629) |
|---|
| Stage 1 Participants | 33 | 85 | 90 | 49 | 38 | 343 |
Number of Participants Achieving SVR by Race (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Asian (n=78) | Black (n=18) | Caucasian (N=1110) | Hispanic (n=11) | Other (n=85) |
|---|
| Stage 1 Participants | 59 | 9 | 524 | 4 | 42 |
Number of Participants Achieving SVR by Race (Stage 2)
"SVR was defined as HCV-RNA negative at six months after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Aboriginal peoples/Metis (n=13) | Asians (n=54) | Black (n=20) | Caucasian (n=1002) | Hispanic (n=4) | Other (n=35) |
|---|
| Stage 2 Participants | 4 | 37 | 5 | 407 | 4 | 11 |
Number of Participants Achieving SVR by Viral Load (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. Participants with no viral response information were considered viral response no. Viral load categories were defined as High (≥100,000 Iu/mL) or Low (<100,000 Iu/mL)." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Viral load high (n=836) | Viral load low (n=109) | Viral load missing (n=357) |
|---|
| Stage 1 Participants | 353 | 63 | 222 |
Number of Participants Achieving Viral Response at Any Evaluation Point (Stage 1)
"This is a measure of the number of participants achieving a viral response (negative hepatitis C virus ribonucleic acid [HCV-RNA]) at either of the follow-up evaluation time points (12 weeks [window 10-14 weeks] or ≥22 weeks after the end of treatment (EOT). Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Stage 1 Participants | 685 |
Percentage of Compliance for Participants Achieving SVR Based on Medication Adherence Questionnaire (MAQ) (Stage 2)
"Compliance was defined as participants taking ≥80% versus <80% of their doses; compliance ≥80% was derived from participants who answered always or most of the time to Questions 4 (How often do you stick to your medication schedule for your Ribavirin?) and 5 (How often do you stick to your medication schedule for your Redipen [peginterferon] injections?) of the 6-question compliance questionnaire. Percentages are based on the total number of participants within each compliance category. SVR was defined as HCV-RNA negative at 24 weeks after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | percentage of participants (Number) |
|---|
| Compliance < 80% (n=10) | Compliance ≥80% (n=304) |
|---|
| Stage 2 Participants | 40.0 | 39.1 |
Number of Participants Achieving Sustained Viral Response (SVR) (Stage 1)
"This is a measure of the number of participants who achieved SVR, defined as HCV-RNA negative at ≥22 weeks after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | Participants (Number) |
|---|
| Stage 1 Participants | 638 |
Number of Participants Achieving RVR Who Achieved SVR (Stage 2)
"RVR was defined as undetectable HCV-RNA after four weeks of treatment. SVR was defined as HCV-RNA negative at 24 weeks after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Week 4
| Intervention | participants (Number) |
|---|
| Stage 2 Participants | 35 |
Number of Participants Achieving Rapid Virologic Response (RVR) (Stage 2)
"RVR was defined as undetectable HCV-RNA after 4 weeks of treatment (window of 2 to 6 weeks). Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Week 4
| Intervention | participants (Number) |
|---|
| Stage 2 Participants | 56 |
Number of Participants Achieving EVR (Stage 2)
"EVR was defined as either HCV-RNA undetectable with a ≥2 log reduction in HCV-RNA from baseline or HCV-RNA undetectable after 12 weeks of treatment. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Week 12
| Intervention | participants (Number) |
|---|
| Stage 2 Participants | 690 |
Relapse Rate by HCV Genotype (Stage 1)
"The relapse rate was calculated with these parameters: EOT yes, EVR evaluation valid, and ≥22 weeks of follow-up data. There were no imputations for EOT or SVR. Participants with no viral response information were considered viral response no. For this analysis participants were grouped by their HCV genotype (Types 1-6); a genotype is a classification based on the differences in the genetic material within the hepatitis virus. Knowing the HCV genotype helps with deciding what type and what duration of treatment will be needed because each genotype demonstrates a different response to treatment in infected individuals." (NCT00724893)
Timeframe: Up to 48 weeks
| Intervention | Percentage of Participants (Number) |
|---|
| Genotype 1 (n=251) | Genotype 2 (n=123) | Genotype 3 (n=217) | Genotype 4 (n=5) | Genotype 6 (n=2) |
|---|
| Stage 1 Participants | 11.5 | 3.2 | 9.7 | 40.0 | 0 |
The Number of Participants Achieving Viral Response at 12 Weeks After EOT by Chronic HCV Genotype (Stage 1)
"Viral response was defined as negative HCV-RNA; evaluation was done 12 weeks (window 10-14 weeks) after EOT. Participants with no viral response information were considered viral response no. For this analysis participants were grouped by their HCV genotype (Types 1-6); a genotype is a classification based on the differences in the genetic material within the hepatitis virus. Knowing the HCV genotype helps with deciding what type and what duration of treatment will be needed because each genotype demonstrates a different response to treatment in infected individuals." (NCT00724893)
Timeframe: Up to 62 weeks
| Intervention | Participants (Number) |
|---|
| Genotype 1 (n=757) | Genotype 2 (n=172) | Genotype 3 (n=348) | Genotype 4 (n=21) | Genotype 5 (n=0) | Genotype 6 (n=2) | Genotype unknown (n=2) |
|---|
| Stage 1 Participants | 308 | 129 | 215 | 6 | 0 | 2 | 0 |
The Number of Participants Achieving Viral Response at 12 Weeks After EOT by Liver Fibrosis Stage (Stage 1)
"Viral response was defined as negative HCV-RNA; evaluation was done 12 weeks (window 10-14 weeks) after EOT. Participants with no viral response information were considered viral response no. Liver fibrosis stage was measured with the METAVIR scoring system (F0=no fibrosis or liver damage, F1 = beginning of liver damage with some slight scarring, F2 = moderate liver damage, scarring advancing in liver and surrounding blood vessels, F3 =significant liver damage, the liver becomes fibrotic [scarred] and connects with other scarred areas, and F4 = severe damage [cirrhosis] and liver no longer functions properly)." (NCT00724893)
Timeframe: Up to 62 weeks
| Intervention | Participants (Number) |
|---|
| F0 (n=59) | F1 (n=159) | F2 (n=216) | F3 (n=128) | F4 (n=111) | Fibrosis stage unknown (n=629) |
|---|
| Stage 1 Participants | 34 | 89 | 95 | 51 | 40 | 351 |
Number of Participants Achieving EVR (Stage 1)
"EVR was defined as either HCV-RNA detectable with a ≥2 log reduction from baseline or HCV-RNA negative after 12 weeks of treatment. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: From Week 10 to Week 14
| Intervention | participants (Number) |
|---|
| Stage 1 Participants | 473 |
Number of Participants Achieving EVR Who Achieved SVR (Stage 2)
"EVR was defined as either HCV-RNA undetectable with a ≥2 log reduction in HCV-RNA from baseline or HCV-RNA undetectable after 12 weeks of treatment. SVR was defined as HCV-RNA negative at 24 weeks after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Week 12
| Intervention | participants (Number) |
|---|
| Stage 2 Participants | 399 |
Number of Participants Achieving RVR by Weight (Stage 2)
"RVR was defined as undetectable HCV-RNA after 4 weeks of treatment. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Week 4
| Intervention | participants (Number) |
|---|
| 40 to <50 kg (n=3) | 50-<64 kg (n=40) | 64 to <75 kg (n=83) | 75 to <85 kg (n=86) | >=85 kg (n=169) | Weight unknown (n=7) |
|---|
| Stage 2 Participants | 0 | 8 | 9 | 11 | 27 | 1 |
Number of Participants Achieving RVR by Race (Stage 2)
"RVR was defined as undetectable HCV-RNA after 4 weeks of treatment (window of 2 to 6 weeks). Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Week 4
| Intervention | participants (Number) |
|---|
| Aboriginal peoples/Metis (n=10) | Asian (n=19) | Black (n=8) | Caucasian (n=343) | Hispanic (n=1) | Other (n=7) |
|---|
| Stage 2 Participants | 0 | 6 | 0 | 47 | 0 | 3 |
Number of Participants Achieving Viral Response at 12 Weeks After EOT, Excluding Participants Who Discontinued Prior to EVR Evaluation (Stage 1)
"Viral response was defined as negative HCV-RNA. EVR was defined as either HCV-RNA detectable with a ≥2 log reduction from baseline or HCV-RNA negative at Treatment Week 12. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 62 weeks
| Intervention | Participants (Number) |
|---|
| Stage 1 Participants | 660 |
Number of Participants Achieving Viral Response at 12 Weeks After EOT (Stage 1)
"This is a measure of the number of participants achieving a viral response (negative HCV-RNA) at 12 weeks (window 10-14 weeks) after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 62 weeks
| Intervention | Participants (Number) |
|---|
| Stage 1 Participants | 660 |
The Number of Participants Achieving SVR Excluding Participants Who Discontinued Prior to EVR Evaluation and Participants With Missing Data (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. EVR was defined as either HCV-RNA detectable with a ≥2 log reduction from baseline or HCV-RNA negative at Treatment Week 12. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Stage 1 Participants | 612 |
Number of Participants With End of Treatment (EOT) Response (Stage 1)
"EOT response was defined as HCV-RNA negative after 24 weeks of treatment in participants with HCV Genotype 2 or 3, and after 48 weeks of treatment in participants with Genotype 1, 4, 5, or 6. If there was no EOT information or if it was marked as not done then EOT was set to no." (NCT00724893)
Timeframe: Up to 48 weeks
| Intervention | participants (Number) |
|---|
| Stage 1 Participants | 800 |
Number of Participants Discontinued From Study Treatment Due to Adverse Events (Stage 1 and Stage 2)
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment (NCT00724893)
Timeframe: Up to 48 weeks
| Intervention | participants (Number) |
|---|
| Stage 1 Participants | 76 |
| Stage 2 Participants | 142 |
Number of Participants Achieving Viral Response at Any Evaluation Point, Excluding Participants Who Discontinued Treatment Prior to Early Virologic Response (EVR) Evaluation (Stage 1)
"Viral response was defined as negative HCV-RNA. EVR was defined as either HCV-RNA detectable with a ≥2 log reduction from baseline or HCV-RNA negative at Treatment Week 12. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | Participants (Number) |
|---|
| Stage 1 Participants | 685 |
Number of Participants Discontinued From Study Drug Due to Adverse Events by Chronic HCV Genotype (Stage 1)
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. For this analysis participants were grouped by their HCV genotype (Types 1-6); a genotype is a classification based on the differences in the genetic material within the hepatitis virus. Knowing the HCV genotype helps with deciding what type and what duration of treatment will be needed because each genotype demonstrates a different response to treatment in infected individuals. (NCT00724893)
Timeframe: Up to 48 weeks
| Intervention | Participants (Number) |
|---|
| Genotypes 1, 4, and 6 (n=780) | Genotype 2 and 3 (n=520) |
|---|
| Stage 1 Participants | 52 | 24 |
Number of Participants Achieving SVR by Weight + Chronic HCV Genotype (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. Participants with no viral response information were considered viral response no. For this analysis participants were grouped by their HCV genotype (Types 1-6); a genotype is a classification based on the differences in the genetic material within the hepatitis virus. Knowing the HCV genotype helps with deciding what type and what duration of treatment will be needed because each genotype demonstrates a different response to treatment in infected individuals." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Genotype 1 (n=757) | Genotype 2 (n=172) | Genotype 3 (n=348) | Genotype 4 (n=21) | Genotype 6 (n=2) | Genotype unknown (n=2) |
|---|
| >85 kg | 118 | 58 | 75 | 0 | 0 | 0 |
,| 40 to <50 kg | 4 | 5 | 1 | 0 | 0 | 0 |
,| 50 to <64 kg | 39 | 11 | 31 | 0 | 1 | 0 |
,| 64 to <75 kg | 76 | 26 | 53 | 2 | 1 | 0 |
,| 75 to <85 kg | 61 | 26 | 47 | 3 | 0 | 0 |
Number of Participants Achieving SVR by Chronic HCV Genotype + Liver Fibrosis Stage (Stage 1)
"SVR was defined as HCV-RNA negative at ≥22 weeks after EOT. Participants with no viral response information were considered viral response no. Liver fibrosis stage was measured with the METAVIR scoring system (F0=no fibrosis or liver damage, F1 = beginning of liver damage with some slight scarring, F2 = moderate liver damage, scarring advancing in liver and surrounding blood vessels, F3 =significant liver damage, the liver becomes fibrotic [scarred] and connects with other scarred areas, and F4 = severe damage [cirrhosis] and liver no longer functions properly). For this analysis participants were grouped by their HCV genotype (Types 1-6); a genotype is a classification based on the differences in the genetic material within the hepatitis virus. Knowing the HCV genotype helps with deciding what type and what duration of treatment will be needed because each genotype demonstrates a different response to treatment in infected individuals." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Genotype 1 (n=757) | Genotype 2 (n=172) | Genotype 3 (n=348) | Genotype 4 (n=21) | Genotype 6 (n=2) | Unknown Genotype (n=2) |
|---|
| Stage F0 | 21 | 4 | 8 | 0 | 0 | 0 |
,| Stage F1 | 55 | 17 | 13 | 0 | 0 | 0 |
,| Stage F2 | 64 | 13 | 13 | 0 | 0 | 0 |
,| Stage F3 | 28 | 9 | 10 | 0 | 2 | 0 |
,| Stage F4 | 25 | 2 | 9 | 2 | 0 | 0 |
,| Unknown Stage | 105 | 81 | 154 | 3 | 0 | 0 |
Number of Participants Achieving SVR (Stage 2)
"SVR was defined as HCV-RNA negative at six months after EOT. Participants with no viral response information were considered viral response no." (NCT00724893)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Stage 2 Participants | 468 |
Number of Participants With EVR by Selected Chronic HCV Genotypes (Stage 1)
"EVR was defined as either HCV-RNA detectable with a ≥2 log reduction from baseline or HCV-RNA negative at TW12. Participants with no viral response information were considered viral response no. For this analysis participants were grouped by their HCV genotype (Types 1-6); a genotype is a classification based on the differences in the genetic material within the hepatitis virus. Knowing the HCV genotype helps with deciding what type and what duration of treatment will be needed because each genotype demonstrates a different response to treatment in infected individuals." (NCT00724893)
Timeframe: Week 12
| Intervention | Participants (Number) |
|---|
| Genotype 1 (n=757) | Genotypes 1,4, and 6 (n=780) |
|---|
| Stage 1 Participants | 461 | 473 |
Number of Participants Who Received Antiviral Treatment Who Were Also on Substitution Therapy
This measure was the number of all of the participants who received antiviral treatment who also received substitution therapy. (NCT00725751)
Timeframe: Day 1
| Intervention | participants (Number) |
|---|
| All Participants | 90 |
Number of Participants Who Completed Treatment With PegIFN-2b/Ribavirin
For participants with Genotype 1 or 4 completion of treatment was at Week 48; for participants with Genotype 2, 3, or 1 with low viral load or rapid virologic response, completion of therapy was at Week 24. (NCT00725751)
Timeframe: 24 to 48 weeks
| Intervention | participants (Number) |
|---|
| PegIFN-2b/Ribavirin With Substitution Therapy | 56 |
| PegIFN-2b/Ribavirin Without Substitution Therapy | 150 |
Number of Participants Who Achieved Sustained Virologic Response (SVR)
SVR was defined as a hepatitis C virus (HCV) ribonucleic acid (RNA) value below the limit of detection by polymerase chain reaction (PCR) analysis. For participants with Genotype 1 or 4 completion of treatment was at Week 48; for participants with Genotype 2, 3, or 1 with low viral load or rapid virologic response, completion of therapy was at Week 24. (NCT00725751)
Timeframe: 24 weeks after the end of treatment (i.e. 48 or 72 weeks depending on genotype)
| Intervention | participants (Number) |
|---|
| PegIFN-2b/Ribavirin With Substitution Therapy | 42 |
| PegIFN-2b/Ribavirin Without Substitution Therapy | 111 |
Number of Participants Who Tolerated Treatment With PegIntron 1.5 mcg/kg/Week + Rebetol 10.6 mg/kg/Week
Tolerability of the treatment was measured by number of participants with complete treatment. (NCT00726557)
Timeframe: Assessed at the end of treatment
| Intervention | participants (Number) |
|---|
| Participants Who Tolerated Treatment | 118 |
Number of Drug-substituted Participants Who Achieved Sustained Virological Response (SVR) With PegIntron 1.5 μg/kg/Week and Rebetol (10.6 mg/kg/Day) in Substitution Centers Under Routine Conditions
Participants who achieved SVR (sustained virological response) at the end of treatment (24 weeks for genotypes 2,3 and 48 weeks for genotypes 1,4) were analyzed for sustained response at the end of the follow-up period (24 weeks after end of treatment). SVR is defined as having negative HCV-RNA (hepatitis C virus ribonucleic acid). (NCT00726557)
Timeframe: End of Follow-up (Week 48 or Week 72, depending on genotype)
| Intervention | Participants (Number) |
|---|
| Opioid substitution with methadone (n=52) | Opioid substitution with levo-methadone (n=13) | Opioid substitution with buprenorphine (n=26) | Opioid substitution with other medication (n=1) | No opioid substitution medication (n=9) |
|---|
| Participants With Negative HCV-RNA at End of Treatment | 49 | 10 | 23 | 0 | 9 |
Time to Progression (TTP) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Time to progression was defined as the time between date of randomization and date of documented progression. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event (including participants who died before progressive disease) were censored at the date of last follow-up for progression or date of last available tumor measurement if no follow-up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization. (NCT00738530)
Timeframe: Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
| Intervention | months (Median) |
|---|
| Bevacizumab + IFN-Alfa-2A | 10.2 |
| Placebo + IFN-Alfa-2A | 5.5 |
Time to Treatment Failure (TTF) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Time to treatment failure was defined as the time between the date of randomization and the date of insufficient therapeutic response (including disease progression), death, withdrawal of treatment due to adverse events or laboratory abnormality, or withdrawal of informed consent. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event were censored at the date of last tumor assessment or last treatment administration, whichever occurred last. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization. (NCT00738530)
Timeframe: Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
| Intervention | months (Median) |
|---|
| Bevacizumab + IFN-Alfa-2A | 8.1 |
| Placebo + IFN-Alfa-2A | 4.5 |
Percentage of Participants With Best Overall Response According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Best response recorded from the start of treatment until disease progression. Based on assessment of CR, PR, stable disease (SD), or progressive disease (PD), according to mRECIST. CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: >=30% decrease under baseline of the sum of the LD of all target lesions. CR and PR persist on repeat imaging study at least 4 weeks after initial documentation. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Reference is the smallest sum LD. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. (NCT00738530)
Timeframe: Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
| Intervention | percentage of participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Missing (no response assessment) |
|---|
| Bevacizumab + IFN-Alfa-2A | 1.6 | 30.7 | 44.4 | 20.6 | 2.6 |
,| Placebo + IFN-Alfa-2A | 2.4 | 10.0 | 50.5 | 33.2 | 3.8 |
Overall Survival (OS) Duration
Duration of survival was defined as the time between the date of randomization and date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive. Kaplan-Meier estimates were used for analysis. (NCT00738530)
Timeframe: Baseline until death (up to 4.25 years)
| Intervention | months (Median) |
|---|
| Bevacizumab + IFN-Alfa-2A | 23.3 |
| Placebo + IFN-Alfa-2A | 21.3 |
Percentage of Participants Who Died
(NCT00738530)
Timeframe: Baseline up to 4.25 years
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab + IFN-Alfa-2A | 67.3 |
| Placebo + IFN-Alfa-2A | 69.6 |
Percentage of Participants With Disease Progression or Death
Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. (NCT00738530)
Timeframe: Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab + IFN-Alfa-2A | 92.0 |
| Placebo + IFN-Alfa-2A | 92.5 |
Percentage of Participants With Objective Response According to mRECIST
Objective response referred to participants with complete response (CR) or partial response (PR). CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: greater than or equal to (>=) 30% decrease in sum of the longest diameter (LD) of all target lesions taking as reference the screening sum LD. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments that should have been performed no less than 4 weeks after the criteria for response were first met. Longer intervals as determined by the study protocol were also appropriate. (NCT00738530)
Timeframe: Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab + IFN-Alfa-2A | 32.4 |
| Placebo + IFN-Alfa-2A | 12.5 |
Percentage of Participants With Treatment Failure
Treatment failure is defined as insufficient therapeutic response (including disease progression), death, withdrawal of treatment due to adverse events or laboratory abnormality, or withdrawal of informed consent. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. (NCT00738530)
Timeframe: Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab + IFN-Alfa-2A | 90.5 |
| Placebo + IFN-Alfa-2A | 91.6 |
Progression Free Survival (PFS) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Progression-free survival was defined as the time between the date of randomization and the first date of documented progression or date of death due to any cause, whichever occurred first. Tumor assessment was performed using modified RECIST. Progressive disease was defined as at least a 20 percentage(%) increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event were censored at the date of last follow-up for progression or date of last available tumor measurement if no follow-up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization. (NCT00738530)
Timeframe: Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
| Intervention | months (Median) |
|---|
| Bevacizumab + IFN-Alfa-2A | 10.2 |
| Placebo + IFN-Alfa-2A | 5.5 |
Number of Participants With Disease Recurrence
Number of participants with disease recurrence was being measured. (NCT00749684)
Timeframe: Throughout 12 months of treatment and 24 months of follow-up
| Intervention | participants (Number) |
|---|
| Adults With Malignant Melanoma at High Risk of Relapse | 52 |
Relapse Free Survival Time
Median time to recurrence according to Kaplan Maier evaluation (NCT00749684)
Timeframe: Throughout 12 months of treatment and 24 months of follow-up
| Intervention | months (Median) |
|---|
| Adults With Malignant Melanoma at High Risk of Relapse | 54.1 |
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence in a participant that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not related to the investigational product. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. (NCT00784836)
Timeframe: Planned for up to 18 months plus 30 days; actual study duration was 111 days.
| Intervention | participants (Number) |
|---|
| AEs | SAEs |
|---|
| Avonex | 3 | 0 |
Time to Progression
Patients were censored if they did not progress, stopped particiaption due to an adverse event, or withdrew consent following the start of study treatment. Response was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) guidelines version 1.0. Per RECIST v1.0, Progressive Disease (PD) is defined as a measurable increase in smallest diameter of any target or non-target lesion, or the appearance of new lesions, since baseline. (NCT00786643)
Timeframe: From date of study treatment start until date of first documented progression or date of death from any cause, whichever came first, assessed up to 15 months
| Intervention | Months (Median) |
|---|
| Stratum 1 | 5.5263 |
| Stratum 2 | 3.9145 |
Best Response (BR)
BR is recorded from start of treatment until progressive disease (PD). Imaging was repeated by same technique after every 4 cycles of treatment. Response was evaluated per Response Evaluation Criteria In Solid Tumors (RECIST) guidelines version 1.0. Per RECIST v1.0 and CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; PD, increase in existing lesions or new lesions. (NCT00786643)
Timeframe: After every 4 cycles of treatment (approximately every 56 days for up to about 280 days)
| Intervention | Participants (Number) |
|---|
| Complete response (CR) | Partial response (PR) | Stable disease (SD) | Progressive disease (PD) | Not evaluable (NE) |
|---|
| Stratum 1 | 0 | 6 | 7 | 6 | 1 |
,| Stratum 2 | 0 | 3 | 15 | 6 | 4 |
Early Response Rate (RR) (Stratum 1 Only)
Early RR evaluated in stratum 1 to see if bevacizumab (bev) would be added to GFL treatment (tx). Patients with stable disease (SD) pre 5th cycle of tx had bev added. Response was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Per RECIST and CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in sum of longest diameter (LD) of target lesions; SD, neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD), increase in existing lesions or new lesions. (NCT00786643)
Timeframe: After 4 cycles of treatment (approximately 56 days)
| Intervention | Participants (Number) |
|---|
| Complete response (CR) | Partial response (PR) | Stable disease (SD) | Progressive disease (PD) | Not evaluable (NE) |
|---|
| Stratum 1 | 0 | 5 | 7 | 6 | 2 |
All Cause Mortality Rate at 6 Months
A long-term secondary efficacy variable was all cause mortality at 6 months following commencement of treatment (NCT00789685)
Timeframe: 6 months following commencement of therapy
| Intervention | percentage of patients who died (Number) |
|---|
| Safety Population | 11.1 |
Clinically Significant Treatment Emergent Events
Treatment-emergent adverse events (TEAEs) in safety population (NCT00789685)
Timeframe: From first dose up until Day 28
| Intervention | Number of patients (Number) |
|---|
| TEAEs | Severe TEAEs | Serious TEAEs | Drug-Related TEAEs | Serious Drug-Related TEAEs | TEAEs leading to withdrawal |
|---|
| Safety Population | 37 | 30 | 22 | 20 | 8 | 6 |
All Cause Mortality at Day 28
The primary efficacy variable was all cause mortality at Day 28 following commencement of treatment (NCT00789685)
Timeframe: 28 days following commencement of therapy
| Intervention | percentage of patients who died (Number) |
|---|
| Safety Population | 8.1 |
OS - Percentage of Participants With an Event
OS was defined as the time period from the first bevacizumab infusion to death from any cause. Censoring at start of any subsequent antineoplastic therapy was not performed. (NCT00796757)
Timeframe: Day 0, every 2 weeks until disease progression or end of treatment visit (28 days after last bevacizumab infusion, every 3 months during follow-up, or a maximum of 2 years from enrollment of last participant
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab + Interferon | 41.8 |
Percentage of Participants With a Best Overall Response of Complete Reponse (CR) or Partial Response (PR)
Percentage of participants with objective response, termed responders, based assessment of confirmed CR or confirmed PR according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses were those that persisted on repeat imaging study greater than or equal to (≥)4 weeks after initial documentation of response. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than [<]10 millimeters [mm]). No new lesions. PR was defined as ≥30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. (NCT00796757)
Timeframe: Baseline, every 8 weeks to Week 32 then every 12 weeks to disease progression or a maximum of 2 years from enrollment of last participant
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab + Interferon | 28.8 |
OS - Time to Event
OS was defined as the time period from the first bevacizumab infusion to death from any cause. Censoring at start of any subsequent antineoplastic therapy was not performed. (NCT00796757)
Timeframe: Day 0, every 2 weeks until disease progression or end of treatment visit (28 days after last bevacizumab infusion, every 3 months during follow-up, or a maximum of 2 years from enrollment of last participant
| Intervention | months (Median) |
|---|
| Bevacizumab + Interferon | 30.7 |
EQ-5D - Visual Analog Scale (VAS)
EQ-5D: participant-rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 millimeters (mm) (best imaginable health state); higher scores indicate a better health state. Participants were asked to rate their health state and mark the line; the distance from the left edge was recorded. For change from baseline a negative value represents a worsening in the health state and a positive value represents an improvement in the health state. (NCT00796757)
Timeframe: Screening/Baseline, Cycle 7, Cycle 25, Cycle 43, Cycle 61, and EOT
| Intervention | mm (Mean) |
|---|
| Baseline (n=140) | Cycle 7 (n=103) | Change at Cycle 7 (n=99) | Cycle 25 (n=68) | Change at Cycle 25 (n=67) | Cycle 43 (n=36) | Change at Cycle 43 (n=36) | Cycle 61 (n=22) | Change at Cycle 61 (n=22) | EOT (n=79) | Change at EOT (n=77) |
|---|
| Bevacizumab + Interferon | 71.2 | 71.8 | -1.8 | 72.4 | -2.3 | 71.3 | -0.9 | 70.5 | -1.7 | 65.2 | -7.7 |
Progression-Free Survival (PFS) - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months
PFS at 12 and 24 months is an estimate of the percentages of participants expected to be progression free at 12 and 24 months based on Kaplan-Meier survival analysis of the PFS data. PFS was defined as the time period from the first postbaseline tumor assessment to evidence of disease progression or death from any cause, whichever occurred first. Disease progression included evaluation solely due to symptomatic deterioration or death due to any reason. Censoring at start of any subsequent antineoplastic therapy was not performed. (NCT00796757)
Timeframe: 12 and 24 months
| Intervention | percentage of participants (Number) |
|---|
| 12 months | 24 months |
|---|
| Bevacizumab + Interferon | 58.2 | 28.9 |
Percentage of Participants With Any Health Problems as Assessed by the European Quality of Life 5 Dimensions (EQ-5D) by Visit
EQ-5D is a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point visual analog scale (0=worst, 100=best). Answers from the questionnaire for each dimension (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression) was classified into one of 2 categories: 'no problems' or 'any problems', and the percentage of participants in each category was determined. (NCT00796757)
Timeframe: Screening/Baseline, Cycle 7, Cycle 25, Cycle 43, Cycle 61, and End of Treatment (EOT)
| Intervention | percentage of participants (Number) |
|---|
| Mobility, no problems, Baseline (n=142) | Mobility, any problems, Baseline (n=142) | Mobility, no problems, Cycle 7 (n=106) | Mobility, any problems, Cycle 7 (n=106) | Mobility, no problems, Cycle 25 (n=69) | Mobility, any problems, Cycle 25 (n=69) | Mobility, no problems, Cycle 43 (n=36) | Mobility, any problems, Cycle 43 (n=36) | Mobility, no problems, Cycle 61 (n=22) | Mobility, any problems, Cycle 61 (n=22) | Mobility, no problems, EOT (n=82) | Mobility, any problems, EOT (n=82) | Self-care, no problems, Baseline (n=145) | Self-care, any problems, Baseline (n=145) | Self-care, no problems, Cycle 7 (n=106) | Self-care, any problems, Cycle 7 (n=106) | Self-care, no problems, Cycle 25 (n=69) | Self-care, any problems, Cycle 25 (n=69) | Self-care, no problems, Cycle 43 (n=36) | Self-care, any problems, Cycle 43 (n=36) | Self-care, no problems, Cycle 61 (n=22) | Self-care, any problems, Cycle 61 (n=22) | Self-care, no problems, EOT (n=80) | Self-care, any problems, EOT (n=80) | Usual activity, no problems, Baseline (n=145) | Usual activity, any problems, Baseline (n=145) | Usual activity, no problems, Cycle 7 (n=106) | Usual activity, any problems, Cycle 7 (n=106) | Usual activity, no problems, Cycle 25 (n=69) | Usual activity, any problems, Cycle 25 (n=69) | Usual activity, no problems, Cycle 43 (n=36) | Usual activity, any problems, Cycle 43 (n=36) | Usual activity, no problems, Cycle 61 (n=22) | Usual activity, any problems, Cycle 61 (n=22) | Usual activity, no problems, EOT (n=78) | Usual activity, any problems, EOT (n=78) | Pain/discomfort, no problems, Baseline (n=145) | Pain/discomfort, any problems, Baseline (n=145) | Pain/discomfort, no problems, Cycle 7 (n=106) | Pain/discomfort, any problems, Cycle 7 (n=106) | Pain/discomfort, no problems, Cycle 25 (n=69) | Pain/discomfort, any problems, Cycle 25 (n=69) | Pain/discomfort, no problems, Cycle 43 (n=36) | Pain/discomfort, any problems, Cycle 43 (n=36) | Pain/discomfort, no problems, Cycle 61 (n=22) | Pain/discomfort, any problems, Cycle 61 (n=22) | Pain/discomfort, no problems, EOT (n=80) | Pain/discomfort, any problems, EOT (n=80) | Anxiety/depression, no problems, Baseline (n=144) | Anxiety/depression, any problems, Baseline (n=144) | Anxiety/depression, no problems, Cycle 7 (n=106) | Anxiety/depression, any problems, Cycle 7 (n=106) | Anxiety/depression, no problems, Cycle 25 (n=69) | Anxiety/depression, any problems, Cycle 25 (n=69) | Anxiety/depression, no problems, Cycle 43 (n=36) | Anxiety/depression, any problems, Cycle 43 (n=36) | Anxiety/depression, no problems, Cycle 61 (n=22) | Anxiety/depression, any problems, Cycle 61 (n=22) | Anxiety/depression, no problems, EOT (n=80) | Anxiety/depression, any problems, EOT (n=80) |
|---|
| Bevacizumab + Interferon | 69.0 | 31.0 | 64.2 | 35.8 | 58.0 | 42.0 | 38.9 | 61.1 | 40.9 | 59.1 | 41.3 | 58.8 | 82.8 | 17.2 | 81.1 | 18.9 | 81.2 | 18.8 | 69.4 | 30.6 | 77.3 | 22.7 | 63.8 | 36.3 | 60.7 | 39.3 | 53.8 | 46.2 | 46.4 | 53.6 | 33.3 | 66.7 | 45.5 | 54.5 | 33.3 | 66.7 | 48.3 | 51.7 | 49.1 | 50.9 | 53.6 | 46.4 | 50.0 | 50.0 | 50.0 | 50.0 | 33.8 | 66.3 | 45.8 | 54.2 | 55.7 | 44.3 | 62.3 | 37.7 | 61.1 | 38.9 | 59.1 | 40.9 | 45.0 | 55.0 |
Overall Survival (OS) - Percentage of Participants Estimated to be Alive at 12 and 24 Months
OS at 12 and 24 months is the estimate of the percentages of participants expected to alive at 12 and 24 months based on Kaplan-Meier survival analysis of the survival data. Median OS was defined as the time period from the first bevacizumab infusion to death from any cause. Censoring at start of any subsequent antineoplastic therapy was not performed. (NCT00796757)
Timeframe: Day 0, every 2 weeks until disease progression or end of treatment visit (28 days after last bevacizumab infusion, every 3 months during follow-up, or a maximum of 2 years from enrollment of last participant
| Intervention | percentage of participants (Number) |
|---|
| 12 months | 24 months |
|---|
| Bevacizumab + Interferon | 84.1 | 59.6 |
PFS - Time to Event
PFS was defined as the time period from the first postbaseline assessment tumor assessment to evidence of disease progression or death from any cause, whichever occurred first. Disease progression included evaluation solely due to symptomatic deterioration or death due to any reason. Censoring at start of any subsequent antineoplastic therapy was not performed. (NCT00796757)
Timeframe: Baseline, every 8 weeks to Week 32 then every 12 weeks to disease progression or a maximum of 2 years from enrollment of last participant
| Intervention | months (Median) |
|---|
| Bevacizumab + Interferon | 15.3 |
PFS - Percentage of Participants With an Event
PFS was defined as the time period from the first postbaseline assessment tumor assessment to evidence of disease progression or death from any cause, whichever occurred first. Disease progression included evaluation solely due to symptomatic deterioration or death due to any reason. Censoring at start of any subsequent antineoplastic therapy was not performed. (NCT00796757)
Timeframe: Baseline, every 8 weeks to Week 32 then every 12 weeks to disease progression or a maximum of 2 years from enrollment of last participant
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab + Interferon | 69.2 |
Percentage of Participants Who Experienced at Least 1 Adverse Event.
An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. (NCT00800735)
Timeframe: Baseline through 24 weeks after the end of treatment (up to 72 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Pegylated-interferon Alfa-2a Plus Ribavirin | 80.0 |
Cerebral MRI Assessment: Total Volume of Gd-enhancing T1-lesions Per Scan
Total volume of Gd-enhancing T1-lesions per scan is obtained from the sum of the volumes of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study. (NCT00811395)
Timeframe: 48 weeks
| Intervention | mililiters per scan (Number) |
|---|
| Placebo + IFN-β | 0.068 |
| Teriflunomide 7 mg + IFN-β | 0.019 |
| Teriflunomide 14 mg + IFN-β | 0.020 |
| Placebo + GA | 0.052 |
| Teriflunomide 7 mg + GA | 0.031 |
| Teriflunomide 14 mg + GA | 0.014 |
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA]
"PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review.~Hepatic parameters thresholds were defined as follows:~Alanine Aminotransferase [ALT] >3, 5, 10 or 20 Upper Normal Limit [ULN];~Aspartate aminotransferase [AST] >3, 5, 10 or 20 ULN;~Alkaline Phosphatase >1.5 ULN;~Total Bilirubin [TB] >1.5 or 2 ULN;~ALT >3 ULN and TB >2 ULN;" (NCT00811395)
Timeframe: from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)
| Intervention | participants (Number) |
|---|
| ALT >3 ULN | - ALT >5 ULN | - ALT >10 ULN | AST >3 ULN | - AST >5 ULN | Alkaline Phosphatase >1.5 ULN | TB >1.5 ULN | ALT >3 ULN and TB >2 ULN |
|---|
| Placebo + GA | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
,| Placebo + IFN-β | 2 | 1 | 0 | 1 | 1 | 1 | 0 | 0 |
,| Teriflunomide 14 mg + GA | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Teriflunomide 14 mg + IFN-β | 3 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
,| Teriflunomide 7 mg + GA | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Teriflunomide 7 mg + IFN-β | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Overview of 12-week Sustained Disability Progression
"12-week sustained disability progression was defined as an increase from baseline of at least 1-point in EDSS score (at least 0.5-point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks.~If no disability progression was observed on or before last EDSS evaluation before study drug discontinuation, then the participant was considered as free of disability progression." (NCT00811395)
Timeframe: 48 weeks
| Intervention | participants (Number) |
|---|
| Disability progression | Free of disability progression |
|---|
| Placebo + GA | 4 | 37 |
,| Placebo + IFN-β | 0 | 40 |
,| Teriflunomide 14 mg + GA | 4 | 36 |
,| Teriflunomide 14 mg + IFN-β | 2 | 36 |
,| Teriflunomide 7 mg + GA | 1 | 41 |
,| Teriflunomide 7 mg + IFN-β | 3 | 33 |
Overview of Adverse Events [AE]
AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. (NCT00811395)
Timeframe: from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)
| Intervention | participants (Number) |
|---|
| Any AE | - serious AE | - AE leading to death | - AE leading to study drug discontinuation |
|---|
| Placebo + GA | 39 | 6 | 0 | 2 |
,| Placebo + IFN-β | 35 | 2 | 0 | 2 |
,| Teriflunomide 14 mg + GA | 38 | 2 | 0 | 5 |
,| Teriflunomide 14 mg + IFN-β | 33 | 1 | 0 | 3 |
,| Teriflunomide 7 mg + GA | 40 | 5 | 0 | 3 |
,| Teriflunomide 7 mg + IFN-β | 35 | 4 | 0 | 3 |
Overview of AE With Potential Risk of Occurence
"AE with potential risk of occurrence were defined as follows:~Hepatic disorders;~Immune effects, mainly effects on bone marrow and infection;~Pancreatic disorders;~Malignancy;~Skin disorders, mainly hair loss and hair thinning;~Pulmonary disorders;~Hypertension;~Peripheral neuropathy;~Psychiatric disorders;~Hypersensitivity." (NCT00811395)
Timeframe: from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)
| Intervention | participants (Number) |
|---|
| Any AE with potential risk of occurence | - Hepatic disorder AE | - Immune effects related AE | - Pancreatic disorder AE | - Malignancy AE | - Hair loss / hair thinning AE | - Pulmonary disorder AE | - Hypertension-related AE | - Peripheral neuropathy AE | - Psychiatric disorder AE | - Hypersensitivity AE |
|---|
| Placebo + GA | 34 | 5 | 27 | 6 | 0 | 1 | 0 | 0 | 4 | 3 | 4 |
,| Placebo + IFN-β | 28 | 7 | 16 | 8 | 0 | 1 | 0 | 1 | 5 | 1 | 6 |
,| Teriflunomide 14 mg + GA | 32 | 5 | 21 | 11 | 0 | 7 | 0 | 2 | 10 | 1 | 10 |
,| Teriflunomide 14 mg + IFN-β | 30 | 13 | 20 | 11 | 0 | 4 | 0 | 6 | 4 | 2 | 4 |
,| Teriflunomide 7 mg + GA | 33 | 4 | 22 | 6 | 0 | 5 | 1 | 2 | 5 | 3 | 6 |
,| Teriflunomide 7 mg + IFN-β | 30 | 11 | 21 | 5 | 0 | 3 | 0 | 4 | 3 | 1 | 4 |
Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints
"Probability of disability progression at 24 and 48 weeks was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase. Participants free of disability progression were censored at the date of the last on-treatment EDSS evaluation.~Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t." (NCT00811395)
Timeframe: 48 weeks
| Intervention | percent probability (Number) |
|---|
| Probability of disability progression at 24 weeks | Probability of disability progression at 48 weeks |
|---|
| Placebo + GA | 2.5 | 10.6 |
,| Placebo + IFN-β | 0.0 | 0.0 |
,| Teriflunomide 14 mg + GA | 5.6 | 12.8 |
,| Teriflunomide 14 mg + IFN-β | 2.7 | 6.4 |
,| Teriflunomide 7 mg + GA | 0.0 | 3.3 |
,| Teriflunomide 7 mg + IFN-β | 3.0 | 11.1 |
Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)
"Number of Gd-enhancing T1-lesions per scan is obtained from the total number of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study.~To account for the different number of scans among participants, two Poisson regression models with robust error variance were used (total number of Gd-enhancing T1-lesions as response variable, log-transformed number of scans as offset variable and:~Model 1 (IFN-β groups): Treatment group, region of enrollment, IFN-β dose level and baseline number of Gd-enhancing T1-lesions as covariates~Model 2 (GA groups): Treatment group, region of enrollment and baseline number of Gd-enhancing T1-lesions as covariates)" (NCT00811395)
Timeframe: 48 weeks
| Intervention | lesions per scan (Number) |
|---|
| Placebo + IFN-β | 0.521 |
| Teriflunomide 7 mg + IFN-β | 0.080 |
| Teriflunomide 14 mg + IFN-β | 0.090 |
| Placebo + GA | 0.333 |
| Teriflunomide 7 mg + GA | 0.120 |
| Teriflunomide 14 mg + GA | 0.178 |
Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)
"Total lesion volume is the sum of the total volume of all T2-lesions and the total volume all T1-hypointense post-gadolinium lesions measured through T2/proton density scan analysis and gadolinium-enhanced T1 scan analysis.~Least-square means were estimated using two Mixed-effect models with repeated measures [MMRM] on cubic root transformed volume data:~Model 1 (IFN-β groups): treatment group, region of enrollment, IFN-β dose level, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors;~Model 2 (GA groups): treatment group, region of enrollment, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors." (NCT00811395)
Timeframe: baseline (before randomization in PDY6045 or PDY6046) and 48 weeks
| Intervention | mililiters (mL) (Least Squares Mean) |
|---|
| Placebo + IFN-β | -0.017 |
| Teriflunomide 7 mg + IFN-β | -0.011 |
| Teriflunomide 14 mg + IFN-β | -0.012 |
| Placebo + GA | 0.016 |
| Teriflunomide 7 mg + GA | -0.010 |
| Teriflunomide 14 mg + GA | -0.063 |
Annualized Relapse Rate [ARR]: Poisson Regression Estimates
"ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations.~Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale [EDSS] score or Functional System scores.~To account for the different treatment durations among participants, two Poisson regression models with robust error variance were used (total number of confirmed relapses as response variable, log-transformed treatment duration as offset variable and:~Model 1 (IFN-β groups): treatment group, region of enrollment and IFN-β dose level as covariates~Model 2 (GA groups): treatment group and region of enrollment as covariates)" (NCT00811395)
Timeframe: 48 weeks
| Intervention | relapses per year (Number) |
|---|
| Placebo + IFN-β | 0.343 |
| Teriflunomide 7 mg + IFN-β | 0.231 |
| Teriflunomide 14 mg + IFN-β | 0.144 |
| Placebo + GA | 0.420 |
| Teriflunomide 7 mg + GA | 0.262 |
| Teriflunomide 14 mg + GA | 0.497 |
Percentage of Participants Who Indicated No Difficulty With the Injection Procedure of the Manual Injection or the Avonex Single-use Autoinjector
"Participants assessed whether they had experienced any difficulty with the procedure in preparing, injecting, removing, and disposing process after each injection with the Avonex single-use autoinjector by answering yes or no to the following question: Did you have any difficulty with your injection? The percentage of participants answering no to this question for both the manual injection on Day 1 and the autoinjector on Days 8. 15 and 22 are presented." (NCT00828204)
Timeframe: Day 1, Day 8, Day 15, Day 22
| Intervention | percentage of participants (Number) |
|---|
| Day 1 (Manual Injection); n=70 | Day 8 (Autoinjector); n=71 | Day 15 (Autoinjector); n=71 | Day 22 (Autoinjector); n=71 |
|---|
| Avonex Single-Use Autoinjector: Main Subset | 89 | 90 | 90 | 90 |
Percentage of Participants Who Rated the Avonex Single-use Autoinjector Printed and DVD Training Materials as Very Effective
Participants evaluated how effective the printed and DVD instructions were in educating how to use the Avonex single-use autoinjector. Participants could choose one of the following descriptive answers: not effective at all, somewhat ineffective, neutral, somewhat effective, or very effective. (NCT00828204)
Timeframe: Day 8, Day 15, Day 22
| Intervention | percentage of participants (Number) |
|---|
| Printed instructions, Day 8; n=68 | DVD, Day 8; n=69 | Printed instructions, Day 15; n=42 | DVD, Day 15; n=10 | Printed instructions, Day 22; n=24 | DVD, Day 22; n=9 |
|---|
| Avonex Single-Use Autoinjector: Main Subset | 93 | 88 | 90 | 90 | 92 | 89 |
Mean Score for Ease of Use Grading Scale
Participants scored the ease of use of the Avonex manual injector (Day 1) and single-use autoinjector (Days 8, 15, 22) using a scale that ranged from 0 (extremely difficult) to 10 (extremely easy). (NCT00828204)
Timeframe: Day 1, Day 8, Day 15, Day 22
| Intervention | scores on a scale (Mean) |
|---|
| Day 1 (Manual Injection) n=72, 19 | Day 8 (Autoinjector) n= 72, 18 | Day 15 (Autoinjector) n=71, 16 | Day 22 (Autoinjector) n=70, 7 |
|---|
| Avonex Single-Use Autoinjector: Initial Subset | 7.4 | 6.8 | 6.7 | 5.9 |
,| Avonex Single-Use Autoinjector: Main Subset | 8.1 | 8.9 | 8.7 | 9.3 |
Mean Pain Score After Injection
Participants scored their pain level after the use of the manual prefilled syringe on Day 1 and the Avonex single-use autoinjector on Days 8, 15, and 22 on a scale ranging from 0 (no pain) to 10 (extremely painful). (NCT00828204)
Timeframe: Day 1, Day 8, Day 15, Day 22
| Intervention | scores on a scale (Mean) |
|---|
| Day 1 (Manual Injection) n=72, 19 | Day 8 (Autoinjector) n= 72, 18 | Day 15 (Autoinjector) n=71, 16 | Day 22 (Autoinjector) n=70, 7 |
|---|
| Avonex Single-Use Autoinjector: Initial Subset | 2.5 | 1.9 | 2.1 | 2.4 |
,| Avonex Single-Use Autoinjector: Main Subset | 1.7 | 1.0 | 1.3 | 0.7 |
Percentage of Participants Who Indicated a Preference for the Avonex Single-use Autoinjector Over the Manual Avonex Prefilled Syringe
Participants were asked whether they preferred using the Avonex single-use autoinjector over the manual Avonex prefilled syringe. Preference was defined as participants answering yes to the following question: Do you prefer this single-use autoinjector over the manual injection? (NCT00828204)
Timeframe: Day 23
| Intervention | percentage of participants (Number) |
|---|
| Avonex Single-Use Autoinjector: Main Subset | 94 |
| Avonex Single-Use Autoinjector: Initial Subset | 53 |
Percentage of Participants in the Main Subset With Overall Success Using the Avonex Single-Use Autoinjector
A trainer/observer documented the participant's ability to self-inject with the Avonex single-use autoinjector and completed an observation form. Overall success in using the device for each participant was defined as no failures occurring in any step (ie, device set-up, self-administration of injection, and capping/disposal of the device) during the participant's use of the single-use Avonex autoinjector. (NCT00828204)
Timeframe: Day 22
| Intervention | percentage of participants (Number) |
|---|
| Avonex Single-Use Autoinjector: Main Subset | 89 |
Number of Participants in the Initial Subset Who Were Satisfied With the Avonex Single-Use Autoinjector
"Number of participants in the Initial Subset who answered yes to the question Were you satisfied with this single-use injector? on the Subject Satisfaction Questionnaire." (NCT00828204)
Timeframe: Day 23
| Intervention | participants (Number) |
|---|
| Avonex Single-Use Autoinjector: Initial Subset | 14 |
Mean Score for Initial Subset on Autoinjector Instructions Grading Scale
"Participants in the Initial Subset were asked to answer the question How satisfied are you with the presentation of the autoinjector instructions? on a rating scale of 0 (extremely dissatisfied) to 10 (extremely satisfied)." (NCT00828204)
Timeframe: Day 8
| Intervention | scores on a scale (Mean) |
|---|
| Avonex Single-Use Autoinjector: Initial Subset | 9.5 |
Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector
The clinician/investigator evaluated the injection site for erythema, induration, and tenderness as none, mild, moderate, or severe after the use of the Avonex single-use autoinjector. Temperature at the injection site was evaluated as normal, warm, or hot. Those participants having no erythema, induration, or tenderness, and normal temperature at the injection site after injection are presented. (NCT00828204)
Timeframe: Day 1, Day 8 through 22 (highest severity reported between Days 8 and 22)
| Intervention | percentage of participants (Number) |
|---|
| No Erythema | No Induration | No Tenderness | Normal Temperature |
|---|
| Avonex Single-Use Autoinjector: Initial Subset | 95 | 100 | 79 | 100 |
,| Avonex Single-Use Autoinjector: Main Subset | 65 | 86 | 90 | 100 |
Sustained Virologic Response (SVR)
Proportion of subjects achieving a sustained virologic response (SVR), defined as undetectable HCV RNA 24-weeks after completion of treatment (NCT00845676)
Timeframe: 24 weeks
| Intervention | percentage of participants (Number) |
|---|
| Experimental: Pegylated Interferon Alfa-2a + Ribavirin | 62 |
At Least 50% Shrinkage in Tumor Measurements by Physical Examination
(NCT00846430)
Timeframe: Monthly physical exam first three months and then every three months after, for up to 36 months
| Intervention | Participants (Count of Participants) |
|---|
| Open-Label Intervention | 7 |
No Reported Psychological Toxicity Based Upon Psychological Evaluations
Psychological toxicity defined as suicidal ideation (NCT00846430)
Timeframe: Psychological evaluation at 24 months
| Intervention | Participants (Count of Participants) |
|---|
| Open-Label Intervention | 8 |
Response by MRI Measurements
partial response by RICST criteria is defined as >50% tumor shrinkage (NCT00846430)
Timeframe: evaluated 6, 12 and 24 months compared to baseline
| Intervention | participants (Number) |
|---|
| Partial Response at 6 months | Complete Response at 6 months | Less than Partial Response at 6 months | Partial Response at 12 months | Complete Response at 12 months | Less than Partial Response at 12 months | Partial Response at 24 months | Complete Response at 24 months | Less than Partial Response at 24 months | no longer participating at 24 months |
|---|
| Open-Label Intervention | 0 | 1 | 8 | 2 | 1 | 6 | 4 | 1 | 1 | 3 |
Improvement of Symptoms and Pain
Subjects will be evaluated for pain and Quality of Life scores (NCT00846430)
Timeframe: Monthly physical exam first three months and then every three months after, for up to 36 months
| Intervention | Participants (Count of Participants) |
|---|
| Open-Label Intervention | 9 |
Percentage of Participants With at Least a 2 log10 Maximal Decrease in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Treatment
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1. Data are reported as the percentage of participants. (NCT00851890)
Timeframe: Prior to the first dose on Day 1 and Day 28
| Intervention | percentage of participants (Number) |
|---|
| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | 87.5 |
| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | 87.5 |
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | 62.5 |
| Placebo + pegIFN/RBV | 16.7 |
Number of Participants Having Treatment-emergent Adverse Events (AEs)
"An AE was any untoward medical occurrence that did not have a causal relationship with treatment. An Adverse Drug Reaction (ADR) was any noxious and undesired reaction related to the experimental drug or experiment. A serious adverse event (SAE) was an AE that resulted in death, was life-threatening, resulted in or prolonged hospitalization, resulted in congenital anomaly, was persistent or caused significant disability/incapacity, spontaneous or elective abortion, or required intervention to prevent a serious outcome. AEs were rated for severity as either:~Mild - transient and easily tolerated;~Moderate - caused discomfort and interrupted usual activities;~Severe - caused considerable interference with usual activities, may be incapacitating or life-threatening.~AEs related to direct-acting antiviral agents (DAAs) were assessed as being either probably or possibly related by the investigator." (NCT00851890)
Timeframe: AEs were collected from the time of study drug administration to 30 days after last dose of study drug (8 Weeks)
| Intervention | participants (Number) |
|---|
| Any AE | Any AE at least possibly drug related | Any severe AE | Any serious AE | Any AE leading to discontinuation of study drug | Any fatal events | Deaths |
|---|
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | 8 | 2 | 0 | 0 | 0 | 0 | 0 |
,| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | 8 | 4 | 1 | 0 | 0 | 0 | 0 |
,| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | 8 | 3 | 0 | 0 | 0 | 0 | 0 |
,| Placebo + pegIFN/RBV | 5 | 1 | 0 | 0 | 0 | 0 | 0 |
Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Monotherapy Treatment
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (reported as log10 IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1. The maximal change during monotherapy was nadir minus the baseline log10 HCV RNA level. Nadir was defined as the lowest log10 HCV RNA level any time after the first dose of study drug on Day 1 through the last log10 HCV RNA level before the first dose of study drug on Day 3. Data are reported as the least squares mean change from nadir ± standard error. (NCT00851890)
Timeframe: Prior to the first dose on Day 1 to before first dose on Day 3
| Intervention | log10 IU/mL (Least Squares Mean) |
|---|
| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | -1.01 |
| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | -0.78 |
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | -0.68 |
| Placebo + pegIFN/RBV | -0.26 |
Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (reported as log10 IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1. The maximal change during treatment was nadir minus the baseline log10 HCV RNA level. Nadir was defined as the lowest log10 HCV RNA level any time after the first dose of study drug on Day 1 through the last log10 HCV RNA level on Day 28. Data are reported as the least squares mean change from nadir ± standard error. (NCT00851890)
Timeframe: Prior to the first dose on Day 1 through Day 28
| Intervention | log10 IU/mL (Least Squares Mean) |
|---|
| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | -3.65 |
| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | -3.96 |
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | -3.59 |
| Placebo + pegIFN/RBV | -1.37 |
Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC12) of ABT-333
Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng*hr/mL) measures the total exposure of a drug in blood plasma. The AUC12 of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. (NCT00851890)
Timeframe: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2
| Intervention | ng*hr/mL (Mean) |
|---|
| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | 5852 |
| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | 7548 |
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | 12411 |
Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 25 IU/mL (the Lower Limit of Quantitation [LLOQ]) at Day 28 or Final Visit
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The lower limit of quantification (LLOQ) was defined as HCV RNA levels ≤ 25 IU/mL. Data are reported as the percentage of participants. (NCT00851890)
Timeframe: Day 28 or Final Visit
| Intervention | percentage of participants (Number) |
|---|
| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | 37.5 |
| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | 25.0 |
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | 62.5 |
| Placebo + pegIFN/RBV | 0.00 |
Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28 or Final Visit
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (reported as log10 IU/mL) were determined using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1 and the Day 28 or Final Visit value was the last HCV RNA measurement during the study. Data are reported as the least squares mean change from baseline ± standard error. (NCT00851890)
Timeframe: Day 28 and Final Visit
| Intervention | log10 IU/mL (Least Squares Mean) |
|---|
| Day 28 (n=8, 7, 7, 5) | Final Visit |
|---|
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | -3.24 | -3.48 |
,| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | -3.65 | -3.65 |
,| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | -3.67 | -3.86 |
,| Placebo + pegIFN/RBV | -1.45 | -1.35 |
Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28
Samples from Days 1, 5, 10, 17, 24 and 28 were analyzed for the presence of resistance-associated amino acids using population sequencing and compared to the baseline non-structural viral protein 5B (NS5B) sequence to assess amino acid changes. The amino acid sequence of NS5B before the first dose of ABT-333 on Day 1 was defined as the baseline sequence. The number of participants with variants at resistance-associated amino acid positions in the post-baseline samples are presented. (NCT00851890)
Timeframe: Days 1, 5, 10, 17, 24 and 28
| Intervention | participants (Number) |
|---|
| Day 1 | Day 5 (n=6, 8, 7) | Day 10 (n=6, 6, 7) | Day 17 (n=5, 5, 6) | Day 24 (n=3, 3, 2) | Day 28 (n=4, 3, 3) |
|---|
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | 0 | 1 | 2 | 2 | 1 | 3 |
,| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | 0 | 1 | 1 | 2 | 3 | 2 |
,| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | 1 | 1 | 1 | 2 | 3 | 2 |
Serum Concentrations of Pegylated Interferon (pegIFN)
Blood samples were collected prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28. The samples were analyzed for the concentration of pegIFN (measured in ng/mL) using validated analytical methods and estimated using non-compartmental methods. Data are reported as the mean ± standard deviation. (NCT00851890)
Timeframe: Prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28
| Intervention | ng/mL (Mean) |
|---|
| Prior to morning dose on Day 3 | 4 hours after morning dose on Day 3 (n=7, 8, 8, 6) | Day 4 (n=8, 8, 7, 6) | Day 5 | Day 10 | Day 17 (n=8, 8, 8, 5) | Day 24 (n=8, 7, 8, 5) | Day 28 (n=8, 7, 8, 5) |
|---|
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | 0.00 | 0.09 | 4.95 | 5.57 | 4.72 | 8.73 | 12.1 | 17.0 |
,| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | 0.00 | 0.70 | 6.96 | 9.06 | 7.91 | 12.3 | 12.8 | 17.4 |
,| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | 0.00 | 1.36 | 6.51 | 7.91 | 6.47 | 9.26 | 12.1 | 17.3 |
,| Placebo + pegIFN/RBV | 0.00 | 0.58 | 3.42 | 4.85 | 4.48 | 7.05 | 8.58 | 14.3 |
Time to Maximum Plasma Concentration (Tmax) of ABT-333
Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. (NCT00851890)
Timeframe: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2
| Intervention | Hours (Mean) |
|---|
| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | 3.80 |
| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | 3.50 |
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | 3.50 |
Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 10 IU/mL (Lower Limit of Detection [LLOD]) at Day 28 or Final Visit
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The lower limit of detection (LLOD) was defined as a HCV RNA level equal to 10 IU/mL. Data are reported as the percentage of participants. (NCT00851890)
Timeframe: Day 28 or Final Visit
| Intervention | percentage of participants (Number) |
|---|
| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | 37.5 |
| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | 0.00 |
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | 12.5 |
| Placebo + pegIFN/RBV | 0.00 |
Plasma Concentrations of Ribavirin (RBV)
Blood samples were collected prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28. The samples were analyzed for the concentration of RBV (measured in ng/mL) using validated analytical methods and estimated using non-compartmental methods. Data are reported as the mean ± standard deviation. (NCT00851890)
Timeframe: Prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28
| Intervention | ng/mL (Mean) |
|---|
| Prior to morning dose on Day 3 | 4 hours after morning dose on Day 3 | Day 4 (n=5, 7, 5, 5) | Day 5 (n=6, 6, 8, 5) | Day 10 (n=7, 8, 8, 6) | Day 17 (n=8, 8, 8, 5) | Day 24 (n=8, 7, 8, 5) | Day 28 (n=8, 7, 8, 5) |
|---|
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | 0.00 | 0.51 | 0.29 | 0.48 | 1.02 | 1.32 | 1.60 | 1.56 |
,| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | 0.00 | 0.46 | 0.33 | 0.61 | 1.05 | 1.47 | 1.76 | 1.76 |
,| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | 0.00 | 0.61 | 0.46 | 0.69 | 1.24 | 1.67 | 1.91 | 2.07 |
,| Placebo + pegIFN/RBV | 0.00 | 0.54 | 0.36 | 0.55 | 1.05 | 1.34 | 1.49 | 1.68 |
Maximum Plasma Concentration (Cmax) of ABT-333
Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The Cmax of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. (NCT00851890)
Timeframe: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2
| Intervention | ng/mL (Mean) |
|---|
| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | 883 |
| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | 1236 |
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | 1975 |
Number of Participants With Maximal Phenotypic Resistance to ABT-333 >10 Fold Relative to Baseline Through Day 28
Phenotypic resistance to ABT-333 was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the corresponding baseline sample, and the maximal fold change in EC50 from baseline over the Day 5-28 period. The resistance sample drawn before the first dose of ABT-333 on Day 1 was defined as the baseline sample. The number of participants with phenotypic resistance in the post-baseline samples are presented. (NCT00851890)
Timeframe: Days 1 through 28
| Intervention | participants (Number) |
|---|
| ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV | 4 |
| ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV | 4 |
| ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV | 5 |
Failure-free Survival (FFS)
Failure-free survival is the elapsed time from the date of initiation of study treatment until date of documented disease progression, relapse after response, or death from any cause. For patients alive and free of relapse or progression, follow-up time was censored at the last documented date of failure-free status. (NCT00854581)
Timeframe: From date of treatment initiation until date of documented disease progression, relapse after response, or death from any cause, assessed up to 5 years
| Intervention | months (Median) |
|---|
| Induction + Maintenance | 2.7 |
Expressions of c-Rel, IRF-4 and Other Molecular Events in Participants
Expressions of c-Rel, IRF-4 or other molecular events (p53, p16 mutations) including expansion of novel clones obtained at time of relapse will be compared to baseline data using paired t-test. (NCT00854581)
Timeframe: At time of relapse or disease progression, assessed up to 12 months
| Intervention | participants (Number) |
|---|
| Baseline IRF-4 Expression, Positive | Baseline IRF-4 Expression, Negative | IRF-4 Expression at Relapse, Newly Positive | Baseline c-Rel Expression, Faintly Positive | Baseline c-Rel Expression, Positive | Baseline c-Rel Expression, Negative | Baseline p53 Expression, Positive | Baseline p53 Expression, Negative | Baseline p15/16 alterations, homozygous deletion | Baseline p15/16 alterations, heterozygous deletion | Baseline p15/16 alterations, no deletions |
|---|
| Induction + Maintenance | 3 | 9 | 2 | 3 | 2 | 3 | 1 | 5 | 1 | 2 | 2 |
The Effect of Valproic Acid Therapy on Persistence of Clonal Disease in Patients Who Achieve Clinical Remission
Number of participants achieving a molecular remission after starting valproic acid as evidenced by disappearance of T-cell clonality as measured by gene rearrangement studies using multiplex PCR (NCT00854581)
Timeframe: 3, 6 and 12 months.
| Intervention | participants (Number) |
|---|
| 3 months, CR or PR, with molecular remission | 6 months, CR with molecular remission | 9 months, CR with molecular remission | 12 months, CR with molecular remission |
|---|
| Part 2B Maintenance (Up to 12 Months) | 0 | 1 | 1 | 1 |
Presence of Minimal Residual Disease at 3 and 6 Months of Maintained Remission and at 1 Year Post Initiation of Therapy
"Number of participants achieving complete response (CR) with minimal residual disease at 3, 6 and 12 months post-initiation of protocol therapy. Treatment response was assessed according to the International Consensus Review's adult T-cell leukemia/lymphoma (ATLL) consensus report by Tsukasaki et al published in the Journal of Clinical Oncology (JCO) in 2009.~For imaging, Cheson criteria was used to assess response:~Complete response (CR): Disappearance of all clinical, microscopic, and radiographic evidence of disease. All lymph nodes regressed to normal size (≤ 1.5 cm), and previously involved nodes that were 1.1 to 1.5 cm decreased to ≤ 1.0 cm. In addition, abnormally elevated peripheral blood absolute lymphocyte count (ALC) < 4 x 10^9 /L.~Partial response (PR): ≥ 50% reduction in measurable disease and abnormal lymphocyte count in peripheral blood.~CR or PR had to persist for a period of at least 4 weeks." (NCT00854581)
Timeframe: 3, 6 and 12 months.
| Intervention | participants (Number) |
|---|
| 3 months, CR w/minimal residual disease | 6 months, CR w/minimal residual disease | 12 months, CR w/minimal residual disease |
|---|
| Part 2B Maintenance (Up to 12 Months) | 3 | 1 | 0 |
Number of Patients Achieving Clinical Response to Protocol Therapy Who Lack IRF-4 and/or c-Rel Expression.
"Number of patients achieving clinical response (complete response (CR) + partial response (PR)) who lack interferon regulatory factor 4 (IRF-4) or c-Rel biomarker expression. Treatment response was assessed according to the International Consensus Review's adult T-cell leukemia/lymphoma (ATLL) consensus report by Tsukasaki et al published in the Journal of Clinical Oncology (JCO) in 2009.~For imaging, Cheson criteria was used to assess response:~Complete response (CR): Disappearance of all clinical, microscopic, and radiographic evidence of disease. All lymph nodes regressed to normal size (≤ 1.5 cm), and previously involved nodes that were 1.1 to 1.5 cm decreased to ≤ 1.0 cm. In addition, abnormally elevated peripheral blood absolute lymphocyte count (ALC) < 4 x 10^9 /L.~Partial response (PR): ≥ 50% reduction in measurable disease and abnormal lymphocyte count in peripheral blood.~CR or PR had to persist for a period of at least 4 weeks." (NCT00854581)
Timeframe: Up to 12 months post-initiation of protocol therapy
| Intervention | participants (Number) |
|---|
| Participants with tumors lacking IRF-4 | Participants with tumors lacking c-Rel |
|---|
| Induction + Maintenance | 5 | 2 |
Number of Participants Exhibiting NF-kB Inhibition Upon Treatment With AZT in Vivo
Number of patients exhibiting NF-kb inhibition upon treatment with AZT in vivo. Investigation of whether AZT functions as an inhibitor of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) in vivo by analyzing serially collected leukemic samples during the first 48 hours of treatment with AZT only. The investigators will report the number of participants exhibiting NF-kB inhibition upon treatment with AZT in vivo and correlate with response using two-sample t-test. (NCT00854581)
Timeframe: During 48 hours of first AZT therapy
| Intervention | participants (Number) |
|---|
| CR with Decrease in NF-kB Complex (p50 complexes) | CR with no clear effect NF-kB | PR with Decrease in p50, and Increase in p65 |
|---|
| Induction (Up to Day 21) | 1 | 1 | 1 |
Overall Survival
Overall survival (OS) is the elapsed time from the date of initiation of study treatment until date of death from any cause. In the absence of death, the follow-up was censored at date of last contact. (NCT00854581)
Timeframe: From date of treatment initiation until date of death, assessed up to 5 years
| Intervention | months (Median) |
|---|
| Induction + Maintenance | 7.8 |
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. (NCT00880763)
Timeframe: Up to 6 weeks
| Intervention | Participants (Number) |
|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | 0 |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | 0 |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | 0 |
| Placebo + Peg-IFN + Ribavirin | 0 |
Number of Participants Who Experienced at Least One Adverse Event
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. (NCT00880763)
Timeframe: Up to 6 weeks
| Intervention | Participants (Number) |
|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | 23 |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | 22 |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | 23 |
| Placebo + Peg-IFN + Ribavirin | 22 |
Percentage of Participants Achieving a > or = 3-log10 Decrease in HCV RNA From Baseline to Week 4
Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data. (NCT00880763)
Timeframe: Baseline and Week 4
| Intervention | Percentage of participants (Number) |
|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | 100 |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | 100 |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | 100 |
| Placebo + Peg-IFN + Ribavirin | 85 |
Percentage of Participants Achieving a > or = 2-log10 Decrease in HCV RNA From Baseline to Week 4
Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data. (NCT00880763)
Timeframe: Baseline and Week 4
| Intervention | Percentage of participants (Number) |
|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | 100 |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | 100 |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | 100 |
| Placebo + Peg-IFN + Ribavirin | 95 |
Percentage of Participants Achieving Rapid Viral Response
Rapid viral response (RVR) is defined as undetectable hepatitis C virus ribonucleic acid (HCV RNA) at Week 4. Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The limit of quantification was 1.2 log IU/mL (15 IU/mL) and the limit of detection was <1.2 log IU/mL, but with no specific value. The Data-As-Observed (DAO) approach was used to handle missing data. (NCT00880763)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | 86.4 |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | 95.0 |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | 76.2 |
| Placebo + Peg-IFN + Ribavirin | 20.0 |
Change From Baseline in HCV RNA in log10 at Week 4
Change from baseline in HCV RNA at Week 4 was calculated by subtracting Week 4 HCV RNA level from Baseline HCV RNA level. HCV RNA is measured as International Units per milliliter (IU/mL). Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data. (NCT00880763)
Timeframe: Baseline and Week 4
| Intervention | IU/mL in Log10 (Mean) |
|---|
| Baseline | Change from Baseline |
|---|
| Placebo + Peg-IFN + Ribavirin | 6.6 | -4.7 |
,| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | 6.6 | -6.3 |
,| Vaniprevir 200 mg + Peg-IFN + Ribavirin | 6.6 | -6.5 |
,| Vaniprevir 600 mg + Peg-IFN + Ribavirin | 6.6 | -6.6 |
Core Treatment Period: Overview of Failures
"Failure was defined as the first occurence of confirmed relapse or permanent treatment discontinuation (for any cause) which ever came first. If no events occurred, the participant was considered free of failure.~Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale [EDSS] score or Functional System scores." (NCT00883337)
Timeframe: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled
| Intervention | participants (Number) |
|---|
| Failure | Free of failure |
|---|
| IFN-β-1a | 44 | 60 |
,| Teriflunomide 14 mg | 42 | 69 |
,| Teriflunomide 7 mg | 53 | 56 |
Core Treatment Period: Overview of Adverse Events [AE]
AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. (NCT00883337)
Timeframe: from first study drug intake up to 112 days after last intake in the core treatment period or up to first intake in the extension treatment period, whichever occurred first
| Intervention | participants (Number) |
|---|
| Any AE | - Any serious AE | - Any AE leading to death | - Any AE leading to treatment discontinuation |
|---|
| IFN-β-1a | 97 | 7 | 0 | 22 |
,| Teriflunomide 14 mg | 102 | 6 | 0 | 12 |
,| Teriflunomide 7 mg | 103 | 12 | 0 | 9 |
Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score
"FIS is a subject-reported scale that qualifies the impact of fatigue on daily life in patients with MS. It consists of 40 statements that measure fatigue in three areas; physical, cognitive, and social.~FIS total score ranges from 0 (no problem) to 160 (extreme problem).~Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on FIS total score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors)." (NCT00883337)
Timeframe: Baseline (before randomization) and 48 weeks
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Teriflunomide 7 mg | 0.97 |
| Teriflunomide 14 mg | 4.10 |
| IFN-β-1a | 9.10 |
Core Treatment Period: Annualized Relapse Rate [ARR] - Poisson Regression Estimates
"ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations.~To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as offset variable; treatment group, region of enrollment and baseline EDSS stratum as covariates)." (NCT00883337)
Timeframe: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled
| Intervention | relapses per year (Number) |
|---|
| Teriflunomide 7 mg | 0.410 |
| Teriflunomide 14 mg | 0.259 |
| IFN-β-1a | 0.216 |
Extension Treatment Period: Overview of AEs
AEs were any unfavourable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. (NCT00883337)
Timeframe: From first intake of study drug in extension treatment period up to 28 days after the last intake in the extension treatment period
| Intervention | participants (Number) |
|---|
| Any AE | Any serious AE | Any AE leading to death | Any AE leading to treatment discontinuation |
|---|
| IFN-β-1a / 14 mg | 48 | 12 | 0 | 5 |
,| Teriflunomide 14 mg / 14 mg | 76 | 13 | 0 | 6 |
,| Teriflunomide 7 mg / 14 mg | 83 | 9 | 0 | 8 |
Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores
TSQM version 1.4 is an instrument to assess patients' satisfaction with medication. It consists of 13 questions that cover three dimensions (effectiveness, side effects and convenience) plus a global satisfaction question. Four scores ranging from 0 to 100 (extremely satisfied) are obtained. Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on TSQM score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction as factors). (NCT00883337)
Timeframe: 48 weeks
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Effectivness score | Side effects score | Convenience score | Global satisfaction score |
|---|
| IFN-β-1a | 59.30 | 71.38 | 61.90 | 60.98 |
,| Teriflunomide 14 mg | 63.13 | 93.15 | 89.85 | 68.82 |
,| Teriflunomide 7 mg | 67.25 | 95.29 | 88.30 | 68.29 |
Extension Treatment Period: ARR Poisson Regression Estimates
"ARR was obtained from the total number of confirmed relapses that occurred during the treatment period divided by the sum of the standardized treatment durations.To account for the different treatment durations among participants, a Poisson Regression Model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as offset variable; treatment group, region of enrolment and baseline EDSS stratum as covariates)." (NCT00883337)
Timeframe: Extension treatment period (Maximum: 197 weeks)
| Intervention | relapses per year (Number) |
|---|
| Teriflunomide 7 mg / 14 mg | 0.236 |
| Teriflunomide 14 mg / 14 mg | 0.193 |
| IFN-β-1a / 14 mg | 0.252 |
Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints
"Probability of disability progression at 24, 48 and 96 weeks was estimated using Kaplan-Meier method on the time to failure defined as the time from randomization to failure. Participants free of failure were censored at the date of last treatment.~Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t." (NCT00883337)
Timeframe: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled
| Intervention | percent probability (Number) |
|---|
| Probability of failure at 24 weeks | Probability of failure at 48 weeks | Probability of failure at 96 weeks |
|---|
| IFN-β-1a | 29.8 | 36.5 | 44.4 |
,| Teriflunomide 14 mg | 24.3 | 33.3 | 41.1 |
,| Teriflunomide 7 mg | 25.7 | 35.8 | 58.8 |
Incidence/Severity of Viral Respiratory Infections
Number of subjects in each group with a confirmed viral respiratory infection and the proportion of subjects reporting a mild vs. moderate to severe infection (NCT00895947)
Timeframe: 16 weeks
| Intervention | participants (Number) |
|---|
| incidence of viral respiratory infection | moderate/severe viral respiratory infection | moderate/severe influenza infection | moderate/severe non-influenza infection |
|---|
| Interferon-alpha | 20 | 5 | 1 | 4 |
,| Placebo | 23 | 16 | 4 | 11 |
Symptom Incidence/Severity
Number of subjects in each group reporting 13 different cold/flu symptoms assessed weekly (NCT00895947)
Timeframe: 16 weeks
| Intervention | participants (Number) |
|---|
| any cold/flu symptoms | moderate to severe feverishness | moderate to severe head congestion | moderate to severe sore throat |
|---|
| Interferon-alpha | 86 | 12 | 23 | 27 |
,| Placebo | 92 | 24 | 36 | 39 |
Acute Respiratory Illness
"Number of subjects in each group meeting definition of acute respiratory illness (ARI), defined as 2 or more cold/flu symptoms reported in the same week. Further defined as febrile or afebrile depending on whether the subject reported the symptom of feverishness." (NCT00895947)
Timeframe: 16 weeks
| Intervention | participants (Number) |
|---|
| all acute respiratory illness (ARI) | moderate/severe ARI | moderate/severe febrile ARI | moderate/severe afebrile ARI |
|---|
| Interferon-alpha | 83 | 41 | 12 | 35 |
,| Placebo | 86 | 54 | 24 | 31 |
Frequency of Influenza-like Illness
Number of subjects in each group meeting the definition of influenza-like illness during treatment (i.e. those subject reporting one or more moderate to severe cold/flu symptoms during the treatment period). (NCT00895947)
Timeframe: 16 weeks
| Intervention | participants (Number) |
|---|
| Overall | Age 50 and over | Age under 50 | Seasonal flu vaccine, yes | Seasonal flu vaccine, no | Gender, Male | Gender, Female |
|---|
| Interferon-alpha | 54 | 16 | 38 | 16 | 38 | 11 | 43 |
,| Placebo | 62 | 28 | 34 | 36 | 26 | 22 | 40 |
Impact of Cold/Flu Symptoms
Number of subjects in each group reporting that cold/flu symptoms impacted the following 9 measures of daily life: ability to (1) think clearly, (2) sleep well, (3) breathe easily, (4) walk, climb stairs and exercise, (5) perform daily tasks, (6) work outside the home, (7) work inside the home, (8) interact with others, and (9) live personal life. (NCT00895947)
Timeframe: 16 weeks
| Intervention | participants (Number) |
|---|
| think clearly | sleep well | breathe easily | walk, climb stairs and exercise | perform daily activities | work outside the home | work inside the home | interact with others | live personal life |
|---|
| Interferon-alpha | 53 | 54 | 58 | 44 | 46 | 43 | 42 | 41 | 44 |
,| Placebo | 59 | 64 | 61 | 49 | 54 | 51 | 51 | 50 | 51 |
Number of New Or Newly Enlarging T2 Hyperintense Lesions at 1 Year
Number of new or newly enlarging T2 hyperintense lesions on brain magnetic resonance imaging (MRI) scans. Data observed after participants switched to alternative MS medications are excluded. Adjusted mean is based on negative binomial regression, adjusted for baseline number of T2 lesions. (NCT00906399)
Timeframe: 1 Year
| Intervention | lesions (Mean) |
|---|
| Year 1: Placebo | 10.9 |
| Year 1: Peginterferon Beta-1a Q4W | 7.9 |
| Year 1: Peginterferon Beta-1a Q2W | 3.6 |
Proportion of Participants Relapsed at 1 Year
A relapse is defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurologic findings. Only relapses confirmed by INEC were included in the analysis. Estimated proportion of participants relapsed is based on the Kaplan-Meier product limit method. (NCT00906399)
Timeframe: Year 1
| Intervention | proportion of participants (Number) |
|---|
| Year 1: Placebo | 0.291 |
| Year 1: Peginterferon Beta-1a Q4W | 0.222 |
| Year 1: Peginterferon Beta-1a Q2W | 0.187 |
Estimated Proportion of Participants With Sustained Disability Progression at 1 Year
Sustained disability progression is defined as: at least a 1.0 point increase on the EDSS from baseline EDSS ≥ 1.0 that is sustained for 12 weeks, or at least a 1.5 point increase on the EDSS from baseline EDSS = 0 that is sustained for 12 weeks. The EDSS measures the disability status of people with MS on a scale that ranges from 0 to 10. The range of main categories include 0 (normal neurologic examination), to 5 (ambulatory without aid or rest for 200 meters/disability severe enough to impair full daily activities), to 10 (death due to MS). Estimated proportion of participants with progression based on the Kaplan-Meier product limit method. (NCT00906399)
Timeframe: 1 Year
| Intervention | proportion of participants (Number) |
|---|
| Year 1: Placebo | 0.105 |
| Year 1: Peginterferon Beta-1a Q4W | 0.068 |
| Year 1: Peginterferon Beta-1a Q2W | 0.068 |
Annualized Relapse Rate (ARR) at 1 Year
A relapse is defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurologic findings. Only relapses confirmed by an independent neurology evaluation committee (INEC) are included in the analysis. Data after participants switched to alternative multiple sclerosis (MS) medications are excluded. Data were analyzed using negative binomial regression, adjusted for baseline Expanded Disability Status Scale (EDSS) score (< 4 versus ≥ 4), baseline age (< 40 versus ≥ 40 years), and baseline relapse rate (number of relapses in 3 years prior to study entry divided by 3). (NCT00906399)
Timeframe: 1 Year
| Intervention | relapses per person-years (Number) |
|---|
| Year 1: Placebo | 0.397 |
| Year 1: Peginterferon Beta-1a Q4W | 0.288 |
| Year 1: Peginterferon Beta-1a Q2W | 0.256 |
Overall Survival
The survival time for each patient is defined as the time between randomization and death. Patients lost to follow-up or still alive at the date of last evaluation have been censored. (NCT00911443)
Timeframe: 2 years
| Intervention | months (Median) |
|---|
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 1.6 mg | 9.3 |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 3.2 mg | 8.6 |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 6.4 mg | 10.3 |
| Dacarbazin + Thymosin-alpha-1 3.2 mg | 9.3 |
| Dacarbazin + Interferon Alpha | 6.6 |
Overall Tumor Response
Tumor response is measured according to Response Evaluation Criteria In Solid Tumors (RECIST) computing number of Complete Response plus Partial Response (NCT00911443)
Timeframe: 1 year
| Intervention | participants (Number) |
|---|
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 1.6 mg | 7 |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 3.2 mg | 10 |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 6.4 mg | 6 |
| Dacarbazin + Thymosin-alpha-1 3.2 mg | 12 |
| Dacarbazin + Interferon Alpha | 4 |
Progression Free Survival
Progression Free Survival is defined as the time from the randomization to progression or death (NCT00911443)
Timeframe: 2 years
| Intervention | months (Median) |
|---|
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 1.6 mg | 1.9 |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 3.2 mg | 1.8 |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 6.4 mg | 1.8 |
| Dacarbazin + Thymosin-alpha-1 3.2 mg | 2.0 |
| Dacarbazin + Interferon Alpha | 1.8 |
Early Virologic Response (EVR)
(NCT00919633)
Timeframe: Study week 12
| Intervention | participants (Number) |
|---|
| Group 4: Peginterferon Alfa-2b (1.5 μg/kg) | 7 |
| Group 1: Interferon Alfa-2b (Dose 1) | 15 |
| Group 2: Interferon Alfa-2b (Dose 2) | 13 |
| Group 3: Interferon Alfa-2b (Dose 3) | 11 |
Rapid Virologic Response (RVR)
(NCT00919633)
Timeframe: Study Week 4
| Intervention | participants (Number) |
|---|
| Group 4: Peginterferon Alfa-2b (1.5 μg/kg) | 2 |
| Group 1: Interferon Alfa-2b (Dose 1) | 4 |
| Group 2: Interferon Alfa-2b (Dose 2) | 7 |
| Group 3: Interferon Alfa-2b (Dose 3) | 11 |
Viral Load: Incidence of Sustained Virologic Response (SVR)
(NCT00919633)
Timeframe: 24 weeks after treatment is complete
| Intervention | participants (Number) |
|---|
| Group 4: Peginterferon Alfa-2b (1.5 μg/kg) | 4 |
| Group 1: Interferon Alfa-2b (Dose 1) | 7 |
| Group 2: Interferon Alfa-2b (Dose 2) | 2 |
| Group 3: Interferon Alfa-2b (Dose 3) | 4 |
Number of Participants Who Experienced an Adverse Event
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. (NCT00943761)
Timeframe: up to 72 weeks
| Intervention | Participants (Number) |
|---|
| Vaniprevir 300 mg b.i.d. + Peg-IFN + RBV | 21 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN + RBV | 23 |
Number of Participants Who Experienced a Serious Adverse Event
Serious adverse event is defined as any adverse drug or biologic or device experience occurring at any dose resulting in death, was life-threatening, was persistent or caused significant disability/incapacity, required in-patient hospitalization or prolonged hospitalization, was a congenital anomaly or birth defect, was a cancer, or was an overdose. (NCT00943761)
Timeframe: up to 72 weeks
| Intervention | Participants (Number) |
|---|
| Vaniprevir 300 mg b.i.d. + Peg-IFN + RBV | 4 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN + RBV | 1 |
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. (NCT00943761)
Timeframe: 48 weeks
| Intervention | Participants (Number) |
|---|
| Vaniprevir 300 mg b.i.d. + Peg-IFN + RBV | 2 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN + RBV | 1 |
Percentage of Participants Who Achieved Sustained Viral Response 24 Weeks After the End of Treatment (SVR24)
SVR24 is defined as undetectable hepatitis C virus ribonucleic acid (HCV RNA) 24 weeks after the end of vaniprevir study therapy. HCV RNA plasma levels were assessed using the Roche COBAS Taqman assay (or equivalent) with the limit of quantification (LoQ) of at least 25 IU/mL and the limit of detection (LoD) of at least 10 IU/mL. (NCT00943761)
Timeframe: 72 weeks
| Intervention | Percentage of participants (Number) |
|---|
| Vaniprevir 300 mg b.i.d. + Peg-IFN + RBV | 66.7 |
| Vaniprevir 600 mg b.i.d. + Peg-IFN + RBV | 70.6 |
t1/2,ss for BI 201335 ZW
terminal half-life of the analyte in plasma at steady state (t1/2,ss) (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
| Intervention | hour(s) (Geometric Mean) |
|---|
| BI 201335 NA Low TN | 29.3 |
| BI 201335 NA High TN | 21.2 |
| BI 201335 NA High TE | 23.0 |
Tmax for BI 201335 ZW
Time to maximum plasma concentration (tmax) of BI 201335 ZW after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
| Intervention | hour(s) (Median) |
|---|
| BI 201335 NA Low TN | 4.98 |
| BI 201335 NA High TN | 5.50 |
| BI 201335 NA High TE | 7.97 |
Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV
Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in SOC period for treatment naive patients and treatment experienced patients. (NCT00947349)
Timeframe: 44 weeks
| Intervention | participant(s) (Number) |
|---|
| Decrease haematocrit | Decrease haemoglobin | Decrease red blood cell ct. | Decrease white blood cell ct. | Decrease platelets | Increase eosinophils | Decrease sodium | Decrease potassium | Increase bicarbonate | Increase uric acid | Increase triglyceride | Increase U. pH | Increase AST/GOT, SGOT | Increase ALT/GPT, SGPT |
|---|
| SOC TE 240 mg | 4 | 5 | 3 | 3 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 1 |
,| SOC TN 120 mg | 3 | 2 | 3 | 5 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 1 |
,| SOC TN 240 mg | 5 | 2 | 4 | 5 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
,| SOC TN Placebo | 1 | 4 | 0 | 3 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
Tmax for RBV
Time to maximum plasma concentration (tmax) of RBV after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
| Intervention | hour(s) (Median) |
|---|
| Placebo TN | 1.94 |
| BI 201335 NA Low TN | 3.98 |
| BI 201335 NA High TN | 3.92 |
| BI 201335 NA High TE | 4.98 |
Tmax, ss for BI 201335 ZW
Time from last dosing to the maximum plasma concentration (tmax) of BI 201335 ZW after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
| Intervention | hour(s) (Median) |
|---|
| BI 201335 NA Low TN | 3.83 |
| BI 201335 NA High TN | 2.99 |
| BI 201335 NA High TE | 3.49 |
Tmax, ss for RBV
Time to the maximum plasma concentration (tmax) of RBV after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
| Intervention | hour(s) (Median) |
|---|
| Placebo TN | 2.42 |
| BI 201335 NA Low TN | 2.92 |
| BI 201335 NA High TN | 2.90 |
| BI 201335 NA High TE | 3.92 |
Week 2 Virological Response (W2VR)
Number of patients satisfying W2VR (plasma HCV RNA (Hepatitis C Virus Ribonucleic acid) level below the limit of quantification (BLQ)) (NCT00947349)
Timeframe: 2 weeks
| Intervention | participants (Number) |
|---|
| Placebo in TN | 0 |
| BI 201335 NA Low TN | 5 |
| BI 201335 NA High TN | 6 |
| BI 201335 NA High TE | 3 |
Week 4 Virological Response (W4VR)
Number of patients satisfying W4VR (plasma HCV RNA level below the limit of quantification (BLQ)) (NCT00947349)
Timeframe: 4 weeks
| Intervention | participants (Number) |
|---|
| Placebo TN | 0 |
| BI 201335 NA Low TN | 6 |
| BI 201335 NA High TN | 6 |
| BI 201335 NA High TE | 5 |
Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV
An assessment of tolerability for the safety of the SOC with PegIFN alfa-2a and RBV. (NCT00947349)
Timeframe: 44 weeks
| Intervention | participant(s) (Number) |
|---|
| Good | Satisfactory | Not satisfactory | Bad |
|---|
| SOC TE 240 mg | 3 | 1 | 2 | 0 |
,| SOC TN 120 mg | 4 | 0 | 1 | 0 |
,| SOC TN 240 mg | 1 | 2 | 1 | 2 |
,| SOC TN Placebo | 2 | 2 | 0 | 0 |
Assessment of Tolerability in Triple Combination Therapy
An assessment of tolerability for the safety of the triple combination therapy with BI 201335 NA, PegIFN α -2a and RBV. (NCT00947349)
Timeframe: 4 weeks
| Intervention | participants (Number) |
|---|
| Good | Satisfactory | Not Satisfactory | Bad |
|---|
| Triple TE 240 mg | 6 | 0 | 0 | 0 |
,| Triple TN 120 mg | 5 | 1 | 0 | 0 |
,| Triple TN 240 mg | 5 | 1 | 0 | 0 |
,| Triple TN Placebo | 3 | 0 | 1 | 0 |
Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy
Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in triple combination therapy for treatment naive patients and treatment experienced patients. (NCT00947349)
Timeframe: 4 weeks
| Intervention | participants (Number) |
|---|
| Decrease Haematocrit | Decrease Haemoglobin | Decrease Red blood cell ct. | Decrease White blood cell ct. | Decrease Platelets | Increase Eosinophils | Decrease Sodium | Decrease Potassium | Decrease Bicarbonate | Increase Bicarbonate | Increase Bilirubin, total | Increase Bilirubin, direct | Increase Protein, total | Increase Uric acid | Increase Triglyceride | Increase U. pH |
|---|
| Triple TE 240 mg | 4 | 4 | 2 | 4 | 0 | 0 | 1 | 0 | 1 | 2 | 5 | 4 | 0 | 1 | 4 | 0 |
,| Triple TN 120 mg | 2 | 3 | 2 | 4 | 1 | 0 | 2 | 0 | 1 | 2 | 2 | 1 | 0 | 2 | 0 | 1 |
,| Triple TN 240 mg | 3 | 2 | 2 | 5 | 0 | 1 | 2 | 1 | 0 | 1 | 6 | 3 | 1 | 0 | 1 | 0 |
,| Triple TN Placebo | 2 | 3 | 1 | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 |
CL/F,ss for BI 201335 ZW
apparent clearance of the analyte (BI 201335 ZW) in plasma at steady state (CL/F,ss) following multiple oral administration (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
| Intervention | mL/min (Geometric Mean) |
|---|
| BI 201335 NA Low TN | 28.2 |
| BI 201335 NA High TN | 11.1 |
| BI 201335 NA High TE | 8.01 |
AUCτ,1 for BI 201335 ZW
Area under the curve (AUC) concentration after the first dose of BI 201335 ZW (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| BI 201335 NA Low TN | 68900 |
| BI 201335 NA High TN | 171000 |
| BI 201335 NA High TE | 233000 |
AUCτ,1 for Ribavirin (RBV)
Area under the plasma concentration curve of RBV after the first dose of placebo or BI 201335 NA with with RBV and PegIFN alfa-2a (NCT00947349)
Timeframe: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Placebo TN | 5160 |
| BI 201335 NA Low TN | 4660 |
| BI 201335 NA High TN | 4620 |
| BI 201335 NA High TE | 3500 |
AUCτ,ss of BI 201335 ZW
AUC at steady state after 4 weeks combination of the last dose (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| BI 201335 NA Low TN | 70800 |
| BI 201335 NA High TN | 361000 |
| BI 201335 NA High TE | 499000 |
AUCτ,ss of RBV
Area under the plasma concentration curve of RBV after the multiple oral administration of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state (NCT00947349)
Timeframe: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Placebo TN | 27500 |
| BI 201335 NA Low TN | 25200 |
| BI 201335 NA High TN | 22400 |
| BI 201335 NA High TE | 20000 |
Cavg for BI 201335 ZW
average plasma concentration (Cavg) of BI 201335 ZW (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
| Intervention | ng/mL (Geometric Mean) |
|---|
| BI 201335 NA Low TN | 2950 |
| BI 201335 NA High TN | 15000 |
| BI 201335 NA High TE | 20800 |
Cavg for RBV
average plasma concentration (Cavg) of RBV (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
| Intervention | ng/mL (Geometric Mean) |
|---|
| Placebo TN | 2290 |
| BI 201335 NA Low TN | 2100 |
| BI 201335 NA High TN | 1860 |
| BI 201335 NA High TE | 1670 |
Change From Baseline in HCV Viral Load
Change form baseline in HCV viral load (log10) after 4 weeks (NCT00947349)
Timeframe: baseline and week 4
| Intervention | IU/mL (Mean) |
|---|
| Placebo TN | -3.30 |
| BI 201335 NA Low TN | -5.88 |
| BI 201335 NA High TN | -5.95 |
| BI 201335 NA High TE | -5.53 |
Cmax of BI 201335 ZW
Maximum concentration of BI 201335 ZW after multiple oral admin. of BI 201335 NA with RBV and PegIFN alfa-2a (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
| Intervention | ng/mL (Geometric Mean) |
|---|
| BI 201335 NA Low TN | 5500 |
| BI 201335 NA High TN | 12600 |
| BI 201335 NA High TE | 15000 |
Cmax of RBV
Maximum Plasma concentration of RBV after multiple oral admin. of placebo with RBV and PegIFN alfa-2a (NCT00947349)
Timeframe: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose
| Intervention | ng/mL (Geometric Mean) |
|---|
| Placebo TN | 1130 |
| BI 201335 NA Low TN | 761 |
| BI 201335 NA High TN | 724 |
| BI 201335 NA High TE | 509 |
Cmax,ss of BI 201335 ZW
Maximum concentration of BI 201335 ZW at steady state (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
| Intervention | ng/mL (Geometric Mean) |
|---|
| BI 201335 NA Low TN | 5880 |
| BI 201335 NA High TN | 24500 |
| BI 201335 NA High TE | 29100 |
Cmax,ss of RBV
Maximum Plasma concentration of RBV after multiple oral admin. of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state (NCT00947349)
Timeframe: -0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose
| Intervention | ng/mL (Geometric Mean) |
|---|
| Placebo TN | 3060 |
| BI 201335 NA Low TN | 2710 |
| BI 201335 NA High TN | 2280 |
| BI 201335 NA High TE | 2130 |
Cmin,ss for BI 201335 ZW
Minimum concentration of the analyte (BI 201335 ZW) in plasma over the dosing interval at steady state (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
| Intervention | ng/mL (Geometric Mean) |
|---|
| BI 201335 NA Low TN | 1550 |
| BI 201335 NA High TN | 10200 |
| BI 201335 NA High TE | 16000 |
Cmin,ss for RBV
Minimum concentration of the analyte (RBV) in plasma over the dosing interval at steady state (NCT00947349)
Timeframe: 10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
| Intervention | ng/mL (Geometric Mean) |
|---|
| Placebo TN | 1980 |
| BI 201335 NA Low TN | 1730 |
| BI 201335 NA High TN | 1590 |
| BI 201335 NA High TE | 1400 |
Complete Early Virological Response (cEVR)
Number of patients with plasma HCV RNA level BLD at Week 12 (NCT00947349)
Timeframe: 12 weeks
| Intervention | participants (Number) |
|---|
| Placebo TN | 3 |
| BI 201335 NA Low TN | 5 |
| BI 201335 NA High TN | 5 |
| BI 201335 NA High TE | 6 |
Day 28 Virologic Response
Number of patients with HCV viral load reduction >= 2 log10 at Week 4 (NCT00947349)
Timeframe: 4 weeks
| Intervention | participants (Number) |
|---|
| Placebo TN | 3 |
| BI 201335 NA Low TN | 6 |
| BI 201335 NA High TN | 6 |
| BI 201335 NA High TE | 6 |
Early Virological Response (EVR)
Number of patients with reduction >= 2 log10 in plasma HCV RNA level at Week 12 (NCT00947349)
Timeframe: 12 Weeks
| Intervention | participants (Number) |
|---|
| Placebo TN | 4 |
| BI 201335 NA Low TN | 5 |
| BI 201335 NA High TN | 6 |
| BI 201335 NA High TE | 6 |
End of Treatment Response (ETR)
Number of patients with plasma HCV RNA level BLD at week 48 (NCT00947349)
Timeframe: 48 weeks
| Intervention | participants (Number) |
|---|
| Placebo TN | 3 |
| BI 201335 NA Low TN | 5 |
| BI 201335 NA High TN | 4 |
| BI 201335 NA High TE | 4 |
Rapid Virological Response (RVR)
Number of patients satisfying RVR (plasma HCV RNA level below the limit of detection (BLD) at Week 4) (NCT00947349)
Timeframe: 4 weeks
| Intervention | participants (Number) |
|---|
| Placebo TN | 0 |
| BI 201335 NA Low TN | 5 |
| BI 201335 NA High TN | 6 |
| BI 201335 NA High TE | 4 |
Sustained Virologic Response (SVR)
Number of patients with plasma HCV RNA level BLD 24 weeks after treatment completion (NCT00947349)
Timeframe: 72 weeks
| Intervention | participants (Number) |
|---|
| Placebo TN | 2 |
| BI 201335 NA Low TN | 4 |
| BI 201335 NA High TN | 5 |
| BI 201335 NA High TE | 3 |
Percentage of Participants With HCV Virologic Breakthrough or Incomplete Virologic Response/Rebound
Virologic breakthrough is defined as achieving undetectable HCV-RNA and subsequently having an HCV-RNA level of >1000 IU/mL. Incomplete Virologic Response/Rebound is defined as having a one log10 increase in HCV-RNA from the participant's nadir, with an HCV-RNA >1000 IU/mL. HCV-RNA was detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL. (NCT00959699)
Timeframe: Up to Week 72
| Intervention | percentage of participants (Number) |
|---|
| Virologic breakthrough | Incomplete response |
|---|
| PegIFN-2b + RBV | 0 | 17.6 |
,| PegIFN-2b + RBV + Boceprevir | 6.3 | 9.4 |
Change From Baseline in log10 HCV-RNA at Treatment Week 4 (TW4)
This is a measure of the change in the amount of HCV-RNA in the plasma at the end of 4 weeks of treatment. HCV-RNA was detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL. (NCT00959699)
Timeframe: Baseline and Week 4
| Intervention | participants (Number) |
|---|
| Participants with <1 positive log drop | Participants with >= 1 positive log drop | Participants with undetectable HCV-RNA | Participants with missing data |
|---|
| PegIFN-2b + RBV | 15 | 16 | 3 | 0 |
,| PegIFN-2b + RBV + Boceprevir | 28 | 32 | 3 | 1 |
Percentage of Participants Achieving SVR24 Among Randomized Participants Who Received At Least One Dose of Boceprevir (Experimental) or Placebo (Control)
SVR24 is defined as undetectable plasma HCV-RNA 24 weeks after the end of all study treatment. If there was no value in the FW24 visit window, the closest value available chronologically after this window was used; if a value was still missing after that, the value from FW12 was used. HCV-RNA is detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL. (NCT00959699)
Timeframe: Up to Week 72
| Intervention | percentage of participants (Number) |
|---|
| PegIFN-2b + RBV | 30.3 |
| PegIFN-2b + RBV + Boceprevir | 64.5 |
Percentage of Participants Achieving Sustained Viral Response (SVR) at Follow-up Week 24 (FW24) Among Randomized Participants Who Received At Least One Dose of Trial Medication
SVR24 is defined as undetectable plasma hepatitis C virus ribonucleic acid (HCV-RNA) at 24 weeks after the end of all study treatment. If there was no value in the FW24 visit window, the closest value available chronologically after this window was used; if a value was still missing after that, the value from Follow-up Week 12 (FW12) was used. HCV-RNA is detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL. (NCT00959699)
Timeframe: Up to Week 72
| Intervention | percentage of participants (Number) |
|---|
| PegIFN-2b + RBV | 29.4 |
| PegIFN-2b + RBV + Boceprevir | 62.5 |
Percentage of Participants With Early Virologic Response (EVR) Who Achieved SVR24
EVR was defined as undetectable HCV-RNA at Treatment Week (TW) 2, 4, 8, or 12. HCV-RNA was detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL. (NCT00959699)
Timeframe: Up to Week 12
| Intervention | percentage of participants (Number) |
|---|
| HCV-RNA undetectable at Week 2 (n=0, 0) | HCV-RNA undetectable at Week 4 (n=3, 3) | HCV-RNA undetectable at Week 8 (n=5, 27) | HCV-RNA undetectable at Week 12 (n=8, 38) |
|---|
| PegIFN-2b + RBV | 0 | 100 | 100 | 87.5 |
,| PegIFN-2b + RBV + Boceprevir | 0 | 100 | 92.6 | 92.1 |
Percentage of Participants With Undetectable HCV-RNA at Follow-up Week 12 (FW12)
The virologic response at FW12 was considered SVR12 with an additional rule for handling missing data: participants with missing HCV-RNA assessment at FW12 but having non-missing, undetectable HCV-RNA assessments at both FW4 and FW24, were assumed to be responders for SVR12. HCV-RNA was detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL. (NCT00959699)
Timeframe: Up to Week 60
| Intervention | percentage of participants (Number) |
|---|
| PegIFN-2b + RBV | 26.5 |
| PegIFN-2b + RBV + Boceprevir | 62.5 |
Time to Reach a Plasma HCV RNA Level BLD While on Treatment
Time to reach a plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) level below the lower limit of detection (BLD) while on treatment (NCT00984620)
Timeframe: 48 weeks
| Intervention | week (Median) |
|---|
| Faldaprevir 120 mg (12 Weeks) | 4.1 |
| Faldaprevir 120 mg (24 Weeks) | 4.1 |
Laboratory Test Abnormalities and Study Medication Tolerabilities
Participants with possible clinically significant laboratory test abnormalities observed in functional groups: Haematology, Coagulation, Electrolytes, Enzymes, Substrates and Differentials, automatic. (NCT00984620)
Timeframe: 48 weeks
| Intervention | participants (Number) |
|---|
| Red blood cell count: low (N=81, N=79) | haematocrit: low (N=81, N=79) | haematocrit: high(N=81, N=79) | white blood cell count: low(N=81, N=79) | platelets: low(N=81, N=78) | eosinophils: high (N=81, N=79) | PT-INR: high (N=81, N=79) | sodium: low (N=81, N=79) | bicarbonate: low (N=79, N=74) | bicarbonate: high (N=79, N=74) | AST/GOT, SGOT: high (N=75, N=71) | ALT/GPT, SGPT: high (N=68, N=64) | alkaline phosphatase: high (N=80, N=79) | GGT: high (N=74, N=72) | creatine kinase: high (N=80, N=79) | lipase: high (N=79, N=79) | amylase: high (N=81, N=79) | glucose: low (N=80, N=79) | cholesterol, total: high (N=80, N=75) | triglyceride: high (N=74, N=71) |
|---|
| Faldaprevir 120 mg (12 Weeks) | 9 | 30 | 0 | 56 | 5 | 1 | 1 | 1 | 6 | 1 | 3 | 3 | 1 | 4 | 0 | 1 | 1 | 0 | 6 | 13 |
,| Faldaprevir 120 mg (24 Weeks) | 8 | 21 | 1 | 60 | 2 | 5 | 1 | 1 | 11 | 1 | 3 | 5 | 0 | 8 | 3 | 3 | 2 | 2 | 2 | 18 |
Number of Participants With Clinically Relevant Abnormalities Vital Signs, and Physical Examination
No number of participants with clinically relevant abnormalities in vital signs and physical examination. (NCT00984620)
Timeframe: 48 weeks
| Intervention | participants with abnormality (Number) |
|---|
| Faldaprevir 120mg (12 Weeks) | 0 |
| Faldaprevir 120mg (24 Weeks) | 0 |
Viral Load (HCV RNA) at All Visits During Treatment and Follow-up
Viral load of Hepatitis C virus Ribonucleic acid (HCV RNA) at all visits during treatment (TRT) and follow-up, ie. change from baseline viral load at all visits. (NCT00984620)
Timeframe: From baseline to 72 weeks
| Intervention | IU/mL (Mean) |
|---|
| week 2, change from baseline (N=76, N=78) | week 4, change from baseline (N=76, N=77) | week 8, change from baseline (N=75, N=76) | week 12, change from baseline (N=76, N=76) | week 16, change from baseline (N=18, N=13) | week 20, change from baseline (N=52, N=57) | week 24, change from baseline (N=12, N=8) | week 28, change from baseline (N=4, N=4) | week 36, change from baseline (N=4, N=2) | End of TRT, change from baseline (N=80, N=78) | 4 wks after TRT, change from baseline (N=75, N=77) | 12 wks after TRT, change from baseline (N=75,N=75) | 24 wks after TRT, change from baseline (N=73,N=75) |
|---|
| Faldaprevir 120 mg (12 Weeks) | -4.724 | -4.993 | -5.128 | -5.117 | -5.363 | -5.056 | -4.176 | -5.723 | -5.624 | -4.910 | -4.296 | -4.154 | -4.103 |
,| Faldaprevir 120 mg (24 Weeks) | -4.866 | -5.081 | -5.088 | -5.107 | -5.262 | -5.366 | -4.740 | -4.369 | -5.958 | -5.017 | -4.367 | -4.353 | -4.250 |
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (6)
Change from baseline (CFB) in PT-INR (ratio). (NCT00984620)
Timeframe: baseline and 48 weeks
| Intervention | ratio (Mean) |
|---|
| PT-INR (ratio), CFB, Day 1(N=77, N=72) | PT-INR (ratio), CFB, wk2 (N=76, N=78) | PT-INR (ratio), CFB, wk4(N=74, N=76) | PT-INR (ratio), CFB, wk8(N=73, N=75) | PT-INR (ratio), CFB, wk12(N=74, N=72) | PT-INR (ratio), CFB, wk18(N=69, N=70) | PT-INR (ratio), CFB, wk24(N=12, N=4) | PT-INR (ratio), CFB, wk28(N=5, N=3) | PT-INR (ratio), CFB, wk36(N=4, N=2) | PT-INR (ratio), CFB, EoT(N=68, N=73) |
|---|
| Faldaprevir 120mg (12 Weeks) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | -0.1 | 0.0 | 0.0 |
,| Faldaprevir 120mg (24 Weeks) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.1 | 0.0 | -0.1 | 0.0 |
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (5)
Change from baseline (CFB) in AST/GOT, ALT/GPT, Alka. phosphatase, GGT, Creatine kinase, Lipase, and Amylase. (NCT00984620)
Timeframe: baseline and 48 weeks
| Intervention | U/L (Mean) |
|---|
| AST/GOT (U/L), CFB, Day 1(N=74, N=75) | AST/GOT (U/L), CFB, wk2 (N=75, N=78) | AST/GOT (U/L), CFB, wk4 (N=74, N=76) | AST/GOT (U/L), CFB, wk8 (N=74, N=76) | AST/GOT (U/L), CFB, wk12 (N=74, N=76) | AST/GOT (U/L), CFB, wk18 (N=67, N=70) | AST/GOT (U/L), CFB, wk24 (N=12, N=4) | AST/GOT (U/L), CFB, wk28 (N=5, N=3) | AST/GOT (U/L), CFB, wk36 (N=4, N=2) | AST/GOT (U/L), CFB, EoT (N=66, N=71) | ALT/GPT (U/L), CFB, day1 (N=76, N=75) | ALT/GPT (U/L), CFB, wk2 (N=75, N=78) | ALT/GPT (U/L), CFB, wk4 (N=74, N=77) | ALT/GPT (U/L), CFB, wk8 (N=74, N=76) | ALT/GPT (U/L), CFB, wk12 (N=74, N=76) | ALT/GPT (U/L), CFB, wk18 (N=67, N=70) | ALT/GPT (U/L), CFB, wk24 (N=12, N=4) | ALT/GPT (U/L), CFB, wk28 (N=5, N=3) | ALT/GPT (U/L), CFB, wk36 (N=4, N=2) | ALT/GPT (U/L), CFB, EoT (N=66, N=71) | Alka. phosphatase (U/L), CFB, day1 (n=77, N=75) | Alka. phosphatase (U/L), CFB, wk2 (n=76, N=78) | Alka. phosphatase (U/L), CFB, wk4 (n=76, N=77) | Alka. phosphatase (U/L), CFB, wk8 (n=75, N=76) | Alka. phosphatase (U/L), CFB, wk12 (n=75, N=76) | Alka. phosphatase (U/L), CFB, wk18 (n=68, N=70) | Alka. phosphatase (U/L), CFB, wk24 (n=12, N=4) | Alka. phosphatase (U/L), CFB, wk28 (n=5, N=3) | Alka. phosphatase (U/L), CFB, wk36 (n=4, N=2) | Alka. phosphatase (U/L), CFB, EoT (n=67, N=73) | GGT (U/L), CFB, day1 (N=77, N=75) | GGT (U/L), CFB, wk2 (N=76, N=78) | GGT (U/L), CFB, wk4 (N=76, N=77) | GGT (U/L), CFB, wk8 (N=75, N=76) | GGT (U/L), CFB, wk12 (N=75, N=76) | GGT (U/L), CFB, wk18 (N=68, N=70) | GGT (U/L), CFB, wk24 (N=12, N=4) | GGT (U/L), CFB, wk28 (N=5, N=3) | GGT (U/L), CFB, wk36 (N=4, N=2) | GGT (U/L), CFB, EoT (N=67, N=73) | Creatine kinase (U/L), CFB, day1 (N=76, N=75) | Creatine kinase (U/L), CFB, wk2 (N=75, N=78) | Creatine kinase (U/L), CFB, wk4 (N=74, N=77) | Creatine kinase (U/L), CFB, wk8 (N=74, N=76) | Creatine kinase (U/L), CFB, wk12 (N=74, N=75) | Creatine kinase (U/L), CFB, wk18 (N=67, N=70) | Creatine kinase (U/L), CFB, wk24 (N=12, N=4) | Creatine kinase (U/L), CFB, wk28 (N=5, N=3) | Creatine kinase (U/L), CFB, wk36 (N=4, N=2) | Creatine kinase (U/L), CFB, EoT (N=66, N=71) | Lipase (U/L). CFB, day1 (N=77, N=75) | Lipase (U/L). CFB, wk2 (N=76, N=78) | Lipase (U/L). CFB, wk4 (N=76, N=76) | Lipase (U/L). CFB, wk8 (N=75, N=76) | Lipase (U/L). CFB, wk12 (N=75, N=75) | Lipase (U/L). CFB, wk18 (N=68, N=70) | Lipase (U/L). CFB, wk24 (N=12, N=4) | Lipase (U/L). CFB, wk28 (N=5, N=3) | Lipase (U/L). CFB, wk36 (N=4, N=2) | Lipase (U/L). CFB, EoT (N=67, N=73) | Amylase (U/L), CFB, day1 (N=77, N=75) | Amylase (U/L), CFB, wk2 (N=76, N=78) | Amylase (U/L), CFB, wk4 (N=76, N=77) | Amylase (U/L), CFB, wk8 (N=75, N=76) | Amylase (U/L), CFB, wk12 (N=75, N=75) | Amylase (U/L), CFB, wk18 (N=68, N=70) | Amylase (U/L), CFB, wk24 (N=12, N=4) | Amylase (U/L), CFB, wk28 (N=5, N=3) | Amylase (U/L), CFB, wk36 (N=4, N=2) | Amylase (U/L), CFB, EoT (N=67, N=73) |
|---|
| Faldaprevir 120mg (12 Weeks) | 0 | -24 | -25 | -22 | -24 | -25 | -23 | -20 | -21 | -25 | 1 | -37 | -37 | -36 | -37 | -41 | -40 | -45 | -47 | -42 | 1 | 5 | 7 | 7 | 5 | -2 | -14 | -2 | -5 | 1 | -5 | -34 | -59 | -76 | -71 | -62 | -118 | -52 | -23 | -39 | -2 | -59 | -69 | -92 | -98 | -93 | -69 | -48 | -68 | -89 | -2 | 5 | -1 | -11 | -12 | -13 | 2 | -1 | -4 | -6 | 1 | 5 | 2 | -5 | -10 | -7 | -14 | -21 | -35 | 0 |
,| Faldaprevir 120mg (24 Weeks) | -5 | -29 | -29 | -27 | -27 | -30 | -10 | -16 | 11 | -27 | -2 | -34 | -34 | -35 | -36 | -42 | -24 | -22 | -6 | -42 | 1 | 7 | 10 | 9 | 6 | 5 | 13 | 15 | 18 | 5 | -5 | -38 | -60 | -70 | -69 | -64 | -131 | -113 | -14 | -59 | 30 | -41 | -62 | -75 | -84 | -60 | -42 | -32 | -37 | -21 | 26 | 9 | 6 | 2 | 4 | -4 | -17 | 0 | -15 | -5 | 7 | 3 | 5 | -2 | -4 | -7 | -16 | -8 | -19 | -4 |
End of Treatment Response (ETR)
End of Treatment Response (ETR): The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at end of all therapy. (NCT00984620)
Timeframe: up to 48 weeks
| Intervention | participants (Number) |
|---|
| Faldaprevir 120 mg (12 Weeks) | 65 |
| Faldaprevir 120 mg (24 Weeks) | 67 |
Rapid Virological Response at Week 4 (RVR)
Rapid virological response at week 4 (RVR): The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at week 4. (NCT00984620)
Timeframe: 4 weeks
| Intervention | participants (Number) |
|---|
| Faldaprevir 120 mg (12 Weeks) | 48 |
| Faldaprevir 120 mg (24 Weeks) | 56 |
Virological Response at Week 24 (W24VR)
virological response at week 24 (W24VR): The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at week 24. (NCT00984620)
Timeframe: 24 weeks
| Intervention | participants (Number) |
|---|
| Faldaprevir 120 mg (12 Weeks) | 59 |
| Faldaprevir 120 mg (24 Weeks) | 63 |
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (4)
Change from baseline (CFB) in Sodium, Bicarbonate, Cholesterol total, Triglyceride, and Glucose. (NCT00984620)
Timeframe: baseline and 48 weeks
| Intervention | mmol/L (Mean) |
|---|
| Sodium (mmol/L) CFB, Day 1(N=77, N=74) | Sodium (mmol/L) CFB, wk2 (N=76, N=78) | Sodium (mmol/L) CFB, wk4 (N=76, N=77) | Sodium (mmol/L) CFB, wk8 (N=73, N=76) | Sodium (mmol/L) CFB, wk12 (N=75, N=76) | Sodium (mmol/L) CFB, wk18 (N=68, N=70) | Sodium (mmol/L) CFB, wk24 (N=12, N=4) | Sodium (mmol/L) CFB, wk28 (N=5, N=3) | Sodium (mmol/L) CFB, wk36 (N=4, N=2) | Sodium (mmol/L) CFB, EoT (N=67, N=73) | Bicarbonate (mmol/L), CFB, day1 (N=76, N=75) | Bicarbonate (mmol/L), CFB, wk2 (N=75, N=78) | Bicarbonate (mmol/L), CFB, wk4 (N=74, N=77) | Bicarbonate (mmol/L), CFB, wk8 (N=74, N=76) | Bicarbonate (mmol/L), CFB, wk12 (N=74, N=76) | Bicarbonate (mmol/L), CFB, wk18 (N=66, N=69) | Bicarbonate (mmol/L), CFB, wk24 (N=12, N=4) | Bicarbonate (mmol/L), CFB, wk28 (N=4, N=3) | Bicarbonate (mmol/L), CFB, wk36 (N=4, N=2) | Bicarbonate (mmol/L), CFB, EoT (N=64, N=71) | Cholesterol tot. (mmol/L), CFB, day1 (n=77, N=75) | Cholesterol tot. (mmol/L), CFB, wk2 (n=76, N=78) | Cholesterol tot. (mmol/L), CFB, wk4 (n=76, N=77) | Cholesterol tot. (mmol/L), CFB, wk8 (n=75, N=76) | Cholesterol tot. (mmol/L), CFB, wk12 (n=75, N=76) | Cholesterol tot. (mmol/L), CFB, wk18 (n=68, N=70) | Cholesterol tot. (mmol/L), CFB, wk24 (n=12, N=4) | Cholesterol tot. (mmol/L), CFB, wk28 (n=5, N=3) | Cholesterol tot. (mmol/L), CFB, wk36 (n=4, N=2) | Cholesterol tot. (mmol/L), CFB, EoT (n=67, N=73) | Triglyceride (mmol/L), CFB, day1 (N=77, N=75) | Triglyceride (mmol/L), CFB, wk2 (N=76, N=78) | Triglyceride (mmol/L), CFB, wk4 (N=76, N=77) | Triglyceride (mmol/L), CFB, wk8 (N=75, N=76) | Triglyceride (mmol/L), CFB, wk12 (N=75, N=76) | Triglyceride (mmol/L), CFB, wk18 (N=68, N=70) | Triglyceride (mmol/L), CFB, wk24 (N=12, N=4) | Triglyceride (mmol/L), CFB, wk28 (N=5, N=3) | Triglyceride (mmol/L), CFB, wk36 (N=4, N=2) | Triglyceride (mmol/L), CFB, EoT (N=67, N=73) | Glucose (mmol/L), CFB, day1 (N=76, N=75) | Glucose (mmol/L), CFB, wk2 (N=75, N=78) | Glucose (mmol/L), CFB, wk4 (N=74, N=77) | Glucose (mmol/L), CFB, wk8 (N=74, N=76) | Glucose (mmol/L), CFB, wk12 (N=73, N=76) | Glucose (mmol/L), CFB, wk18 (N=67, N=70) | Glucose (mmol/L), CFB, wk24 (N=12, N=4) | Glucose (mmol/L), CFB, wk28 (N=5, N=3) | Glucose (mmol/L), CFB, wk36 (N=4, N=2) | Glucose (mmol/L), CFB, EoT (N=66, N=71) |
|---|
| Faldaprevir 120mg (12 Weeks) | 0 | 0 | 0 | 1 | 0 | 0 | -1 | -2 | -1 | 0 | 0.1 | -0.2 | -0.1 | -0.1 | -0.3 | -0.3 | -0.4 | -1.2 | -2.6 | -0.2 | 0.03 | -0.48 | -0.51 | -0.58 | -0.64 | -0.51 | -0.36 | 0.10 | -0.35 | -0.43 | -0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.0 | -0.2 | 0.0 | -0.3 | 0.1 | -0.1 | -0.1 | -0.2 | -0.1 | -0.3 | -0.4 | -0.7 | -0.4 | -0.1 | -0.4 |
,| Faldaprevir 120mg (24 Weeks) | 1 | 0 | 0 | 1 | 1 | 0 | 0 | -1 | -1 | 0 | 0.2 | 0.0 | -0.1 | 0.0 | -0.4 | -0.4 | -0.5 | -0.2 | -1.0 | -0.1 | -0.05 | -0.54 | -0.67 | -0.60 | -0.74 | -0.80 | -0.37 | -0.09 | -0.23 | -0.74 | -0.1 | 0.1 | 0.2 | 0.1 | 0.1 | 0.2 | 0.2 | 0.4 | 0.1 | 0.1 | 0.2 | 0.1 | 0.1 | 0.1 | -0.1 | -0.1 | -0.4 | 0.1 | -0.1 | -0.1 |
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (3)
Change from baseline (CFB) in Platelets and white blood cells. (NCT00984620)
Timeframe: baseline and 48 weeks
| Intervention | 10^9 cells/L (Mean) |
|---|
| Platelets CFB, Day 1 (N=77, N=73) | Platelets CFB, wk2 (N=74, N=74) | Platelets CFB, wk4 (N=73, N=74) | Platelets CFB, wk8 (N=73, N=71) | Platelets CFB, wk12 (N=72, N=72) | Platelets CFB, wk18 (N=66, N=68) | Platelets CFB, wk24 (N=12, N=3) | Platelets CFB, wk28 (N=4, N=2) | Platelets CFB, wk36 (N=4, N=2) | Platelets CFB, EoT (N=67, N=71) | white blood cell CFB, day1 (N=77, N=75) | white blood cell CFB, wk2 (N=75, N=77) | white blood cell CFB, wk4 (N=74, N=76) | white blood cell CFB, wk8 (N=75, N=74) | white blood cell CFB, wk12 (N=74, N=74) | white blood cell CFB, wk18 (N=66, N=69) | white blood cell CFB, wk24 (N=12, N=4) | white blood cell CFB, wk28 (N=4, N=3) | white blood cell CFB, wk36 (N=4, N=2) | white blood cell CFB, EoT (N=67, N=73) |
|---|
| Faldaprevir 120mg (12 Weeks) | 3 | -35 | -35 | -55 | -61 | -55 | -46 | -22 | -47 | -59 | -0.1 | -2.2 | -2.6 | -3.2 | -3.4 | -3.2 | -4.0 | -2.8 | -2.5 | -3.4 |
,| Faldaprevir 120mg (24 Weeks) | 2 | -35 | -39 | -48 | -50 | -51 | -50 | -83 | -85 | -50 | 0.3 | -1.8 | -2.6 | -2.9 | -2.8 | -3.1 | -2.0 | -1.9 | -3.0 | -3.1 |
Sustained Virological Response (SVR24) at 24 Weeks After Completion of All Therapy
Sustained Virological Response (SVR24) at 24 weeks: The patients who reached plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at 24 weeks after completion of all Hepatitis C virus (HCV) therapy. (NCT00984620)
Timeframe: 72 weeks
| Intervention | participants (Number) |
|---|
| Faldaprevir 120 mg (12 Weeks) | 54 |
| Faldaprevir 120 mg (24 Weeks) | 58 |
Virological Response at Week 28 (W28VR)
Virological response at Week 28: The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at Week 28. (NCT00984620)
Timeframe: 28 weeks
| Intervention | participants (Number) |
|---|
| Faldaprevir 120 mg (12 Weeks) | 61 |
| Faldaprevir 120 mg (24 Weeks) | 60 |
Virological Response at Week 36 (W36VR)
Virological response at week 36 (W36VR): the patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at week 36. (NCT00984620)
Timeframe: 36 weeks
| Intervention | participants (Number) |
|---|
| Faldaprevir 120 mg (12 Weeks) | 55 |
| Faldaprevir 120 mg (24 Weeks) | 58 |
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (2)
Change from baseline (CFB) in haematocrit and Eosinophils. (NCT00984620)
Timeframe: baseline and 48 weeks
| Intervention | % of laboratory test substance (Mean) |
|---|
| haematocrit (%) CFB, Day1 (N=77, N=75) | haematocrit (%) CFB, wk2 (N=75, N=77) | haematocrit (%) CFB, wk4 (N=74, N=76) | haematocrit (%) CFB, wk8 (N=75, N=74) | haematocrit (%) CFB, wk12 (N=72, N=74) | haematocrit (%) CFB, wk18 (N=66, N=69) | haematocrit (%) CFB, wk24 (N=11, N=4) | haematocrit (%) CFB, wk28 (N=4, N=3) | haematocrit (%) CFB, wk36 (N=4, N=2) | haematocrit (%) CFB, EoT (N=66, N=70) | Eosinophils(%), CFB, day1 (N=77, N=75) | Eosinophils(%), CFB, wk2 (N=75, N=76) | Eosinophils(%), CFB, wk4 (N=73, N=74) | Eosinophils(%), CFB, wk8 (N=74, N=73) | Eosinophils(%), CFB, wk12 (N=72, N=72) | Eosinophils(%), CFB, wk18 (N=62, N=65) | Eosinophils(%), CFB, wk24 (N=12, N=4) | Eosinophils(%), CFB, wk28 (N=4, N=3) | Eosinophils(%), CFB, wk36 (N=4, N=2) | Eosinophils(%), CFB, EoT (N=66, N=70) |
|---|
| Faldaprevir 120mg (12 Weeks) | -0.9 | -4.3 | -8.0 | -8.4 | -8.5 | -7.3 | -6.6 | -3.8 | -3.0 | -6.0 | 0 | 0 | -1 | 0 | 0 | 0 | -1 | -1 | -1 | 0 |
,| Faldaprevir 120mg (24 Weeks) | -1.3 | -4.7 | -7.9 | -7.1 | -7.8 | -6.5 | -2.7 | -1.2 | -3.6 | -6.0 | 0 | 0 | 0 | 0 | 0 | 0 | -1 | -2 | -1 | 1 |
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (1)
Change from baseline (CFB) in Red blood cells. (NCT00984620)
Timeframe: baseline and 48 weeks
| Intervention | 10^12 cells/L (Mean) |
|---|
| Red blood cell (10^12cells/L) CFB,Day 1(N=77,N=75) | Red blood cell (10^12cells/L) CFB, wk2 (N=75,N=77) | Red blood cell (10^12cells/L) CFB, wk4(N=74, N=76) | Red blood cell (10^12cells/L) CFB, wk8(N=75, N=74) | Red blood cell (10^12cells/L) CFB, wk12(N=74,N=74) | Red blood cell (10^12cells/L) CFB, wk18(N=66,N=69) | Red blood cell (10^12cells/L) CFB, wk24(N=12, N=4) | Red blood cell (10^12cells/L) CFB, wk28(N=4, N=3) | Red blood cell (10^12cells/L) CFB, wk36(N=4, N=2) | Red blood cell (10^12cells/L) CFB, EoT(N=67, N=73) |
|---|
| Faldaprevir 120mg (12 Weeks) | 0.0 | -0.3 | -0.8 | -1.0 | -1.1 | -1.2 | -1.2 | -1.1 | -0.9 | -1.2 |
,| Faldaprevir 120mg (24 Weeks) | -0.1 | -0.4 | -0.8 | -1.0 | -1.2 | -1.2 | -0.9 | -0.9 | -1.4 | -1.2 |
Percent Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) From Study Entry
HOMA-IR was calculated as [fasting glucose (mg/dL) x fasting insulin (uIU/mL)]/405. Percent Change in HOMA-IR was calculated as HOMA-IR at later time point (16, 28, 52, 76) minus HOMA-IR at study entry, divided by HOMA-IR at study entry x 100%. Study protocol required fasting for at least 8 hours (nothing by mouth except medications and water) prior to specimen collection for fasting insulin and fasting glucose testing. (NCT00991289)
Timeframe: Weeks 0, 16, 28, 52, and 76
| Intervention | percentage of HOMA-IR at study entry (Median) |
|---|
| Percent change in HOMA-IR at Week 16 (n=56) | Percent change in HOMA-IR at Week 28 (n=39) | Percent change in HOMA-IR at Week 52 (n=27) | Percent change in HOMA-IR at Week 76 (n=22) |
|---|
| NTZ/PEG/RBV | -13.0 | -6.3 | 23.2 | 9.5 |
Change in Hemoglobin Level From Study Entry
Change in hemoglobin (HGB) was calculated as HGB at later time point (Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76) minus HGB at study entry. (NCT00991289)
Timeframe: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76.
| Intervention | g/dL (Median) |
|---|
| Change in HGB at Week 4 | Change in HGB at Week 8 | Change in HGB at Week 12 | Change in HGB at Week 16 | Change in HGB at Week 20 | Change in HGB at Week 24 | Change in HGB at Week 28 | Change in HGB at Week 32 | Change in HGB at Week 36 | Change in HGB at Week 40 | Change in HGB at Week 44 | Change in HGB at Week 48 | Change in HGB at Week 52 | Change in HGB at Week 76 |
|---|
| NTZ/PEG/RBV | -0.1 | -2.1 | -2.5 | -2.5 | -2.5 | -2.4 | -2.5 | -2.7 | -2.5 | -2.6 | -2.6 | -2.7 | -2.9 | -0.9 |
Number of Participants With Adverse Events of Grade 2 or Higher
Number of participants who experienced an adverse event of Grade 2 or higher at any time after study entry. Grading of adverse events (signs and symptoms and laboratory toxicities) was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004. (NCT00991289)
Timeframe: From study entry to up to week 76
| Intervention | participants (Number) |
|---|
| NTZ/PEG/RBV | 65 |
Number of Participants With HCV Genotype 1
Confirmatory HCV genotyping was performed on stored plasma from entry using VERSANT HCV Genotype assay v2.0 (LiPA, RUO, Siemens Healthcare Diagnostics Inc., Tarrytown, NY). (NCT00991289)
Timeframe: Week 0
| Intervention | participants (Number) |
|---|
| NTZ/PEG/RBV | 67 |
Percentage of Participants With Complete Early Virologic Response (cEVR)
Complete early virologic response (cEVR) was defined as undetectable HCV viral load (<43 IU/ml) at week 16, where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test). (NCT00991289)
Timeframe: Week 16
| Intervention | percentage of participants (Number) |
|---|
| NTZ/PEG/RBV | 38.8 |
Percentage of Participants With Early Virologic Response (EVR)
Early virologic response (EVR) was defined as undetectable HCV viral load (<43 IU/ml) at Week 16 or at least a 2-log10 decrease in HCV viral load from study entry at Week 16, where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test). (NCT00991289)
Timeframe: Weeks 0, 16
| Intervention | percentage of participants (Number) |
|---|
| NTZ/PEG/RBV | 65.7 |
Percent Change in Fasting Insulin Level From Study Entry
Percent Change in fasting insulin (FINS) was calculated as FINS at later time point (16, 28, 52, 76) minus FINS at study entry, divided by FINS at study entry x 100%. Study protocol required fasting for at least 8 hours (nothing by mouth except medications and water) prior to specimen collection for fasting insulin testing. (NCT00991289)
Timeframe: Weeks 0, 16, 28, 52, and 76
| Intervention | percentage of FINS at study entry (Median) |
|---|
| Percent change in FINS at Week 16 | Percent change in FINS at Week 28 | Percent change in FINS at Week 52 | Percent change in FINS at Week 76 |
|---|
| NTZ/PEG/RBV | 0 | 8.8 | 28.2 | 8.3 |
Change in log10 HCV Viral Load After 4 Weeks of Nitazoxanide (NTZ) Monotherapy.
Change in log10 HCV viral load was calculated as log10-transformed HCV viral load at Week 4 minus log10-transformed HCV viral load at study entry. HCV viral load testing was done using Cobas AmpliPrep/Taqman HCV Test. (NCT00991289)
Timeframe: Weeks 0, 4
| Intervention | log10 IU/mL (Median) |
|---|
| NTZ/PEG/RBV | -0.12 |
Percentage of Participants With Sustained Virologic Response (SVR)
Sustained virologic response (SVR) was defined as undetectable HCV viral load (<43 IU/ml) at 24 weeks after treatment discontinuation, where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test). Participants who failed to achieve EVR or had detectable HCV RNA at Week 28 and per protocol discontinued study, and participants without HCV RNA from 24 weeks after treatment discontinuation, were considered non-responders. (NCT00991289)
Timeframe: 24 weeks after treatment discontinuation
| Intervention | percentage of participants (Number) |
|---|
| NTZ/PEG/RBV | 32.8 |
Percent Change in Fasting Glucose Level From Study Entry
Percent Change in fasting glucose (FGLUC) was calculated as FGLUC at later time point (16, 28, 52, 76) minus FGLUC at study entry, divided by FGLUC at study entry x 100%. Study protocol required fasting for at least 8 hours (nothing by mouth except medications and water) prior to specimen collection for fasting glucose testing. (NCT00991289)
Timeframe: Weeks 0, 16, 28, 52, and 76
| Intervention | percentage of FGLUC at study entry (Median) |
|---|
| Percent change in FGLUC at Week 16 | Percent change in FGLUC at Week 28 | Percent change in FGLUC at Week 52 | Percent change in FGLUC at Week 76 |
|---|
| NTZ/PEG/RBV | -3.2 | -5.3 | 1.1 | 0 |
Percentage of Participants With Rapid Virologic Response (RVR)
Rapid virologic response (RVR) was defined as undetectable HCV viral load (<43 IU/ml) at Week 8 where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test). (NCT00991289)
Timeframe: Week 8
| Intervention | percentage of participants (Number) |
|---|
| NTZ/PEG/RBV | 10.4 |
Percentage of Participants Achieving Extended Rapid Virologic Response (eRVR)
The table below shows the percentage of participants who had a Extended Rapid Virologic Response (eRVR) (ie, those with undetectable hepatitis C virus [HCV] ribonucleic acid [RNA values of <25 IU/mL, target not detected at at Weeks 4 and 12 of treatment). (NCT01054573)
Timeframe: Weeks 4 and 12
| Intervention | Percentage of participants (Number) |
|---|
| Phase 3: T12(Q8h)/PR - Prior Null Responder | 34.4 |
| Phase 3: T12(Q8h)/PR - Prior Partial Responder | 72.7 |
| Phase 3: T12(Q8h)/PR - Prior Relapser | 85.2 |
| Phase 1: T12(Q8h)/PR | 33.3 |
Percentage of Participants Who Relapsed During Follow-Up
The table below shows the percentage of participants who relapsed (ie, those having confirmed detectable hepatitis C virus [HCV] ribonucleic acid [RNA] during the 24-week follow-up period after previous HCV RNA <25 IU/mL, target not detected, at end of treatment). (NCT01054573)
Timeframe: During Follow-Up (24 weeks after the last dose of study drug, administerd at 48 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Phase 3: T12(Q8h)/PR - Prior Null Responder | 21.4 |
| Phase 3: T12(Q8h)/PR - Prior Partial Responder | 5.3 |
| Phase 3: T12(Q8h)/PR - Prior Relapser | 4.0 |
| Phase 1: T12(Q8h)/PR | 28.6 |
The Percentage of Participants Achieving a Sustained Virologic Response (SVR) 24 Weeks After the Last Dose of Study Drug (SVR24 Actual)
The table below shows the percentage of participants acheiving a SVR 24 weeks after the last dose of study drug defined as having plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels < 25 IU/mL, target not detected at end of treatment (EOT) AND the participant did not relapse AND the participant completed the treatment; OR if the participant had plasma HCV RNA levels of < 25 IU/mL, target not detected at EOT AND the participant did not relapse AND the participant prematurely discontinued at least one study medication, but never for the reason virologic failure. (NCT01054573)
Timeframe: End of trial (24 weeks after last dose, administerd at 48 weeks)
| Intervention | Percentage of participants with response (Number) |
|---|
| Phase 3: T12(Q8h)/PR - Prior Null Responder | 34.4 |
| Phase 3: T12(Q8h)/PR - Prior Partial Responder | 72.7 |
| Phase 3: T12(Q8h)/PR - Prior Relapser | 81.5 |
| Phase 1: T12(Q8h)/PR | 44.4 |
Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level
The table below shows change from baseline in log 10 plasma HCV RNA values measured over time. (NCT01054573)
Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48
| Intervention | log 10 IU/ml (Median) |
|---|
| Week 4 (n=32, 22, 26, and 9) | Week 8 (n=32, 22, 26, and 9) | Week 12 (n=31, 22, 26, 9) | Week 24 (n=23, 20, 24, and 8) | Week 36 (n=18, 19, 23, and 7) | Week 48 (n=15, 16, 21, and 7) |
|---|
| Phase 1: T12(Q8h)/PR | -5.55 | -5.96 | -5.96 | -5.87 | -6.07 | -6.07 |
,| Phase 3: T12(Q8h)/PR - Prior Null Responder | -5.39 | -5.51 | -5.40 | -5.89 | -5.95 | -6.03 |
,| Phase 3: T12(Q8h)/PR - Prior Partial Responder | -5.83 | -5.88 | -5.88 | -5.72 | -5.86 | -5.88 |
,| Phase 3: T12(Q8h)/PR - Prior Relapser | -5.59 | -5.62 | -5.62 | -5.75 | -5.78 | -5.71 |
Percentage of Participants Who Met a Virologic Stopping Rule That Required Them to Permanently Discontinue Telaprevir and Continue Pegylated Interferon (Peg-IFN) and Ribavirin (RBV) at Week 4 or Week 8
The table below shows the percentage of participants at Week 4 or 8 who met a stopping rule defined as having a hepatitis C virus (HCV) ribonucleic acid (RNA) value >100 IU/mL. (NCT01054573)
Timeframe: Week 4, Week 8
| Intervention | Percentage of participants (Number) |
|---|
| Phase 3: T12(Q8h)/PR - Prior Null Responder | 28.1 |
| Phase 3: T12(Q8h)/PR - Prior Partial Responder | 4.5 |
| Phase 3: T12(Q8h)/PR - Prior Relapser | 3.7 |
| Phase 1: T12(Q8h)/PR | 11.1 |
Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values Over Time
The table below shows plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) values measured over time. (NCT01054573)
Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, 48
| Intervention | Log 10 IU/mL (Median) |
|---|
| Baseline (n=32, 22, 27, and 9) | Week 4 (n=32, 22, 26, and 9) | Week 8 (n=32, 22, 26, and 9) | Week 12 (n=31, 22, 26, and 9) | Week 24 (n=23, 20, 26, and 8) | Week 36 (n=18, 19, 23, and 7) | Week 48 (n=16, 16, 21, and 7) |
|---|
| Phase 1: T12(Q8h)/PR | 6.76 | 1.24 | 0.70 | 0.70 | 0.70 | 0.70 | 0.70 |
,| Phase 3: T12(Q8h)/PR - Prior Null Responder | 6.63 | 1.24 | 0.70 | 0.70 | 0.70 | 0.70 | 0.70 |
,| Phase 3: T12(Q8h)/PR - Prior Partial Responder | 6.72 | 0.70 | 0.70 | 0.70 | 0.70 | 0.70 | 0.70 |
,| Phase 3: T12(Q8h)/PR - Prior Relapser | 6.48 | 0.70 | 0.70 | 0.70 | 0.70 | 0.70 | 0.70 |
Percentage of Participants Who Met a Virologic Stopping Rule That Required Them to Permanently Discontinue All Study Drugs at Week 12, 24, or 36
The table below shows the percentage of participants at Week 12, 24, and 36 who met a stopping rule. The stopping rule at Week 12 was having hepatitis C virus (HCV) ribonucleic acid (RNA) value of >100 IU/mL and the stopping rule at Weeks 24 or 36 was having a HCV RNA value of >=25 IU/mL. (NCT01054573)
Timeframe: Week 12 or Weeks 24 or 36
| Intervention | Percentage of participants (Number) |
|---|
| Week 12 | Week 24 | Week 36 |
|---|
| Phase 1: T12(Q8h)/PR | 11.1 | 11.1 | 0 |
,| Phase 3: T12(Q8h)/PR - Prior Null Responder | 31.2 | 9.4 | 9.4 |
,| Phase 3: T12(Q8h)/PR - Prior Partial Responder | 4.5 | 9.1 | 0 |
,| Phase 3: T12(Q8h)/PR - Prior Relapser | 0 | 3.7 | 0 |
Percentage of Participants With Viral Breakthrough
The table below shows the percentage of participants with viral breakthrough defined as a confirmed increase >1 log10 in hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached during the considered treatment phase up to the considered time point, if the lowest level reached is > 25 IU/mL, or a confirmed value of HCV RNA >100 IU/mL in participants whose HCV RNA had previously become <25 IU/mL (detected or target not detected) during the considered treatment phase. (NCT01054573)
Timeframe: Week 48 (Period After Telaprevir Intake) and Week 12 (Telaprevir Treatment Phase)
| Intervention | Percentage of participants (Number) |
|---|
| Week 48 (Period After Telaprevir Intake) | Week 12 (Telaprevir Treatment Phase) |
|---|
| Phase 1: T12(Q8h)/PR | 11.1 | 11.1 |
,| Phase 3: T12(Q8h)/PR - Prior Null Responder | 25.0 | 15.6 |
,| Phase 3: T12(Q8h)/PR - Prior Partial Responder | 9.1 | 4.5 |
,| Phase 3: T12(Q8h)/PR - Prior Relapser | 3.7 | 0.0 |
Percentage of Participants Achieving Rapid Virologic Response (RVR)
The table below shows the percentage of participants who had a rapid virologic response (RVR) (ie, those with undetectable hepatitis C virus [HCV] ribonucleic acid [RNA values of <25 IU/mL, target not detected at Week 4 of treatment). (NCT01054573)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| Phase 3: T12(Q8h)/PR - Prior Null Responder | 37.5 |
| Phase 3: T12(Q8h)/PR - Prior Partial Responder | 77.3 |
| Phase 3: T12(Q8h)/PR - Prior Relapser | 85.2 |
| Phase 1: T12(Q8h)/PR | 33.3 |
The Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected at Different Time Points
The table below shows the percentage of participants with undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels of less than 25 IU/ml, target not detected at different time points during the study. Data was imputed for participants with missing values using the last observation carried forward (LOCF) method for missing values. (NCT01054573)
Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48, and at the end of treatment (Week 48 or at time of early discontinuation)
| Intervention | Percentage of participants with response (Number) |
|---|
| Basline | Week 4 | Week 8 | Week 12 | Week 24 | Week 36 | Week 48 | End of Treatment |
|---|
| Phase 1: T12(Q8h)/PR | 0 | 33.3 | 66.7 | 66.7 | 66.7 | 77.8 | 77.8 | 77.8 |
,| Phase 3: T12(Q8h)/PR - Prior Null Responder | 0 | 37.5 | 56.3 | 59.4 | 50.0 | 43.8 | 43.8 | 43.8 |
,| Phase 3: T12(Q8h)/PR - Prior Partial Responder | 0 | 77.3 | 86.4 | 90.9 | 77.3 | 81.8 | 72.7 | 86.4 |
,| Phase 3: T12(Q8h)/PR - Prior Relapser | 0 | 85.2 | 92.6 | 92.6 | 85.2 | 85.2 | 85.2 | 92.6 |
Incidence of Treatment-emergent Serious Adverse Events (SAEs)
An SAE was defined as any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event; however, this does not include an event that, had it occurred in a more severe form, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also have been any other medically important event that, in the opinion of the Investigator, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed in the definition above. See Adverse Events section below for further details. (NCT01058005)
Timeframe: up to 108 Weeks
| Intervention | participants (Number) |
|---|
| Natalizumab | 1 |
| Interferon Beta-1a | 1 |
| Glatiramer Acetate | 0 |
Proportion of Participants Relapse-free at Week 144
Relapses are defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. Only relapses confirmed by INEC are included in this analysis. Data after participants switched to alternative MS medications are excluded. The estimated proportion of subjects relapse-free at Week 144 is based on the Kaplan-Meier product limit method. (NCT01064401)
Timeframe: 144 weeks
| Intervention | proportion of participants (Number) |
|---|
| Interferon Beta-1a | 0.508 |
| Daclizumab High Yield Process | 0.673 |
Percentage of Participants With a ≥ 7.5 Point Worsening From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Impact Score at 96 Weeks
The MSIS-29 is a 29-item disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures physical and psychological items. Worsening in the MSIS-29 physical score is defined as an increase of ≥ 7.5 points in the MSIS-29 physical score at 96 weeks compared to baseline. If a participant was missing data for less than 10 of the 20 items that make up the physical score, then the mean of the non-missing items were used for the missing items. If a participant was missing 10 or more of the 20 items that make up the physical score, or missing the questionnaire entirely, or if the questionnaire was completed after the participant switched to alternative MS medication, a random effects model was used to estimate the MSIS-29 physical score. (NCT01064401)
Timeframe: Baseline and 96 weeks
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a | 23 |
| Daclizumab High Yield Process | 19 |
Adjusted Mean Number of New or Newly Enlarging T2 Hyperintense Lesions up to Week 96
The quantity of lesions is assessed by brain magnetic resonance imaging (MRI). The adjusted mean number is estimated from a negative binomial regression model, adjusted for baseline volume of T2 from a negative binomial regression model, adjusted for baseline volume of T2 hyperintense lesions, history of prior IFN beta use and baseline age (≤ 35 vs > 35 years). To account for the timing of the MRI measurement, the logarithmic transformation of the scan number of the MRI assessment is included in the model as the 'offset' parameter. Observed data after participants switched to alternative MS medications are excluded. Missing data are not imputed. Only observed new or newly enlarging T2 lesions at the last visit of the participant up to Week 96 visit are used in this analysis. (NCT01064401)
Timeframe: up to 96 weeks
| Intervention | lesions (Mean) |
|---|
| Interferon Beta-1a | 9.44 |
| Daclizumab High Yield Process | 4.31 |
Adjusted Annualized Relapse Rate (ARR)
Relapses are defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. Only relapses confirmed by Independent Neurology Evaluation Committee (INEC) are included in this analysis. Adjusted ARR was estimated from a negative binomial regression model adjusted for the baseline relapse rate, history of prior IFN beta use, baseline Expanded Disability Status Scale score (EDSS; ≤ 2.5 vs > 2.5) and baseline age (≤ 35 vs > 35 years). Data after participants switched to alternative MS medications are excluded. (NCT01064401)
Timeframe: Up to 144 weeks
| Intervention | relapses per person-years (Number) |
|---|
| Interferon Beta-1a | 0.393 |
| Daclizumab High Yield Process | 0.216 |
Proportion of Participants With Sustained Disability Progression at 144 Weeks
Sustained disability progression is defined as: at least a 1.0-point increase on the EDSS from Baseline EDSS ≥ 1.0 that is sustained for 12 weeks, or at least a 1.5-point increase on the EDSS from baseline EDSS = 0 that is sustained for 12 weeks. The EDSS measures the disability status of people with MS on a scale that ranges from 0 to 10, with higher scores indicating more disability. Estimated proportion of participants with progression is based on the Kaplan-Meier product limit method. Participants were censored at the time of withdrawal/switch if they withdrew from study or switched to alternative MS medication without a progression. Participants with a tentative progression at the End of Treatment Period Visit (or the last EDSS assessment prior to alternative MS start date) and no confirmation assessment were censored at their last EDSS assessment. (NCT01064401)
Timeframe: Baseline through 144 weeks
| Intervention | proportion of participants (Number) |
|---|
| Interferon Beta-1a | 0.203 |
| Daclizumab High Yield Process | 0.162 |
Time Course to Return of Radiological and/or Clinical Evidence of Multiple Sclerosis Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) and/or Clinical Relapse Rescue Criteria.
Rescue criteria were: 1) central reader MRI finding of 1 new gadolinium-enhancing (Gd+) lesion of >0.8 cubic centimeters in volume or 2 or more Gd+ lesions of any size 2) clinical relapse. Clinical relapse was new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, as defined by: an increase of ≥1 grade in ≥2 functional scales of the Expanded Disability Status Scale (EDSS); an increase of ≥2 grades in 1 functional scale of the EDSS; or an increase of >0.5 in EDSS if the previous EDSS was ≤5.5, or ≥0.5 if the previous EDSS was >5.5 (NCT01071083)
Timeframe: 28 Weeks
| Intervention | Percentage of subjects meeting criteria (Number) |
|---|
| Natalizumab | 4.7 |
| Intravenous Placebo | 60.5 |
| Interferon β-1a | 28.6 |
| Glatiramer Acetate | 53.3 |
| Methylprednisolone | 54.8 |
Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria.
MRI rescue criteria were the presence of 1 new gadolinium-enhancing (Gd+) lesion of >0.8 cubic centimeters in volume or 2 or more Gd+ lesions of any size, according to the central MRI reader. (NCT01071083)
Timeframe: 28 Weeks
| Intervention | Percentage of subjects meeting criteria (Number) |
|---|
| Natalizumab | 0.0 |
| Intravenous Placebo | 52.5 |
| Interferon β-1a | 8.3 |
| Glatiramer Acetate | 49.7 |
| Methylprednisolone | 46.1 |
Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score
ADAS-NonCog is a subscale of ADAS aimed to evaluate the non-cognitive features such as mood state and behavioral changes. It takes about 10 minutes to be performed and includes 10 items: testing tearful, depressed mood, concentration/distractibility, uncooperative to testing, delusions, hallucinations, pacing, motor activity increase, tremors and appetite change. Scores range between 0 (excellent performance) and 35 (worst performance). (NCT01075763)
Timeframe: Baseline, Week 12, 28 and 52
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Week 12 | Week 28 | Week 52 |
|---|
| Placebo | 6.07 | 4.73 | 5.20 | 7.20 |
,| Rebif 22 Mcg | 4.37 | 3.53 | 4.63 | 5.47 |
Global Deterioration Scale Score
"Global deterioration scale includes seven different diagnostic stages ranging between no cognitive deterioration and very serious cognitive deterioration. It investigates the cognitive impairment. Scores range between 1 (no cognitive deterioration) and 7 (very severe cognitive decline)." (NCT01075763)
Timeframe: Baseline, Week 28 and 52
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Week 28 | Week 52 |
|---|
| Placebo | 2.87 | 3.00 | 3.20 |
,| Rebif 22 Mcg | 3.00 | 3.05 | 3.26 |
Geriatric Depression Scale (GDS) Score
The GDS consists of 30 'yes' or 'no' items aimed to assess depression. One point is assigned to each answer and the cumulative score is rated on a scoring grid. Scores are grouped as follows: 0-9 'normal', 10-19 'mildly depressed', and 20-30 'severely depressed'. (NCT01075763)
Timeframe: Baseline, Week 28 and 52
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Week 28 | Week 52 |
|---|
| Placebo | 10.67 | 9.07 | 7.50 |
,| Rebif 22 Mcg | 10.11 | 9.68 | 10.79 |
Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score
CIBIC-PLUS: structured instrument based on comprehensive evaluation of 3 domains: participant cognition, behavior and functioning, including assessment of daily living activities. It includes 15 items and represents assessment of skilled clinician using validated scales based on the observation at interviews conducted separately with participant and caregiver familiar with behavior of participant. According to comparison between baseline and follow-up assessments, scores can range between 1 (markedly improved) and 7 (markedly worsened), with 4 indicating no change observed between two visits. (NCT01075763)
Timeframe: Week 28 and 52
| Intervention | participants (Number) |
|---|
| Week 28: CIBIC-PLUS Score 1 | Week 28: CIBIC-PLUS Score 2 | Week 28: CIBIC-PLUS Score 3 | Week 28: CIBIC-PLUS Score 4 | Week 28: CIBIC-PLUS Score 5 | Week 28: CIBIC-PLUS Score 6 | Week 28: CIBIC-PLUS Score 7 | Week 52: CIBIC-PLUS Score 1 | Week 52: CIBIC-PLUS Score 2 | Week 52: CIBIC-PLUS Score 3 | Week 52: CIBIC-PLUS Score 4 | Week 52: CIBIC-PLUS Score 5 | Week 52: CIBIC-PLUS Score 6 | Week 52: CIBIC-PLUS Score 7 |
|---|
| Placebo | 0 | 2 | 6 | 5 | 0 | 2 | 0 | 0 | 2 | 2 | 4 | 4 | 3 | 0 |
,| Rebif 22 Mcg | 1 | 0 | 7 | 8 | 3 | 0 | 0 | 0 | 0 | 6 | 7 | 1 | 4 | 1 |
Mini Mental Status Examination (MMSE) Score
MMSE is a tool for screening cognitive decline associated with dementia. It is a brief examination intended to evaluate an adult participant's level of cognitive functioning. The test is performed in following areas: orientation in time and place, learning and immediate recall, mental control and concentration, short-term recall, naming ability, language expression, verbal comprehension, writing comprehension, writing ability and visual-spatial coordination. Scores range between 0 (maximum cognitive deficit) and 30 (no cognitive deficit). (NCT01075763)
Timeframe: Baseline, Week 12, 28 and 52
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Week 12 | Week 28 | Week 52 |
|---|
| Placebo | 22.93 | 24.66 | 23.66 | 21.98 |
,| Rebif 22 Mcg | 23.46 | 24.50 | 24.25 | 22.43 |
Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score
ADAS: global rating scale created to evaluate both cognitive and functional aspects linked with disease progression. ADAS-Cog: subscale of ADAS which consists in a series of short tests aimed to evaluate possible cognitive impairment due to disease progression. It includes 11 items, testing word-finding difficulty, following commands, naming: objects and fingers, orientation, word recognition, recall of test instructions, constructions, ideational praxis, spoken language ability, comprehension of spoken language and word recall. Scores range from 0 (no impairment) to 70 (serious deficit). (NCT01075763)
Timeframe: Week 12 and 28
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 28 |
|---|
| Placebo | 17.97 | 17.55 |
,| Rebif 22 Mcg | 16.74 | 18.49 |
Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score
ADAS: global rating scale created to evaluate both cognitive and functional aspects linked with disease progression. ADAS-Cog: subscale of ADAS which consists in a series of short tests aimed to evaluate possible cognitive impairment due to disease progression. It includes 11 items, testing word-finding difficulty, following commands, naming: objects and fingers, orientation, word recognition, recall of test instructions, constructions, ideational praxis, spoken language ability, comprehension of spoken language and word recall. Scores range from 0 (no impairment) to 70 (serious deficit). (NCT01075763)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Week 52 |
|---|
| Placebo | 19.81 | 20.33 |
,| Rebif 22 Mcg | 18.63 | 20.66 |
Instrumental Activities of Daily Living (IADL) Score
IADL is used to evaluate participants with early-stage disease, both to assess level of disease and to determine participant's ability of self-care. IADL scale measures functional impact of emotional, cognitive, and physical impairments. It provides information about participants' compromising rate and care he might need. It includes 8 items: testing ability to use telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, responsibility for own medication and ability to handle finances. Scores range between 0 (impairment) and 8 (full independence). (NCT01075763)
Timeframe: Baseline, Week 28 and 52
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Week 28 | Week 52 |
|---|
| Placebo | 6.20 | 5.60 | 5.67 |
,| Rebif 22 Mcg | 6.11 | 5.84 | 4.89 |
Physical Self-Maintenance Scale (PSMS) Score
PSMS designed as a disability measure for use in planning and evaluating treatment in elderly participants living in community or in institutions, is Guttman scale containing 6 items of self-care. The scale is based on theory that human behavior can be ordered in a hierarchy of complexity, within each category, a further hierarchy of complexity runs from basic to complex activities. It includes 6 items, testing the following areas: toilet use, eating, dressing, physical appearance, deambulation and bath. Scores range between 0 (excellent performance) and 30 (worst performance). (NCT01075763)
Timeframe: Baseline, Week 28 and 52
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Week 28 | Week 52 |
|---|
| Placebo | 6.40 | 7.00 | 6.87 |
,| Rebif 22 Mcg | 6.42 | 6.74 | 7.79 |
Percentage of Participants With HBV-DNA Lowering to <3,400 IU/mL and to < 2,000 IU/mL
(NCT01095835)
Timeframe: At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
| Intervention | percentage of participants (Number) |
|---|
| End of treatment: HBV-DNA < 3,400 IU/mL | 24 weeks of follow-up: HBV-DNA < 3,400 IU/mL | 48 weeks of follow-up: HBV-DNA < 3,400 IU/mL | End of treatment: HBV-DNA < 2,000 IU/mL | 24 weeks of follow-up: HBV-DNA < 2,000 IU/mL | 48 weeks of follow-up: HBV-DNA < 2,000 IU/mL |
|---|
| PEG-IFN+LAM96 | 76.0 | 24.0 | 20.0 | 72.0 | 20.0 | 20.0 |
,| PEG-IFN48 | 60.8 | 23.5 | 11.8 | 58.8 | 21.6 | 11.8 |
,| PEG-IFN96 | 67.3 | 30.8 | 30.8 | 67.3 | 28.8 | 28.8 |
Percentage of Participants With ALT Normalization
(NCT01095835)
Timeframe: At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
| Intervention | percentage of participants (Number) |
|---|
| End of treatment | 24 weeks of follow-up | 48 weeks of follow-up |
|---|
| PEG-IFN+LAM96 | 40.0 | 40.0 | 36.0 |
,| PEG-IFN48 | 35.3 | 45.1 | 35.3 |
,| PEG-IFN96 | 40.4 | 46.2 | 34.6 |
Percentage of Participants Achieving Combined Response Using a Cut-Off for HBV-DNA Levels to 2,000 IU/mL
Combined response was defined here as ALT normalization plus lowering HBV-DNA levels to a cutt-off <2,000 IU/mL. In case of missing end of treatment measurements, the next available post-treatment value was used. In case of missing week-24 post-treatment measurements, the nearest value with respect to the schedule time point in the time window 12 weeks post treatment until study end was used. Participants with missing 48 weeks follow-up measurements were considered as non-responders. However, if the scheduled 48-weeks post-treatment tests were performed earlier or later than 48 weeks post-treatment, but not earlier than 36 weeks post-treatment, the corresponding results were considered to determine response. (NCT01095835)
Timeframe: At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
| Intervention | percentage of participants (Number) |
|---|
| End of treatment | 24 weeks of follow-up | 48 weeks of follow-up |
|---|
| PEG-IFN+LAM96 | 28.0 | 20.0 | 20.0 |
,| PEG-IFN48 | 29.4 | 21.6 | 11.8 |
,| PEG-IFN96 | 38.5 | 26.9 | 23.1 |
Change From Baseline of Quantitative Hepatitis B Surface Antigen (HbsAg) Level at the End of Treatment
(NCT01095835)
Timeframe: At the end of treatment at Week 48 or 96 depending on the study arm
| Intervention | IU/mL (Mean) |
|---|
| Baseline (n=51, 51, 25) | Change from baseline (n=44, 44, 20) |
|---|
| PEG-IFN+LAM96 | 8981.0 | -3121.2 |
,| PEG-IFN48 | 9642.6 | -2801.1 |
,| PEG-IFN96 | 7229.8 | -2282.1 |
Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period
Combined response was defined as alanine aminotransferase (ALT) normalization plus lowering of hepatitis B virus (HBV) deoxyribo nucleic acid (DNA) levels to <20,000 copies/mL (<3,400 IU/mL) and was measured at the end of the 48-week follow-up period. Participants with missing 48 weeks follow-up measurements were considered as non-responders. However, if the scheduled 48-weeks post-treatment tests were performed earlier or later than 48 weeks post-treatment, but not earlier than 36 weeks post-treatment, the corresponding results were considered to determine response. (NCT01095835)
Timeframe: At the end of the 48-week follow-up period at Week 144
| Intervention | percentage of participants (Number) |
|---|
| PEG-IFN48 | 11.8 |
| PEG-IFN96 | 25.0 |
| PEG-IFN+LAM96 | 20.0 |
Percentage of Participants Achieving Histological Response
Histological response was defined as an improvement by >/= 2 in the Necroinflammatory Grading and/or by an improvement by >/= 1 score in Fibrosis Staging according to Ishak. Necroinflammatory Grading ranges 0-14 and is the combined score for necrosis, range 0-10 and inflammation, range 0-4. The participant is scored for only one inflammatory condition. A higher score indicates worse condition. Fibrosis Staging according to Ishak ranges 0-6 and a higher score indicates greater fibrosis. (NCT01095835)
Timeframe: At the end of the 48-week follow-up period at Week 144
| Intervention | percentage of participants (Number) |
|---|
| PEG-IFN48 | 13.7 |
| PEG-IFN96 | 5.8 |
| PEG-IFN+LAM96 | 8.0 |
Percentage of Participants With Lamivudine Genotype Resistance During PEG-IFN+LAM96 Combined Therapy
Lamivudine resistance mutations were assessed by detection of the following mutations: rtL80V, rtL80I, rtV173G, rtV173L, rtL180M, rtA181T, rtA181V, rtM204V, rtM204I and rtN236T. (NCT01095835)
Timeframe: At the end of the treatment period at Week 96
| Intervention | percentage of participants (Number) |
|---|
| PEG-IFN+LAM96 | 0 |
Percentage of Participants With Loss of Hepatitis B Surface Antigen (HbsAg) and Hepatitis B Surface Antibodies (Anti-HBs) Seroconversion
This outcome measure presents percentage of participants with a combined response of HBsAg < 5 IU/mL and anti-HBs positive. Positive anti-HBs represents antibodies produced against Hepatitis B Surface Antigen (HBsAg) and is an indication of recovery and immunity from HBV infection. (NCT01095835)
Timeframe: At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
| Intervention | percentage of participants (Number) |
|---|
| End of treatment | 24 weeks of follow-up | 48 weeks of follow-up |
|---|
| PEG-IFN+LAM96 | 0.0 | 0.0 | 0.0 |
,| PEG-IFN48 | 2.0 | 0.0 | 0.0 |
,| PEG-IFN96 | 3.8 | 5.8 | 7.7 |
Percentage of Participants With HBV-DNA Below Limit of Quantification
HBV-DNA limit < 6 IU/mL was defined as below quantification. (NCT01095835)
Timeframe: At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144
| Intervention | percentage of participants (Number) |
|---|
| End of treatment | 24 weeks of follow-up | 48 weeks of follow-up |
|---|
| PEG-IFN+LAM96 | 24.0 | 4.0 | 8.0 |
,| PEG-IFN48 | 17.6 | 0.0 | 2.0 |
,| PEG-IFN96 | 30.8 | 7.7 | 7.7 |
Percentage of Participants Achieving the Combined Response at the End of Treatment
Combined response was defined as ALT normalization plus lowering of HBV-DNA levels to <20,000 copies/mL (<3,400 IU/mL). In case of missing end of treatment measurements, the next available post-treatment value was used. (NCT01095835)
Timeframe: At end of treatment at Week 48 or 96 depending on the study arm
| Intervention | percentage of participants (Number) |
|---|
| PEG-IFN48 | 29.4 |
| PEG-IFN96 | 38.5 |
| PEG-IFN+LAM96 | 32.0 |
Percentage of Participants Achieving the Combined Response at 24 Weeks of Follow-up
Combined response was defined as ALT normalization plus lowering of HBV-DNA levels to <20,000 copies/mL (<3,400 IU/mL). In case of missing week-24 post-treatment measurements, the nearest value with respect to the schedule time point in the time window 12 weeks post treatment until study end was used. (NCT01095835)
Timeframe: At the end of 24 weeks of follow-up at Week 120
| Intervention | percentage of participants (Number) |
|---|
| PEG-IFN48 | 23.5 |
| PEG-IFN96 | 28.8 |
| PEG-IFN+LAM96 | 24.0 |
Number of Patients With Disease-free Survival (DFS)
DFS will be calculated from the date treatment starts to the date of documented recurrence or death. It will be summarized using the method of Kaplan and Meier. Treatment will be considered relatively ineffective in this population if the underlying 2-year DFS is <60%, whereas the combination will be considered promising if the underlying rate is >80%. (NCT01100528)
Timeframe: 5 years from time-of-enrollment
| Intervention | Participants (Count of Participants) |
|---|
| Arm I: Dacarbazine + Recombinant Interferon Alfa-2b | 8 |
Number of Participants With Toxicity or Grade 4 Adverse Events Via CTCAE Version 3.0
Number of participants with toxicity as defined as an underlying risk of >33% Grade 3 (non blood/bone marrow) or Grade 4 adverse events that are related to therapy, assessed by NCI CTCAE version 3.0 (NCT01100528)
Timeframe: up to 32 weeks from start of study
| Intervention | Participants (Count of Participants) |
|---|
| Arm I: Dacarbazine + Recombinant Interferon Alfa-2b | 2 |
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Sustained Virologic Response (SVR24)
SVR24 was defined as HCV NCT01125189)
Timeframe: Follow-up Week 24
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin | 59.2 |
| Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin | 59.6 |
| Placebo + Peg-interferon Alfa-2a + Ribavirin | 37.5 |
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died
SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. (NCT01125189)
Timeframe: From start of study treatment (day 1) up to follow-up Week 48
| Intervention | participants (Number) |
|---|
| SAEs | Discontinuations Due to AEs | Death |
|---|
| Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin | 12 | 7 | 2 |
,| Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin | 13 | 7 | 0 |
,| Placebo + Peg-interferon Alfa-2a + Ribavirin | 6 | 8 | 0 |
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Extended Rapid Virologic Response (eRVR)
eRVR was defined as HCV RNA NCT01125189)
Timeframe: Weeks 4 and 12
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin | 54.4 |
| Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin | 54.1 |
| Placebo + Peg-interferon Alfa-2a + Ribavirin | 13.9 |
Percentage of Resistant Variants Associated With Virologic Failure
"Virologic failure was defined as:~Virologic breakthrough: confirmed >1 log10 increase in hepatitis C virus (HCV) RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA NCT01125189)
Timeframe: Follow-up Week 48
| Intervention | percentage of participants (Number) |
|---|
| Virologic Breakthrough | Week 4 Futility Rule | Detectable HCV RNA at EOT | Other Criteria | Relapse |
|---|
| Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin | 8.2 | 2.0 | 7.5 | 1.4 | 18.5 |
,| Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin | 10.3 | 2.1 | 6.8 | 0.1 | 19.0 |
,| Placebo + Peg-interferon Alfa-2a + Ribavirin | 2.8 | 25.0 | 5.6 | 6.9 | 22.0 |
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Rapid Virologic Response (RVR)
RVR was defined as undetectable RNA (HCV RNA NCT01125189)
Timeframe: Week 4
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin | 59.9 |
| Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin | 56.8 |
| Placebo + Peg-interferon Alfa-2a + Ribavirin | 15.3 |
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With 12-week Sustained Virologic Response (SVR12)
SVR12 was defined as undetectable RNA (HCV RNA < lower limit of quantitation (LLOQ), target not detected (TND) at follow-up Week 12. The LLOQ was 25 IU/mL, and NCT01125189)
Timeframe: Follow-up Week 12
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin | 64.6 |
| Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin | 60.3 |
| Placebo + Peg-interferon Alfa-2a + Ribavirin | 36.1 |
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Complete Early Virologic Response (cEVR)
cEVR was defined as undetectable RNA (HCV RNA NCT01125189)
Timeframe: Week 12
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin | 77.6 |
| Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin | 75.3 |
| Placebo + Peg-interferon Alfa-2a + Ribavirin | 43.1 |
Number of Relapse-free Participants
A qualifying relapse was defined as a new or worsening neurological symptom, in the absence of fever, lasting for >= 48 hours, and accompanied by an objective change in the relevant (i.e. symptomatic) Kurtzke Functional Systems (KFS). (NCT01142466)
Timeframe: Baseline through Week 96
| Intervention | participants (Number) |
|---|
| Rebif 44 Mcg | 10 |
| No Treatment | 7 |
Time From Baseline to First Multiple Sclerosis Relapse (in Weeks)
A qualifying relapse was defined as a new or worsening neurological symptom, in the absence of fever, lasting for >= 48 hours, and accompanied by an objective change in the relevant (i.e. symptomatic) Kurtzke Functional Systems (KFS). (NCT01142466)
Timeframe: Baseline through Week 96
| Intervention | weeks (Mean) |
|---|
| Rebif 44 Mcg | 35.5 |
| No Treatment | 40.9 |
Absolute Changes in the Number of T1 Lesions From Baseline to Week 24, 48, 72 and 96
Analysis of T1 lesions was done using magnetic resonance imaging (MRI) scans. (NCT01142466)
Timeframe: Baseline to Week 24, 48, 72, and 96
| Intervention | T1 lesions (Mean) |
|---|
| Week 24 (n= 13,15) | Week 48 (n= 13,13) | Week 72 (n= 12,12) | Week 96 (n= 12,12) |
|---|
| No Treatment | -0.9 | 1.5 | -3.6 | -2.3 |
,| Rebif 44 Mcg | -0.5 | -0.8 | -0.8 | -1.8 |
Absolute Changes in the Number of T2 Lesions From Baseline to Week 24, 48, 72 and 96
Analysis of T2 lesions was done using magnetic resonance imaging (MRI) scans. (NCT01142466)
Timeframe: Baseline to Week 24, 48, 72, and 96
| Intervention | T2 lesions (Mean) |
|---|
| Week 24 (n= 13,15) | Week 48 (n= 13,13) | Week 72 (n= 12,13) | Week 96 (n= 12,12) |
|---|
| No Treatment | 1.0 | 3.2 | 3.1 | 2.1 |
,| Rebif 44 Mcg | -1.2 | 0.2 | -1.8 | -3.1 |
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. (NCT01142466)
Timeframe: Baseline to Week 96
| Intervention | participants (Number) |
|---|
| Adverse Events | Serious Adverse Events |
|---|
| No Treatment | 14 | 1 |
,| Rebif 44 Mcg | 15 | 5 |
Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. EDSS progression was defined as increase by at least 1 point if last value of EDSS was equal to 5.5, and by at least 0.5 points if last EDSS was more than 5.5. (NCT01142466)
Timeframe: Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96
| Intervention | Units on a Scale (Mean) |
|---|
| Week 12 (n= 14, 15) | Week 24 (n= 14, 15) | Week 36 (n= 13, 14) | Week 48 (n= 14, 14) | Week 60 (n= 10, 11) | Week 72 (n= 12, 13) | Week 84 (n= 12, 13) | Week 96 (n= 12, 13) |
|---|
| No Treatment | -0.1 | 0.1 | -0.2 | 0.2 | 0.0 | 0.2 | 0.2 | 0.3 |
,| Rebif 44 Mcg | -0.1 | 0.3 | 0.5 | 0.5 | 0.4 | 0.3 | 0.5 | 0.1 |
Number of Days Until First On-study Relapse
Patients were followed-up during 12 months and time to first on-study relapse from randomization was recorded. (NCT01144052)
Timeframe: 12 months
| Intervention | days (Median) |
|---|
| Natalizumab | NA |
| Interferon-beta-1b | 103 |
Proportion of Relapse Free Patients
(NCT01144052)
Timeframe: 12 months
| Intervention | participants (Number) |
|---|
| Natalizumab | 10 |
| Interferon-beta-1b | 7 |
Number of Patients With Adverse Events
Recording and reporting according to regulations. Monthly assessments or if necessary. (NCT01144052)
Timeframe: 12 months
| Intervention | participants (Number) |
|---|
| Number of patients with infections | Number of patients with injections site reactions |
|---|
| Interferon-beta-1b | 4 | 4 |
,| Natalizumab | 7 | 0 |
MRI Parameters
Number of new T2-hyperintense lesions, Number of Gd-enhancing lesions on T1-weighted images. Assessments at month 3, 6, 9, 12, 18, 24. (NCT01144052)
Timeframe: 12 months
| Intervention | Lesions (Median) |
|---|
| nT2L month 3 | nT2L month 6 | nT2L month 9 | nT2L month 12 | GD+L month 3 | GD+L month 6 | GD+L month 9 | GD+L month 12 |
|---|
| Interferon-beta-1b | 0.5 | 1.5 | 0.5 | 0 | 0 | 0 | 0 | 0 |
,| Natalizumab | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Severity of Relapses
Change of Expanded Disability Status Scale (EDSS 1-10). Higher values represent a worser outcome. (NCT01144052)
Timeframe: 12 months vs baseline
| Intervention | units on a scale (Median) |
|---|
| Natalizumab | 0 |
| Interferon-beta-1b | 0.5 |
Number of Infections
(NCT01144052)
Timeframe: 12 months
| Intervention | events (Number) |
|---|
| Natalizumab | 25 |
| Interferon-beta-1b | 8 |
Number of Participants With Relapses
(NCT01144052)
Timeframe: 12 months
| Intervention | participants (Number) |
|---|
| Natalizumab | 0 |
| Interferon-beta-1b | 2 |
Number of Relapses
(NCT01144052)
Timeframe: 12 months
| Intervention | number of events (Number) |
|---|
| Natalizumab | 0 |
| Interferon-beta-1b | 3 |
Objective Response Rate Assessed by RECIST Criteria.
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started, including baseline). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Objective response will be assessed by RECIST criteria. (NCT01158534)
Timeframe: at week 4 of cycle 2 and every other cycle thereafter
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Stable Disease | No Response |
|---|
| Celecoxib and Recombinant Interferon Alpha-2b | 0 | 3 | 5 | 9 |
Progression-free Survival
Progression-free survival measured in months and summarized using the Kaplan-Meier method. Time to objective progression will be measured from the start of treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including baseline. (NCT01158534)
Timeframe: to progression
| Intervention | months (Median) |
|---|
| Celecoxib and Recombinant Interferon Alpha-2b | 5.6 |
Overall Survival
Overall survival measured in months and summarized using the Kaplan-Meier method. (NCT01158534)
Timeframe: death
| Intervention | months (Median) |
|---|
| Celecoxib and Recombinant Interferon Alpha-2b | 14.4 |
Number of Patients With Statistically Significant Change in Cellular Immune Parameters From Baseline to 2 Months
To evaluate the effect of celecoxib and interferon alpha therapy on cellular immune parameters. Absolute change following two cycles of therapy. (NCT01158534)
Timeframe: at two months from start of treatment
| Intervention | participants (Number) |
|---|
| Celecoxib and Recombinant Interferon Alpha-2b | 0 |
Duration of Response
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, including baseline). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented. (NCT01158534)
Timeframe: end of study
| Intervention | months (Median) |
|---|
| Celecoxib and Recombinant Interferon Alpha-2b | 8.7 |
Segment 2: Complete Early Virologic Response (cEVR)
The primary efficacy endpoint for Segment 2 of the study was the percentage of participants achieving cEVR, defined as undetectable HCV RNA at Week 12. (NCT01180790)
Timeframe: Week 12
| Intervention | percentage of participants (Number) |
|---|
| Segment 2: 200 mg ACH-0141625 | 100.0 |
| Segment 2: 400 mg ACH-0141625 | 94.0 |
| Segment 2: 800 mg ACH-0141625 | 100.00 |
Segment 2: RVR4
For Segment 2, the percentage of participants in the virology population who achieved RVR4, defined as HCV RNA less than or equal to the LOQ at the Week 4 visit. (NCT01180790)
Timeframe: 4 weeks
| Intervention | percentage of participants (Number) |
|---|
| Segment 2: 200 mg ACH-0141625 | 78.9 |
| Segment 2: 400 mg ACH-0141625 | 88.8 |
| Segment 2: 800 mg ACH-0141625 | 89.5 |
Segment 1: Rapid Viral Response At Week 4 (RVR4)
The primary efficacy endpoint for Segment 1 of the study was the percentage of participants in each treatment group achieving RVR4 (hepatitis C virus [HCV] ribonucleic acid (RNA) less than or equal to the limit of quantitation [LOQ] at the Week 4 visit). (NCT01180790)
Timeframe: 4 weeks
| Intervention | percentage of participants (Number) |
|---|
| Rapid Virologic Response (%) | No Rapid Virologic Response (%) |
|---|
| Segment 1: 200 mg ACH-0141625 | 75.0 | 25.0 |
,| Segment 1: 400 mg ACH-0141625 | 75.0 | 25.0 |
,| Segment 1: 800 mg ACH-0141625 | 76.5 | 23.5 |
,| Segment 1: Placebo | 20.0 | 80.0 |
Segment 1: Safety
Segment 1: Percentage of participants with the following: adverse events, abnormal laboratory safety tests, dose reductions, interruptions, and discontinuations. Criteria for abnormal laboratory safety tests: treatment-emergent worsening Division of AIDS (Acquired Immunodeficiency Syndrome) (DAIDs) graded laboratory tests. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01180790)
Timeframe: 4 weeks
| Intervention | percentage of participants (Number) |
|---|
| Adverse Events (%) | Abnormal Laboratories (%) | Dose Reductions (%) | Dose Interruptions (%) | Dose Discontinuations (%) |
|---|
| Segment 1: 200 mg ACH-0141625 | 100.0 | 100.0 | 0 | 0 | 6.0 |
,| Segment 1: 400 mg ACH-0141625 | 93.8 | 100.0 | 0 | 0 | 0 |
,| Segment 1: 800 mg ACH-0141625 | 100.0 | 94.0 | 0 | 0 | 6.0 |
,| Segment 1: Placebo | 93.3 | 100.0 | 0 | 0 | 0 |
Segment 1: cEVR
For Segment 1, the percentage of participants in the virology population who achieved cEVR, defined as undetectable HCV RNA at Week 12. (NCT01180790)
Timeframe: 12 weeks
| Intervention | percentage of participants (Number) |
|---|
| Segment 1: 200 mg ACH-0141625 | 62.5 |
| Segment 1: 400 mg ACH-0141625 | 75.0 |
| Segment 1: 800 mg ACH-0141625 | 70.6 |
| Segment 1: Placebo | 33.3 |
Segment 2: Safety
Segment 2: Percentage of participants with the following: adverse events, abnormal laboratory safety tests and dose reductions, interruptions and discontinuations. Criteria for abnormal laboratory safety tests: treatment-emergent worsening DAIDs graded laboratory tests. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01180790)
Timeframe: 12 weeks
| Intervention | percentage of participants (Number) |
|---|
| Adverse Events (%) | Abnormal Laboratories (%) | Dose Reductions (%) | Dose Interruptions (%) | Dose Discontinuations (%) |
|---|
| Segment 2: 200 mg ACH-0141625 | 94.7 | 100.0 | 0 | 0 | 6.0 |
,| Segment 2: 400 mg ACH-0141625 | 85.0 | 95.0 | 0 | 0 | 20.0 |
,| Segment 2: 800 mg ACH-0141625 | 100.0 | 100.0 | 0 | 0 | 0 |
Segment 1 And Segment 2: End Of Treatment Response
The percentage of virology population participants who were reported as undetectable HCV RNA at the completion of treatment. (NCT01180790)
Timeframe: Week 48 (Segment 1); Week 24 (Segment 2)
| Intervention | percentage of participants (Number) |
|---|
| Segment 1: 200 mg ACH-0141625 | 75.0 |
| Segment 1: 400 mg ACH-0141625 | 75.0 |
| Segment 1: 800 mg ACH-0141625 | 64.7 |
| Segment 1: Placebo | 53.3 |
| Segment 2: 200 mg ACH-0141625 | 100.0 |
| Segment 2: 400 mg ACH-0141625 | 92.3 |
| Segment 2: 800 mg ACH-0141625 | 100.0 |
Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24)
The percentage of virology population participants who achieved SVR, defined as HCV RNA less than the LOQ, 6 months post-dosing. (NCT01180790)
Timeframe: 6 months post-dosing
| Intervention | percentage of participants (Number) |
|---|
| Segment 1: 200 mg ACH-0141625 | 62.5 |
| Segment 1: 400 mg ACH-0141625 | 56.3 |
| Segment 1: 800 mg ACH-0141625 | 35.3 |
| Segment 1: Placebo | 40.0 |
| Segment 2: 200 mg ACH-0141625 | 70.0 |
| Segment 2: 400 mg ACH-0141625 | 76.9 |
| Segment 2 : 800 mg ACH-0141625 | 83.3 |
Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12)
The percentage of virology population participants who achieved sustained virologic response (SVR), defined as HCV RNA less than the LOQ, at 12 weeks (3 months) post-dosing. (NCT01180790)
Timeframe: 3 months post-dosing
| Intervention | percentage of participants (Number) |
|---|
| Segment 1: 200 mg ACH-0141625 | 56.3 |
| Segment 1: 400 mg ACH-0141625 | 56.3 |
| Segment 1: 800 mg ACH-0141625 | 35.3 |
| Segment 1: Placebo | 40.0 |
| Segment 2: 200 mg ACH-0141625 | 80.0 |
| Segment 2: 400 mg ACH-0141625 | 76.9 |
| Segment 2: 800 mg ACH-0141625 | 84.5 |
Segment 1 And Segment 2: HCV RNA Change From Baseline
The mean change from baseline in log10 HCV RNA level by visit for the virology population (NCT01180790)
Timeframe: Week 4
| Intervention | log10 HCV RNA Level (Mean) |
|---|
| Segment 1: 200 mg ACH-0141625 | -4.94 |
| Segment 1: 400 mg ACH-0141625 | -4.60 |
| Segment 1: 800 mg ACH-0141625 | -4.94 |
| Segment 1: Placebo | -2.22 |
| Segment 2: 200 mg ACH-0141625 | -4.74 |
| Segment 2: 400 mg ACH-0141625 | -5.04 |
| Segment 2: 800 mg ACH-0141625 | -4.51 |
Segment 1 And Segment 2: HCV RNA Change From Baseline
Change from baseline in log10 HCV RNA level by visit. (NCT01180790)
Timeframe: Week 12
| Intervention | log10 HCV RNA level (Mean) |
|---|
| Segment 1: 200 mg ACH-0141625 | -5.13 |
| Segment 1: 400 mg ACH-0141625 | -4.51 |
| Segment 1: 800 mg ACH-0141625 | -4.67 |
| Segment 1: Placebo | -3.48 |
| Segment 2: 200 mg ACH-0141625 | -4.90 |
| Segment 2: 400 mg ACH-0141625 | -5.08 |
| Segment 2: 800 mg ACH-0141625 | -4.58 |
Number of Participants With Adverse Events
Adverse events determined and evaluated by patient reporting and the DAIDS toxicity table. (NCT01185028)
Timeframe: 1 year and 2 months
| Intervention | participants (Number) |
|---|
| Nitazoxanide With Pegylated Interferon And Ribavirin | 8 |
Sustained Viral Response Rate
Proportion of participants that are HCV negative 6 months after treatment completion (NCT01185028)
Timeframe: 1 year and 2 mos
| Intervention | participants (Number) |
|---|
| Nitazoxanide With Pegylated Interferon And Ribavirin | 8 |
Tolerability of Study Drug Measured as Discontinuation.
Proportion of individuals that discontinued study drug due to intolerability. (NCT01185028)
Timeframe: 1 year and 2 mos
| Intervention | Participants (Count of Participants) |
|---|
| Nitazoxanide With Pegylated Interferon And Ribavirin | 0 |
HCV RNA Result
Will measure mean HCV RNA levels 4 weeks after liver transplant (NCT01192698)
Timeframe: 4 weeks after liver transplant
| Intervention | IU/ml (Mean) |
|---|
| IV Interferon | 924,082 |
| no Treatment | 3,731,749 |
Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L)
The EQ-5D health questionnaire is a generic self-reported health-related quality of life instrument that includes a 100 mm Visual Analog Scale (VAS) to measure the general health state, as well as 5 items corresponding to one dimension each: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In this study, the VAS scale is not collected and the version 3L of the scale was used: Each dimension had 3 possible levels: 1 = no problem, 2 = some problems and 3 = extreme problems. EQ-5D-3L weighted health state index exists that combines the score of the 5 dimensions and ranges from 0 to 1 (full health). The variables for the 5 dimensions of the EQ-5D descriptive system was named 'mobility','selfcare', 'activity', 'pain', and 'anxiety'. The 5 variables contained the values for the different dimensions in the EQ-5D health profile (i.e. 1, 2, or 3). (NCT01198132)
Timeframe: 2 years post treatment (IMP) administration
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n=60, 63) | Change at Week 96 (n=43, 45) |
|---|
| Cholecalciferol | 0.7834 | -0.0051 |
,| Placebo | 0.7937 | 0.0043 |
Number of Relapse-Free (Documented) Subjects
The relapse-free patients after 2 years of treatment was calculated using Cochran-Mantel-Haenszel test using the site as control variable. (NCT01198132)
Timeframe: 2 years post treatment (IMP) administration
| Intervention | subjects (Number) |
|---|
| Cholecalciferol | 35 |
| Placebo | 27 |
Mean Number of Relapses Per Subject
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Mean and standard deviation were reported. (NCT01198132)
Timeframe: 2 years post treatment (IMP) administration
| Intervention | relapses (Mean) |
|---|
| Cholecalciferol | 0.5 |
| Placebo | 0.5 |
Cumulative Probability of Progression of Disability (Kaplan-Meier Curves)
Disability progression was assessed using Expanded disability status scale (EDSS). EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. A one-point increase on the EDSS scale was considered as a progression in disability. The time to disability progression was summarized using Kaplan-Meier survival methods. The cumulative probability of confirmed disease progression at each visit was obtained by applying a Kaplan-Meier method to the time to confirmed disease progression. (NCT01198132)
Timeframe: Baseline up to week 96
| Intervention | percentage of subjects (Number) |
|---|
| Cholecalciferol | 12.7 |
| Placebo | 9.1 |
Annualized Relapse Rate
The annualized relapse rate was calculated for each treatment group as follows: the number of relapses observed during the study period divided by the time spent in the study (in years). (NCT01198132)
Timeframe: 2 years post treatment (IMP) administration
| Intervention | Relapse per year (Mean) |
|---|
| Cholecalciferol | 0.45 |
| Placebo | 0.34 |
Time to First Documented Relapse
Time to First Documented Relapse was calculated using Kaplan-Meier survival methods. (NCT01198132)
Timeframe: 2 years post treatment (IMP) administration
| Intervention | weeks (Median) |
|---|
| Cholecalciferol | NA |
| Rebif +Placebo | NA |
Number of New or Extended Lesions by T1- and T2-Weighted Magnetic Resonance Imaging (MRI)
(NCT01198132)
Timeframe: 2 years post treatment (IMP) administration
| Intervention | lesions (Mean) |
|---|
| T1-weighted MRI | T2-weighted MRI |
|---|
| Cholecalciferol | 0.4 | 0.5 |
,| Placebo | 1.9 | 2.0 |
Changes From Baseline in Measured Lesion Load (T2)
Baseline defined as last value recorded prior to first intake of study drug. (NCT01198132)
Timeframe: Baseline, Week 96
| Intervention | cubic millimeter (mm^3) (Mean) |
|---|
| Baseline (n=49, 43) | Change at Week 96 (n=44, 38) |
|---|
| Cholecalciferol | 5305.4 | -315.0 |
,| Placebo | 3520.1 | 596.3 |
Change From Baseline in Measurement and Evaluation of Cognitive Ability by Paced Auditory Serial Addition Task (PASAT) Total Score At Week 96
The Adapted Paced Auditory Serial Addition Task (PASAT) is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. The total score for PASAT is the total number of correct answers (out of 60, for a total possible score ranging from 0-60 with higher score indicates higher auditory processing speed) for each trial. Change from baseline in PASAT total score at Week 96 was summarized. (NCT01198132)
Timeframe: Baseline, Week 96
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change at Week 96 |
|---|
| Cholecalciferol | 39.9 | 6.4 |
,| Placebo | 43.3 | 6.0 |
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Abnormal Clinical Laboratory
A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect and TEAE was defined as newly occurring or worsening after first dose. Clinical laboratory abnormalities are expected to be reported as adverse events if they met any criterion for seriousness, led to treatment discontinuation, required a medical intervention or were considered clinically significant by the investigator. (NCT01198132)
Timeframe: Baseline up to end of treatment (week 96)
| Intervention | subjects (Number) |
|---|
| TEAEs | Serious TEAEs |
|---|
| Cholecalciferol | 43 | 11 |
,| Placebo | 35 | 10 |
Change From Baseline in Emotional Dyscontrol Sub-score of the EHD Scale at Month 18
EHD scale is a tool to assess the depressive mood dimensions 'lack of emotional control' (emotional dyscontrol) and 'blunted effect' which comprises of 11 items graded in 4 degrees from 1 (not at all) to 4 (very much), where 4 corresponds to the worst state. The emotional dyscontrol sub-score is the sum of items 1, 2, 4, 5, 9, 10, and 11. The total possible score range from 1 (not at all) to 28 (very much), where 28 corresponds to worst state. (Radat F et al., 2007) (NCT01201343)
Timeframe: Baseline and Month 18
| Intervention | units on a scale (Mean) |
|---|
| Interferon-beta | -0.6 |
Change From Baseline in Emotional Dyscontrol Sub-score of the EHD Scale at Month 24
EHD scale is a tool to assess the depressive mood dimensions 'lack of emotional control' (emotional dyscontrol) and 'blunted effect' which comprises of 11 items graded in 4 degrees from 1 (not at all) to 4 (very much), where 4 corresponds to the worst state. The emotional dyscontrol sub-score is the sum of items 1, 2, 4, 5, 9, 10, and 11. The total possible score range from 1 (not at all) to 28 (very much), where 28 corresponds to worst state. (Radat F et al., 2007) (NCT01201343)
Timeframe: Baseline and Month 24
| Intervention | units on a scale (Mean) |
|---|
| Interferon-beta | -0.1 |
Change From Baseline in Center for Epidemiologic Studies Depression (CES-D) Score at Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24
CES-D is an auto-questionnaire including 20 items to screen for depressive feelings and behaviour. The 20 items of this scale are graded from 0 (never) to 3 (always), where 3 corresponds to the most severe state with the exception of items 4, 8, 12 and 16 (scoring was reversed before the calculation of the total score). Total score ranged from 0 (never) to 60 (always), where 60 corresponds to most severe state. (Radloff LS, 1977) (NCT01201343)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n= 70) | Change at Month 1 (n= 65) | Change at Month 2 (n= 62) | Change at Month 3 (n= 64) | Change at Month 4 (n= 58) | Change at Month 5 (n= 58) | Change at Month 6 (n= 56) | Change at Month 9 (n= 58) | Change at Month 12 (n= 57) | Change at Month 18 (n= 61) | Change at Month 24 (n= 63) |
|---|
| Interferon-beta | 13.5 | 1.0 | 1.5 | -0.5 | -1.0 | -1.1 | 0.9 | 0.9 | 1.6 | -0.2 | 0.1 |
Change From Baseline in Center for State-trait Anger Expression Inventory 2 (STAXI-state) Score at Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24
STAXI-state scale measures the intensity of anger as an emotional state (state anger) and the disposition to experience angry feelings as a personality trait (trait anger). In this study only 1 of the original 6 scales was used, the state anger scale, which measures the intensity of anger at a given moment as emotional state. This scale consists of 15 items graded in 4 degrees from 1 (not at all) to 4 (very much), where 4 corresponds to the worst state. The total score range from 1 (not at all) to 60 (very much), where 60 corresponds to the worst state. (Spielberger CD, 1996) (NCT01201343)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n= 70) | Change at Month 1 (n= 65) | Change at Month 2 (n= 62) | Change at Month 3 (n= 64) | Change at Month 4 (n= 59) | Change at Month 5 (n= 58) | Change at Month 6 (n= 56) | Change at Month 9 (n= 58) | Change at Month 12 (n= 57) | Change at Month 18 (n= 61) | Change at Month 24 (n= 63) |
|---|
| Interferon-beta | 16.8 | 0.0 | 1.0 | -0.0 | -0.3 | -0.0 | 1.1 | 1.1 | 0.9 | 0.8 | 1.0 |
Change From Baseline in Emotional Abrasion Sub-score of the EHD Scale at Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24
EHD scale is a tool to assess the depressive mood dimensions 'lack of emotional control' (emotional dyscontrol) and 'blunted effect' which comprises of 11 items graded in 4 degrees from 1 (not at all) to 4 (very much), where 4 corresponds to the worst state. The emotional abrasion sub-score is the sum of items 3, 6, 7, and 8. The total possible score range from 1 (not at all) to 16 (very much), where 16 corresponds to worst state. (Radat F et al., 2007) (NCT01201343)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n= 70) | Change at Month 1 (n= 64) | Change at Month 2 (n= 62) | Change at Month 3 (n= 64) | Change at Month 4 (n= 59) | Change at Month 5 (n= 58) | Change at Month 6 (n= 56) | Change at Month 9 (n= 58) | Change at Month 12 (n= 57) | Change at Month 18 (n= 61) | Change at Month 24 (n= 63) |
|---|
| Interferon-beta | 5.6 | 0.3 | -0.1 | -0.0 | -0.0 | -0.2 | -0.3 | -0.1 | -0.0 | -0.3 | -0.3 |
Change From Baseline in Emotional Dyscontrol Sub-score of the Depressive Mood Scale (Echelle d'Humeur Depressive [EHD]) Scale at Month 12
EHD scale is a tool to assess the depressive mood dimensions 'lack of emotional control' (emotional dyscontrol) and 'blunted effect' which comprises of 11 items graded in 4 degrees from 1 (not at all) to 4 (very much), where 4 corresponds to the worst state. The emotional dyscontrol sub-score is the sum of items 1, 2, 4, 5, 9, 10, and 11. The total possible score range from 1 (not at all) to 28 (very much), where 28 corresponds to worst state. (Radat F et al., 2007) (NCT01201343)
Timeframe: Baseline and Month 12
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n= 70) | Change at Month 12 (n= 57) |
|---|
| Interferon-beta | 12.7 | -0.5 |
Change From Baseline in Fatigue Score at Months 1, 2, 3, 6, 12 and 24
Fatigue scale was derived from the United Kingdom Neurological Disability Scale (UKNDS), and evaluates fatigue according to the participant's subjective impression and the functional disability that it causes. 'Yes' or 'No' answers result in a score that ranges from 0 to 5, where a score 5 shows worse state. (Sharrack B et al., 1999) (NCT01201343)
Timeframe: Baseline, Months 1, 2, 3, 6, 12, and 24
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n= 62) | Change at Month 1 (n= 58) | Change at Month 2 (n= 55) | Change at Month 3 (n= 56) | Change at Month 6 (n= 50) | Change at Month 12 (n= 49) | Change at Month 24 (n= 56) |
|---|
| Interferon-beta | 2.1 | 0.5 | 0.4 | 0.2 | 0.4 | 0.1 | -0.1 |
Change From Baseline in State-trait Anxiety Inventory (STAI State) Score at Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24
STAI state scale is an auto-evaluation scale for anxiety. This scale includes 20 items that allow quantifying feeling of apprehension, tension, nervousness and worry that the participant feels at the time of the completion of the questionnaire. The 20 items are graded from 1 (no) to 4 (yes), where 'yes' corresponds to the best state for items 1, 2, 5, 8, 10, 11, 15, 16, 19, 20 (scoring was reversed before calculation of total score); and to the worst state for items 3, 4, 6, 7, 9, 12, 13, 14, 17, 18. The total score ranged from 1 (best state) to 80 (worst state). (Spielberger CD et al., 1983) (NCT01201343)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6, 9, 12, 18 and 24
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n= 70) | Change at Month 1 (n= 65) | Change at Month 2 (n= 62) | Change at Month 3 (n= 64) | Change at Month 4 (n= 59) | Change at Month 5 (n= 58) | Change at Month 6 (n= 55) | Change at Month 9 (n= 58) | Change at Month 12 (n= 57) | Change at Month 18 (n= 61) | Change at Month 24 (n= 63) |
|---|
| Interferon-beta | 35.9 | 0.8 | 0.3 | -1.7 | -1.5 | -0.8 | -1.4 | -0.2 | -0.3 | -1.2 | -1.4 |
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After the Last Planned Dose of Study Drugs (SVR12 Planned)
The table below shows the percentage of participants achieving Sustained Virologic Response 12 weeks after last planned dose of study medication (SVR12 planned). SVR was defined as having Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 international units/milliliter (IU/mL). (NCT01241760)
Timeframe: End of trial, 12 weeks after last planned dose
| Intervention | percentage of participants with response (Number) |
|---|
| T12(q8h)/PR | 72.8 |
| T12(b.i.d.)/PR | 74.3 |
Percentage of Participants With On-treatment Virologic Failure Which Required Them to Permanently Discontinue All Study Drugs
The table below shows the percentage of participants who met a stopping rule, defined as having a hepatitis C virus (HCV) ribonucleic acid (RNA) value at Week 4 >1000 IU/mL and at Weeks 12, 24, 32 and 40 ≥25 IU/mL. (NCT01241760)
Timeframe: Week 4, 12, 24, 32, 40
| Intervention | percentage of participants (Number) |
|---|
| T12(q8h)/PR | 9.7 |
| T12(b.i.d.)/PR | 10.3 |
Percentage of Participants Who Relapsed During Follow-up Period
The table below shows the percentage of participants who relapsed (ie, those having confirmed detectable hepatitis C virus [HCV] ribonucleic acid [RNA] during the 12-week follow-up period after previous HCV RNA <25 IU/mL, target not detected, at end of treatment). (NCT01241760)
Timeframe: During Follow-Up (24 weeks after the last dose of study drug)
| Intervention | percentage of participants (Number) |
|---|
| T12(q8h)/PR | 7.2 |
| T12(b.i.d.)/PR | 7.7 |
Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points.
The table below shows the percentage of participants with undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels, which means less than 25 IU/ml, target not detected, at different time points during the study. (NCT01241760)
Timeframe: Baseline, Week 4 and Week 4+12.
| Intervention | percentage of participants with response (Number) |
|---|
| Baseline | at Week 4 | at Week 4 and Week 12 |
|---|
| T12(b.i.d.)/PR | 0 | 69.4 | 66.1 |
,| T12(q8h)/PR | 0 | 67.4 | 63.1 |
Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned)
The table below shows the effect of interleukin 28B (IL28B) gene's subtype (CC, CT or TT genotype) on the primary outcome measure: SVR12 planned. (NCT01241760)
Timeframe: End of trial, 12 weeks after the last planned dose
| Intervention | percentage of participants with response (Number) |
|---|
| CC genotype (n = 108; n = 103) | CT genotype (n = 207; n = 207) | TT genotype (n = 56; n = 59) |
|---|
| T12(b.i.d.)/PR | 92.4 | 67.5 | 65.5 |
,| T12(q8h)/PR | 86.8 | 67.8 | 64.9 |
Percentage of Participants With Sustained Virologic Response 72 Weeks After the Start of Study Medication (SVR72 Planned)
The table below shows the percentage of participants achieving SVR 72 weeks after the start of study medication (SVR72 planned). SVR was defined as having plasma Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 IU/mL, target not detected, at end of treatment and up to 72 weeks after start of study medication (i.e., no confirmed detectable HCV RNA in between). (NCT01241760)
Timeframe: End of trial, 72 weeks after the start of study medication
| Intervention | percentage of participants with response (Number) |
|---|
| T12(q8h)/PR | 69.0 |
| T12(b.i.d.)/PR | 70.2 |
Percentage of Participants With Sustained Virologic Response 24 Weeks After the Last Planned Dose of Study Drugs (SVR24 Planned)
The table below shows the percentage of participants achieving SVR 24 weeks after the last planned dose of study medication. SVR was defined as having Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 international units/milliliter (IU/mL). The response for T12(b.i.d)/PR group is higher than that after 12 weeks because HCV RNA data for two participants were missing for SVR assessment at that time. Consequently, by definition of SVR12, they were counted as not having achieved SVR12. (NCT01241760)
Timeframe: End of trial, 24 weeks after last planned dose
| Intervention | percentage of participants with response (Number) |
|---|
| T12(q8h)/PR | 72.8 |
| T12(b.i.d.)/PR | 74.8 |
Number of T1 Hypointense Lesions During the Double-Blind Treatment
The total number of new T1-Hypo-Intense Lesions (Chronic Black Holes) for all participants in the treatment group was calculated as the sum of the individual number of new lesions at Weeks 24, 48, and 96. (NCT01247324)
Timeframe: Baseline up to Week 96
| Intervention | lesions (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 1307 |
| Ocrelizumab | 564 |
Number of Participants With Adverse Events (AEs)
AEs included infusion related reactions (IRRs) and serious MS relapses, but excluded non-serious MS relapses. Serious Adverse Events (SAEs) included serious MS relapses and serious IRRs. (NCT01247324)
Timeframe: Baseline up to Week 96
| Intervention | Participants (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 331 |
| Ocrelizumab | 327 |
Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double Blind Treatment
The total number of new and/or enlarging T2 lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96. (NCT01247324)
Timeframe: Baseline up to Week 96
| Intervention | lesions (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 1916 |
| Ocrelizumab | 430 |
Exposure to Ocrelizumab (Area Under the Concentration - Time Curve, AUC)
AUC represents total drug exposure for one dosing interval after the 4th dose. (NCT01247324)
Timeframe: Pre-infusion at Weeks 1, 24, 48, 72; and 30 minutes post-infusion at Week 72; at any time during Weeks 84 and 96
| Intervention | micrograms per milliliter*day (Mean) |
|---|
| Ocrelizumab | 3513 |
Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks
ARR was protocol-defined and calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of exposure to that treatment. (NCT01247324)
Timeframe: Week 96
| Intervention | relapses/participant year of treatment (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 0.292 |
| Ocrelizumab | 0.156 |
Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96
"Brain volume was recorded as an absolute normalized value at the baseline visit then recorded at subsequent visits as a percentage change relative to the absolute value at the baseline visit. Therefore, brain volume at Week 24 was calculated as the brain volume at the baseline visit multiplied by 1 + ([percentage change in brain volume from baseline visit to Week 24]/100). Estimates are from analysis based on mixed-effect model of repeated measures (MMRM) using unstructured covariance matrix: Percentage Change = Brain Volume at Week 24 + Geographical Region (US vs. ROW) + Baseline EDSS (< 4.0 vs. >= 4.0) + Week + Treatment + Treatment*Week (repeated values over Week) + Brain Volume at Week 24*Week." (NCT01247324)
Timeframe: From Week 24 up to Week 96
| Intervention | percent change (Mean) |
|---|
| Interferon Beta-1a 44 mcg SC | -0.741 |
| Ocrelizumab | -0.572 |
Number of T1 Gadolinium (Gd)-Enhancing Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double-Blind Treatment
The total number of T1 gadolinium-enhancing lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96. (NCT01247324)
Timeframe: Baseline up to Week 96
| Intervention | lesions (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 337 |
| Ocrelizumab | 21 |
Percentage of Participants Who Have No Evidence of Disease Activity (NEDA) up to Week 96
NEDA was defined only for participants with a baseline EDSS score >=2.0. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). Participants who completed the 96- week treatment period were considered as having evidence of disease activity if at least one protocol- defined relapse (PDR), a confirmed disability progression (CDP) event or at least one MRI scan showing MRI activity (defined as Gd-enhancing T1 lesions, or new or enlarging T2 lesions) was reported during the 96-week treatment period, otherwise the participant was considered as having NEDA. (NCT01247324)
Timeframe: Week 96
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 27.1 |
| Ocrelizumab | 47.4 |
Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks
Disability improvement was assessed only for the subgroup of participants with a baseline EDSS score of >= 2.0. It was defined as a reduction in EDSS score of: A) >=1.0 from the baseline EDSS score when the baseline score was >=2 and <=5.5 B) >= 0.5 when the baseline EDSS score > 5.5. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. (NCT01247324)
Timeframe: Week 96
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 12.42 |
| Ocrelizumab | 20.00 |
Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks During the Double-Blind Treatment Period
Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) >=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (<=) 5.5 B) >=0.5 point from the baseline EDSS score when the baseline score was >5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment. (NCT01247324)
Timeframe: Week 108
| Intervention | weeks (Median) |
|---|
| Interferon Beta-1a 44 mcg SC | NA |
| Ocrelizumab | NA |
Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks During the Double-Blind Treatment Period
Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) >=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (<=) 5.5 B) >=0.5 point from the baseline EDSS score when the baseline score was >5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 24 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment. (NCT01247324)
Timeframe: Week 108
| Intervention | weeks (Median) |
|---|
| Interferon Beta-1a 44 mcg SC | NA |
| Ocrelizumab | NA |
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score to Week 96
MSFC score consists of: A) Timed 25-Foot walk; B) 9-Hole Peg Test (9-HPT); and C) Paced Auditory Serial Addition Test (PASAT-3 version). The MSFCS is based on the concept that scores for these three dimensions (arm, leg, and cognitive function) are combined to create a single score (the MSFC) that can be used to detect change over time in a group of participants with MS. Since the three primary measures differ in what they actually measure, a common composite score for the three different measures i.e., Z- score was selected for the purpose. MSFC Score = {Z arm, average + Z leg, average + Z cognitive} / 3.0. The results from each of these three tests are transformed into Z-scores and averaged to yield a composite score for each participant at each time point. A score of +1 indicates that, on average, an individual scored 1 standard deviation (SD) better than the reference population and a score of -1 indicates that an individual scored 1 SD worse than the reference population. (NCT01247324)
Timeframe: Baseline, Week 96
| Intervention | Z-score (Mean) |
|---|
| Unadjusted Baseline mean (n= 359, 360) | Adjusted Week 96 mean (n= 308, 322) |
|---|
| Interferon Beta-1a 44 mcg SC | 0.028 | 0.174 |
,| Ocrelizumab | -0.012 | 0.213 |
Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab
Number of participants positive for anti-drug antibodies (ADAs) to ocrelizumab is the number of post- baseline evaluable participants determined to have treatment-induced ADA or treatment-enhanced ADA during the study period. (NCT01247324)
Timeframe: Baseline up to week 96
| Intervention | Participants (Number) |
|---|
| Positive sample at baseline (n= 397, 396) | Positive for ADA post-baseline (n= 401, 402) |
|---|
| Interferon Beta-1a 44 mcg SC | 2 | 2 |
,| Ocrelizumab | 1 | 1 |
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA)
PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review. Hepatic parameters thresholds were defined as follows: Alanine Aminotransferase (ALT) >3, 5 or 10 Upper Limit of Normal (ULN); Aspartate Aminotransferase (AST) >3, 5 or 10 ULN; Alkaline Phosphatase >1.5 ULN; Total Bilirubin (TB) >1.5 ULN; and ALT >3 ULN and TB >2 ULN. (NCT01252355)
Timeframe: First study drug intake up to 28 days after last study drug intake, for up to 112 weeks
| Intervention | participants (Number) |
|---|
| ALT >3 ULN | ALT >5 ULN | ALT >10 ULN | AST >3 ULN | AST >5 ULN | AST >10 ULN | Alkaline Phosphatase >1.5 ULN | TB >1.5 ULN | ALT >3 ULN and TB >2 ULN |
|---|
| Placebo + IFN-beta | 6 | 1 | 1 | 3 | 2 | 1 | 0 | 2 | 0 |
,| Teriflunomide 14 mg + IFN-beta | 9 | 5 | 2 | 4 | 3 | 0 | 0 | 2 | 0 |
,| Teriflunomide 7 mg + IFN-beta | 9 | 6 | 3 | 4 | 3 | 2 | 2 | 0 | 0 |
Time to Relapse: Kaplan-Meier Estimates of the Probability of no Relapse at Week 24, 48, and 72
Probability of no relapse at 24, 48 and 72 weeks was estimated using Kaplan-Meier method on the time to relapse defined as the time from randomization to first EDSS confirmed relapse. Participants free of confirmed relapse (no EDSS confirmed relapse observed on treatment) were censored at the date of the last study drug intake. Kaplan-Meier method consists in computing probabilities of non-occurrence of event at any observed time of event and multiplying successive probabilities for time <=t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. (NCT01252355)
Timeframe: Up to a maximum of 108 weeks depending on time of enrollment
| Intervention | percent probability of no relapse (Number) |
|---|
| Percent probability of no relapse at Week 24 | Percent probability of no relapse at Week 48 | Percent probability of no relapse at Week 72 |
|---|
| Placebo + IFN-beta | 81.9 | 67.3 | 58.3 |
,| Teriflunomide 14 mg + IFN-beta | 87.1 | 80.8 | 73.1 |
,| Teriflunomide 7 mg + IFN-beta | 86.8 | 80.6 | 78.2 |
Brain MRI Assessment: Volume of Gd-enhancing T1-lesions Per MRI Scan
Total volume of Gd-enhancing T1-lesions per scan is the sum of the volumes of Gd-enhancing T1-lesions observed during the treatment period divided by the total number of scans performed during the treatment period. (NCT01252355)
Timeframe: Up to a maximum of 108 weeks depending on time of enrollment
| Intervention | milliliters per scan (Number) |
|---|
| Placebo + IFN-beta | 0.045 |
| Teriflunomide 7 mg + IFN-beta | 0.009 |
| Teriflunomide 14 mg + IFN-beta | 0.01 |
Brain MRI Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) at Week 24
The total lesion volume (burden of disease) is the total volumes of hyperintense on T2 plus hypointense on T1 as measured by MRI scan. Least-square means were estimated using a Mixed-effect model with repeated measures (MMRM) on cubic root transformed volume data with factors for treatment, region, IFN-beta dose stratum, visit, treatment-by-visit interaction, cubic root transformed baseline burden of disease, and baseline-by-visit interaction. (NCT01252355)
Timeframe: Baseline, Week 24
| Intervention | milliliter (Least Squares Mean) |
|---|
| Placebo + IFN-beta | -0.008 |
| Teriflunomide 7 mg + IFN-beta | -0.011 |
| Teriflunomide 14 mg + IFN-beta | -0.044 |
Overview of Adverse Events (AEs)
AEs are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. (NCT01252355)
Timeframe: First study drug intake up to 28 days after last study drug intake, for up to 112 weeks
| Intervention | participants (Number) |
|---|
| Any AE | Any Serious AE | Any AE Leading to Death | Any AE Leading to Study Drug Discontinuation |
|---|
| Placebo + IFN-beta | 119 | 8 | 0 | 9 |
,| Teriflunomide 14 mg + IFN-beta | 140 | 14 | 0 | 22 |
,| Teriflunomide 7 mg + IFN-beta | 140 | 13 | 0 | 16 |
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per Scan (Poisson Regression Estimates)
Number of Gd-enhancing T1-lesions per scan is the total number of Gd-enhancing T1-lesions that occurred during the treatment period divided by the total number of scans performed during the treatment period. To account for the different number of scans among participants, a Poisson regression model with robust error variance was used (total number of Gd-enhancing T1-lesions as response variable; log-transformed number of scans as offset variable; treatment group, region of enrollment, IFN-beta dose stratum and baseline number of Gd-enhancing T1-lesions as covariates). (NCT01252355)
Timeframe: Up to a maximum of 108 weeks depending on time of enrollment
| Intervention | lesions per scan (Number) |
|---|
| Placebo + IFN-beta | 0.542 |
| Teriflunomide 7 mg + IFN-beta | 0.257 |
| Teriflunomide 14 mg + IFN-beta | 0.158 |
Annualized Relapse Rate (ARR) (Poisson Regression Estimates)
"ARR is the total number of confirmed relapses that occurred during the treatment period divided by the total number of patient-years treated. Each episode of relapse (appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever) was to be confirmed by an increase in Expanded Disability Status Scale (EDSS) score or Functional System scores. To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as offset variable; treatment group, region of enrollment and IFN-beta dose stratum, and number of relapses in the year prior to randomization as covariates)." (NCT01252355)
Timeframe: Up to a maximum of 108 weeks depending on time of enrollment
| Intervention | relapses per patient-year (Number) |
|---|
| Placebo + IFN-beta | 0.298 |
| Teriflunomide 7 mg + IFN-beta | 0.242 |
| Teriflunomide 14 mg + IFN-beta | 0.238 |
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 3
SVR24 was defined as undetectable HCV RNA (HCV RNA NCT01257204)
Timeframe: Follow-up Week 24
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir, 60 mg, 12-Week Cohort | 69.2 |
| Daclatasvir, 60 mg, 16-Week Cohort | 66.7 |
| Placebo | 59.3 |
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 3
SVR12 was defined as undetectable HCV RNA (HCV RNA NCT01257204)
Timeframe: Follow-up Week 12
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir, 60 mg, 12-Week Cohort | 69.2 |
| Daclatasvir, 60 mg, 16-Week Cohort | 77.8 |
| Placebo | 51.9 |
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. (NCT01257204)
Timeframe: From end of treatment period up to Week 48 (follow-up period)
| Intervention | participants (Number) |
|---|
| AEs | SAEs | Deaths |
|---|
| Daclatasvir, 60 mg, 12-Week Cohort: Follow-up | 16 | 2 | 0 |
,| Daclatasvir, 60 mg, 16-Week Cohort: Follow-up | 12 | 0 | 0 |
,| Placebo: Follow-up | 11 | 0 | 0 |
Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2
"Virologic failure was defined as:~Virologic breakthrough: confirmed >1 log10 increase in HCV RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA NCT01257204)
Timeframe: Baseline up to Week 48
| Intervention | participants (Number) |
|---|
| Virologic breakthrough (n=24,23,24) | <1 log10 decrease in HCV RNA at Week4 (n=24,23,24) | HCV RNA ≥LLOQ or | Relapse (n=23,21,22) | |
|---|
| Daclatasvir, 60 mg, 12-Week Cohort | 0 | 0 | 1 | 1 |
,| Daclatasvir, 60 mg, 16-Week Cohort | 1 | 1 | 2 | 0 |
,| Placebo | 1 | 0 | 1 | 2 |
Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3
"Virologic failure was defined as:~Virologic breakthrough: confirmed >1 log10 increase in HCV RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA NCT01257204)
Timeframe: Baseline up to Week 48
| Intervention | participants (Number) |
|---|
| Virologic breakthrough (n=26,27,27) | <1 log10 decrease in HCV RNA at Week4 (n=26,27,27) | HCV RNA ≥LLOQ or | Relapse (n=25,24,21) | |
|---|
| Daclatasvir, 60 mg, 12-Week Cohort | 0 | 0 | 1 | 6 |
,| Daclatasvir, 60 mg, 16-Week Cohort | 0 | 1 | 2 | 6 |
,| Placebo | 1 | 3 | 3 | 3 |
Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 2
cEVR was defined as undetectable HCV RNA (HCV RNA NCT01257204)
Timeframe: Week 12
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir, 60 mg, 12-Week Cohort | 91.7 |
| Daclatasvir, 60 mg, 16-Week Cohort | 82.6 |
| Placebo | 75.0 |
Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 3
cEVR was defined as undetectable HCV RNA (HCV RNA NCT01257204)
Timeframe: Week 12
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir, 60 mg, 12-Week Cohort | 80.8 |
| Dacalatasvir, 60 mg, 16-Week Cohort | 88.9 |
| Placebo | 59.3 |
Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 2
RVR was defined as undetectable HCV RNA (HCV RNA NCT01257204)
Timeframe: Week 4
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir, 60 mg, 12-Week Cohort | 87.5 |
| Daclatasvir, 60 mg, 16-Week Cohort | 73.9 |
| Placebo | 41.7 |
Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 3
RVR was defined as undetectable HCV RNA (HCV RNA NCT01257204)
Timeframe: Week 4
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir, 60 mg, 12-Week Cohort | 84.6 |
| Daclatasvir, 60 mg, 16-Week Cohort | 74.1 |
| Placebo | 37.0 |
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 2
SVR12 was defined as undetectable HCV RNA (HCV RNA NCT01257204)
Timeframe: Follow-up Week 12
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir, 60 mg, 12-Week Cohort | 87.5 |
| Daclatasvir, 60 mg, 16-Week Cohort | 82.6 |
| Placebo | 70.8 |
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 2
SVR24 was defined as undetectable HCV RNA (HCV RNA NCT01257204)
Timeframe: Follow-up Week 24
| Intervention | percentage of participants (Number) |
|---|
| Daclatasvir, 60 mg, 12-Week Cohort | 83.3 |
| Daclatasvir, 60 mg, 16-Week Cohort | 82.6 |
| Placebo | 62.5 |
Change in the Total Symptom Score (TSS)
Change in the Total Symptom Score which assessed improvement in disease symptoms measured by the change in TSS from the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) instrument being used in this study from baseline to 12 months. This 19 item instrument includes the previously validated 9 item brief fatigue inventory (BFI), symptoms related to splenomegaly, inactivity, cough, night sweats, pruritus, bone pains, fevers, weight loss, and an overall quality of life assessment. Each item is scored from 0-10 with full scale from 0-190, with higher scores mean worse symptoms. (NCT01259856)
Timeframe: baseline and 12 months
| Intervention | score on a scale (Mean) |
|---|
| PEGASYS | 1.16 |
| Hydroxyurea | -1.0 |
Number of Participants With Progression of Disease or Death
"Survival and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation after therapy~To estimate survival and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation after therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea) by capturing the rate of progression to a more advanced myeloid malignancy." (NCT01259856)
Timeframe: 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Death | Progression to MF |
|---|
| Hydroxyurea | 1 | 0 |
,| PEGASYS | 0 | 0 |
Number of Participants With Complete Remission (CR)
Number of participants with Complete Remission after 12 months of therapy assessed by hematologic response rates two strata of patients with high risk polycythemia vera (PV) or high risk essential thrombocythemia (ET). Complete remission means no evidence of disease. (NCT01259856)
Timeframe: 12 months
| Intervention | Participants (Count of Participants) |
|---|
| Essential Thrombocythemia | Polycythemia Vera |
|---|
| Hydroxyurea | 19 | 13 |
,| PEGASYS | 17 | 12 |
Number of Participants With Grade 3 and Grade 4 Hematological and Non-hematological Events
Number of Participants with Grade 3 and Grade 4 Hematological and Non-hematological Events using the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 to assess the toxicity, safety and tolerability of therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea). (NCT01259856)
Timeframe: 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3 Hematological event | Grade 4 Hematological event | Grade 3 Non-hematological event | Grade 4 Non-hematological event |
|---|
| Hydroxyurea | 2 | 0 | 14 | 3 |
,| PEGASYS | 3 | 0 | 27 | 2 |
Number of Participants With Partial Remission (PR)
Number of participants with Partial Remission after 12 months of therapy assessed by hematologic response rates two strata of patients with high risk polycythemia vera (PV) or high risk essential thrombocythemia (ET). Partial Remission means decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. (NCT01259856)
Timeframe: 12 months
| Intervention | Participants (Count of Participants) |
|---|
| Essential Thrombocythemia | Polycythemia Vera |
|---|
| Hydroxyurea | 11 | 17 |
,| PEGASYS | 10 | 25 |
Number of Participants With Major Cardiovascular Events After Therapy
(NCT01259856)
Timeframe: 4 years
| Intervention | Participants (Count of Participants) |
|---|
| PEGASYS | 1 |
| Hydroxyurea | 1 |
Change in FACT-G (Functional Assessment of Cancer Therapy - General) Total Score From Baseline to 3 Months
The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life. Change in FACT-G total score from baseline to 3 months was calculated as month 3 score - baseline score. (NCT01274338)
Timeframe: Assessed at baseline and 3 months
| Intervention | score on a scale (Mean) |
|---|
| Arm A (HIP) | -4.9 |
| Arm B (HDI) | -12.9 |
| Arm C (LIP) | -3.4 |
Recurrence-free Survival (RFS; Arm A [HIP] vs. Arm B [HDI])
"Recurrence-free survival is defined as the time from randomization to recurrence or death, whichever occurs first. The following criteria constitute the only acceptable evidence of disease recurrence.~Lung and liver: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease.~Central Nervous System: A positive brain CT or MRI scan or CSF cytology. Cutaneous, Subcutaneous and Lymph Node Recurrence: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease.~Bone and Other Organs: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease identified on two different radiologic studies: i.e., positive nuclear bone scan or PET scan and contrast GI series or ultrasound, X-ray or CT of abdomen for abdominal disease." (NCT01274338)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for years 3-5 and then annually up to 8 years
| Intervention | years (Median) |
|---|
| Arm A (HIP) | 3.9 |
| Arm B (HDI) | 2.4 |
Recurrence-free Survival (RFS; Arm B [HDI] vs. Arm C [LIP])
"Recurrence-free survival is defined as the time from randomization to recurrence or death, whichever occurs first. The following criteria constitute the only acceptable evidence of disease recurrence.~Lung and liver: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease.~Central Nervous System: A positive brain CT or MRI scan or CSF cytology. Cutaneous, Subcutaneous and Lymph Node Recurrence: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease.~Bone and Other Organs: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease identified on two different radiologic studies: i.e., positive nuclear bone scan or PET scan and contrast GI series or ultrasound, X-ray or CT of abdomen for abdominal disease." (NCT01274338)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for years 3-5 and then annually up to 8 years
| Intervention | years (Median) |
|---|
| Arm B (HDI) | 2.5 |
| Arm C (LIP) | 4.5 |
Change in FACT-BRM (Functional Assessment of Cancer Therapy - Biologic Response Modifiers) Total Score From Baseline to 3 Months
The Functional Assessment of Cancer Therapy - Biologic Response Modifiers (FACT-BRM) is a questionnaire including FACT-G (The Functional Assessment of Cancer Therapy - General) and additional sections addressing physical and mental quality of life aspects. It is a 40-item questionnaire with a scale of 0-4. The FACT-BRM total score ranges between 0 and 160. The higher the score, the better the quality of life. Change in FACT-BRM total score from baseline to 3 months is calculated as month 3 score - baseline score. (NCT01274338)
Timeframe: Assessed at baseline and 3 months
| Intervention | score on a scale (Mean) |
|---|
| Arm A (HIP) | -8.3 |
| Arm B (HDI) | -22.7 |
| Arm C (LIP) | -6.2 |
Change in FACIT-D (Functional Assessment of Cancer Therapy - Diarrhea) Diarrhea Subscale Score From Baseline to 3 Months
The diarrhea subscale of The Functional Assessment of Chronic Illness Therapy - Diarrhea (FACIT-D) is an 11-item questionnaire with a scale of 0-4. The FACIT-D diarrhea subscale score ranges between 0 and 44. The higher the score, the better the quality of life. Change in FACIT-D diarrhea subscale score from baseline to 3 months was calculated as month 3 score - baseline score. (NCT01274338)
Timeframe: Assessed at baseline and 3 months
| Intervention | score on a scale (Mean) |
|---|
| Arm A (HIP) | -3.7 |
| Arm B (HDI) | -0.7 |
| Arm C (LIP) | -2.2 |
5-year Overall Survival (OS) Rate (Arm B [HDI] vs. Arm C [LIP])
Overall survival is defined as the time from randomization to death or date last known alive. (NCT01274338)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for years 3-5
| Intervention | proportion of participants (Number) |
|---|
| Arm B (HDI) | 0.67 |
| Arm C (LIP) | 0.72 |
5-year Overall Survival (OS) Rate (Arm A [HIP] vs. Arm B [HDI])
Overall survival is defined as the time from randomization to death or date last known alive. (NCT01274338)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for years 3-5
| Intervention | proportion of participants (Number) |
|---|
| Arm A (HIP) | 0.70 |
| Arm B (HDI) | 0.65 |
End-of-treatment Response
An end-of-treatment response is defined as a negative HCV PCR at 48 weeks after the start of pegylated interferon and ribavirin (NCT01276756)
Timeframe: 48 weeks +- 7 days after starting pegylated interferon and ribavirin
| Intervention | participants (Number) |
|---|
| Standard of Care | 31 |
| Triple Therapy | 29 |
Sustained Virologic Response
sustained virological response is defined as a negative HCV PCR at 180 days after the end of treatment (End of treatment being at 48 weeks for Group A, 52 weeks for Group B). For any patient who stopped treatment prematurely (e.g. due to adverse events) SVR was defined as a negative HCV PCR (polymerase chain reaction) at 180 days after the last dose of all medications (interferon, ribavirin and nitazoxanide) (NCT01276756)
Timeframe: 180 days (+- 7 days) after the end of treatment. (48 weeks for Group A, 52 weeks for Group B, or after the last dose of treatment for patients who stopped prematurely).
| Intervention | participants (Number) |
|---|
| Standard of Care | 24 |
| Triple Therapy | 25 |
Rapid Virological Response
A rapid virologic response is defined as a negative HCV PCR 4 weeks after treatment (NCT01276756)
Timeframe: 28 - 33 days after start of Pegylated interferon and ribavirin
| Intervention | participants (Number) |
|---|
| Standard of Care | 30 |
| Triple Therapy | 25 |
Safety of Nitazoxanide (Number of Participants Experiencing Adverse Events)
The occurence of adverse events that could be linked temporally and reasonably to the administration of the tested drug. (NCT01276756)
Timeframe: throughout the period of treatment and up to 90 days after end of triple therapy
| Intervention | participants (Number) |
|---|
| Standard of Care | 50 |
| Triple Therapy | 47 |
Early Virological Response
"A complete early virologic response is defined as a negative HCV PCR 90 days after the start of pegylated interferon.~A partial early virologic response is defined as a decrease of 2 or more log in HCV PCR at 90 days after the start of pegylated interferon" (NCT01276756)
Timeframe: 90 ± 7 days from the start of pegylated interferon and ribavirin
| Intervention | participants (Number) |
|---|
| Complete early virologic response | Partial early virologic response | No early virologic response response |
|---|
| Standard of Care | 35 | 5 | 10 |
,| Triple Therapy | 36 | 0 | 14 |
Percentage of Participants With Sustained Virologic Response Treated at Interferon Application Centers and Treated at Home
The percentage of participants with SVR-12 and SVR-24 treated at interferon application centers (IAC) and treated at home are presented. (NCT01280656)
Timeframe: At Week 60 (SVR 12) and Week 72 (SVR 24)
| Intervention | percentage of participants (Number) |
|---|
| SVR-12, treated at IAC (n=0, 40, 35) | SVR-12, treated at home (n=14, 81, 57) | SVR-24, treated at IAC (n=0, 40, 35) | SVR-24, treated at home (n=14, 81, 57) |
|---|
| Conventional Interferon Plus Ribavirin | NA | 0 | NA | 64.3 |
,| Peginterferon Alfa-2a Plus Ribavirin | 5.0 | 8.6 | 80.0 | 75.3 |
,| Peginterferon Alfa-2b Plus Ribavirin | 2.9 | 33.3 | 77.1 | 68.4 |
Percentage of Participants With Virologic Response at End of Treatment
Virologic response at EOT was defined as undetectable HCV-RNA at EOT (regardless in which week treatment was concluded). EOT = Week 48. (NCT01280656)
Timeframe: At Week 48
| Intervention | percentage of participants (Number) |
|---|
| Conventional Interferon Plus Ribavirin | 25.8 |
| Peginterferon Alfa-2a Plus Ribavirin | 40.4 |
| Peginterferon Alfa-2b Plus Ribavirin | 35.3 |
Mean Percentage Reduction of Hemoglobin in Treatment Responders and Treatment Non-Responders
The average percentage reduction of hemoglobin (Hb) in treatment responders and treatment non-responders between the conventional group, peginterferon alfa-2a plus and peginterferon alfa-2b is presented. Participants with undetectable HCV RNA at specified time points (Weeks 4/12/18/24/48) were considered as treatment responders. Participants with positive viral load (detectable HCV RNA) at end of treatment regardless of the treatment duration were considered as treatment non-responders. (NCT01280656)
Timeframe: Up to Week 72
| Intervention | mean percentage reduction of hemoglobin (Mean) |
|---|
| Responders (n=0,19,15) | Non-responders (n=10,54,48) |
|---|
| Conventional Interferon Plus Ribavirin | NA | 18.3 |
,| Peginterferon Alfa-2a Plus Ribavirin | 14.4 | 9.8 |
,| Peginterferon Alfa-2b Plus Ribavirin | 15.8 | 12.6 |
Percentage of Participants Who Were Treated at Interferon Application Centers and at Home and Discontinued Treatment
The percentage of participants who were treated at interferon application centers and at home and who discontinued treatment is presented. Participants who did not have viral load assessment at Week 12 were considered treatment failures, except in the specific case where the lack of assessment was not due to treatment shortening in function of response guided therapy. (NCT01280656)
Timeframe: Up to Week 48
| Intervention | percentage of participants (Number) |
|---|
| At the site (n=0,98,126) | At home (n=55,204,137) |
|---|
| Conventional Interferon Plus Ribavirin | NA | 5.5 |
,| Peginterferon Alfa-2a Plus Ribavirin | 17.4 | 11.8 |
,| Peginterferon Alfa-2b Plus Ribavirin | 17.5 | 21.9 |
Percentage of Participants With Early Virologic Response at Week 12
An early virologic response (EVR) was defined as a HCV-RNA decrease of at least two logarithmic scales (2 Log) or 100 times the pretreatment value or non-detection at Week 12 of treatment period. (NCT01280656)
Timeframe: At Week 12
| Intervention | percentage of participants (Number) |
|---|
| Conventional Interferon Plus Ribavirin | 14.5 |
| Peginterferon Alfa-2a Plus Ribavirin | 37.2 |
| Peginterferon Alfa-2b Plus Ribavirin | 35.0 |
Number of Participants With Any Adverse Events and Any Serious Adverse Events
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes. (NCT01280656)
Timeframe: Up to Week 72
| Intervention | participants (Number) |
|---|
| any AE | any SAE |
|---|
| Conventional Interferon Plus Ribavirin | 57 | 2 |
,| Peginterferon Alfa-2a Plus Ribavirin | 285 | 15 |
,| Peginterferon Alfa-2b Plus Ribavirin | 264 | 9 |
Percentage of Participants With Virologic Relapse up to Week 72
Virologic relapse was defined as undetectable HCV-RNA at end of treatment and detectable HCV-RNA at the last follow-up assessment available. If the participant was a responder at end of treatment and was not submitted to any viral load assessment during the follow-up period, he was considered a relapser. (NCT01280656)
Timeframe: Up to Week 72
| Intervention | percentage of participants (Number) |
|---|
| Conventional Interferon Plus Ribavirin | 37.5 |
| Peginterferon Alfa-2a Plus Ribavirin | 22.2 |
| Peginterferon Alfa-2b Plus Ribavirin | 22.8 |
Percentage of Participants With Sustained Virologic Response at 24 Weeks After End of Treatment
SVR was defined as virological response at 24 weeks after EOT, EOT= Week 48. Virologic response was either defined as having undetectable (that is, no hepatitis C virus Ribonucleic acid [HCV RNA] was detected in the participants' plasma samples) or less than 50 IU/mL HCV RNA (that is, the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples). Participants who did not have viral load assessment at Week 12 were considered treatment failures, except in the specific case where the lack of assessment was not due to treatment shortening in function of response guided therapy. (NCT01280656)
Timeframe: At Week 72
| Intervention | percentage of participants (Number) |
|---|
| Conventional Interferon Plus Ribavirin | 62.5 |
| Peginterferon Alfa-2a Plus Ribavirin | 74.6 |
| Peginterferon Alfa-2b Plus Ribavirin | 72.3 |
Percentage of Participants With Sustained Virologic Response at 12 Weeks After End of Treatment
Sustained virological response (SVR) was defined as virological response at 12 weeks after end of treatment (EOT). Virologic response was either defined as having undetectable (that is, no hepatitis C virus Ribonucleic acid [HCV RNA] was detected in the participants' plasma samples) or less than 50 international units/milliliter (IU/mL) HCV RNA (that is, the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples). EOT= Week 48. Participants who did not have viral load assessment at Week 12 were considered treatment failures, except in the specific case where the lack of assessment was not due to treatment shortening in function of response guided therapy. (NCT01280656)
Timeframe: At Week 60
| Intervention | percentage of participants (Number) |
|---|
| Conventional Interferon Plus Ribavirin | 0 |
| Peginterferon Alfa-2a Plus Ribavirin | 7.1 |
| Peginterferon Alfa-2b Plus Ribavirin | 20.8 |
Percentage of Participants With Rapid Virologic Response at Week 4
Rapid virologic response was defined as qualitative or quantitative HCV-RNA (viral load) undetectable (below the lower limit of detection) at Week 4 of treatment period. (NCT01280656)
Timeframe: At Week 4
| Intervention | percentage of participants (Number) |
|---|
| Conventional Interferon Plus Ribavirin | 6.5 |
| Peginterferon Alfa-2a Plus Ribavirin | 21.2 |
| Peginterferon Alfa-2b Plus Ribavirin | 20.3 |
Percentage of Participants With Null Response or No Responder at End of Treatment
Null response or no responders were defined as those participants presenting positive viral load at EOT (regardless of the treatment duration). EOT= Week 48. (NCT01280656)
Timeframe: At Week 48
| Intervention | percentage of participants (Number) |
|---|
| Conventional Interferon Plus Ribavirin | 74.2 |
| Peginterferon Alfa-2a Plus Ribavirin | 59.6 |
| Peginterferon Alfa-2b Plus Ribavirin | 64.7 |
Percentage of Participants Who Discontinued Treatment Due to Adverse Events
The percentage of participants with treatment discontinuation rates due to adverse events (AE) between conventional group, peginterferon alfa-2a and peginterferon alfa-2b is presented. (NCT01280656)
Timeframe: Up to Week 48
| Intervention | percentage of participants (Number) |
|---|
| Conventional Interferon Plus Ribavirin | 1.6 |
| Peginterferon Alfa-2a Plus Ribavirin | 4.5 |
| Peginterferon Alfa-2b Plus Ribavirin | 4.6 |
Number of Participants With Interferon Dose Reduction Rates in Function of the Interferon Type Being Used
The number of participants with Interferon dose reduction rates in function of the interferon type being used are reported (NCT01280656)
Timeframe: At Week 24
| Intervention | participants (Number) |
|---|
| Conventional Interferon Plus Ribavirin | 1 |
| Peginterferon Alfa-2a Plus Ribavirin | 9 |
| Peginterferon Alfa-2b Plus Ribavirin | 29 |
Mean Change From Baseline in the Total Volume of T1 Hypo Intense Lesions at Week 48
(NCT01285401)
Timeframe: Baseline, 48 Weeks
| Intervention | millimeter^3 (mm^3) (Mean) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 20.88 |
| Placebo Interferon Beta-1a (Rebif) | 18.47 |
Mean Change From Baseline in the Total Volume of T2 Lesions at Week 48 (T2 Burden of Disease)
(NCT01285401)
Timeframe: Baseline, 48 Weeks
| Intervention | millimeter^3 (mm^3) (Mean) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 130.38 |
| Placebo Interferon Beta-1a (Rebif) | 95.75 |
Total Number of Reported Relapses at All Time Points up to 48 Weeks
Relapse was defined as neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both as neurological abnormality separated by at least 30 days from onset of a preceding MS attack and Neurological abnormality lasting for at least 24 hours, absence of fever or known infection greater than 37.5 degree centigrade /99.5 degree fahrenheit , objective neurological impairment, correlating with the subject's reported symptoms, defined as either increase in at least one of the functional systems of the EDSS or increase of the total EDSS score and occurrence of paraesthesia, fatigue, mental symptoms, and/or vegetative symptoms without any additional symptom will not be classified as an MS attack. (NCT01285401)
Timeframe: 48 weeks
| Intervention | number of relapse per subject (Mean) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 0.25 |
| Placebo Interferon Beta-1a (Rebif) | 0.34 |
Percentage of Subjects With Disease Activity Free Status (Alternate Definition) at Week 48
Disease activity free (DAF) status was defined as absence of any of the clinical and imaging parameters related to the assessment of disease activity; no relapses, no confirmed expanded disability status scale (EDSS) progression and no new gadolinium (Gd)-enhancing or relaxation time 2 (T2) magnetic resonance imaging (MRI) lesions. Confirmed EDSS progression was defined as an EDSS progression confirmed after 24 weeks. (NCT01285401)
Timeframe: Week 48
| Intervention | percentage of subjects (Number) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 47.8 |
| Placebo Interferon Beta-1a (Rebif) | 37.9 |
Mean Number of Combined Unique Active (CUA) Lesions Per Subject Per Scan at Week 48
CUA lesions was defined as new T1 (Gd enhancing) lesions, new Relaxation time 2 (T2) lesions, or enlarging T2 lesions. (NCT01285401)
Timeframe: 48 Weeks
| Intervention | lesions per subject per scan (Mean) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 1.09 |
| Placebo Interferon Beta-1a (Rebif) | 1.49 |
Number od Subjects With Confirmed EDSS Progression
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. A confirmed EDSS progression was defined EDSS greater than or equal to 1.0 point confirmed during a visit performed 6 months later. An EDSS progression was defined as an increase of the EDSS score of at least 1.0 point compared to baseline (SD1) for subjects with a baseline EDSS ≤ 4.0. For subjects with an EDSS score of 0 at baseline (SD1), EDSS progression was defined as an increase of at least 1.5 points. A confirmed EDSS progression was defined as an EDSS progression confirmed after 24 weeks. (NCT01285401)
Timeframe: Baseline upto 48 Weeks
| Intervention | subjects (Number) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 8 |
| Placebo Interferon Beta-1a (Rebif) | 4 |
Percentage of Subjects With Disease Activity Free Status up to Week 48
Disease activity free status was defined as absence of any of the clinical and imaging parameters related to the assessment of disease activity; no relapses, no expanded disability status scale (EDSS) progression and no new gadolinium (Gd)-enhancing or relaxation time 2 (T2) magnetic resonance imaging (MRI) lesions. (NCT01285401)
Timeframe: Up to Week 48
| Intervention | percentage of subjects (Number) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 37.2 |
| Placebo Interferon Beta-1a (Rebif) | 35.3 |
Number of Subjects With Relapse
Relapse was defined as neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both as neurological abnormality separated by at least 30 days from onset of a preceding MS attack and Neurological abnormality lasting for at least 24 hours, absence of fever or known infection greater than 37.5 degree centigrade /99.5 degree fahrenheit , objective neurological impairment, correlating with the subject's reported symptoms, defined as either increase in at least one of the functional systems of the EDSS or increase of the total EDSS score and occurrence of paraesthesia, fatigue, mental symptoms, and/or vegetative symptoms without any additional symptom will not be classified as an MS attack. (NCT01285401)
Timeframe: Baseline upto 48 weeks
| Intervention | subjects (Number) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 24 |
| Placebo Interferon Beta-1a (Rebif) | 29 |
Annualized Relapse Rate at Week 48
Relapse was defined as neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both as neurological abnormality separated by at least 30 days from onset of a preceding MS attack and Neurological abnormality lasting for at least 24 hours, absence of fever or known infection greater than 37.5 degree centigrade /99.5 degree fahrenheit , objective neurological impairment, correlating with the subject's reported symptoms, defined as either increase in at least one of the functional systems of the EDSS or increase of the total EDSS score and occurrence of paraesthesia, fatigue, mental symptoms, and/or vegetative symptoms without any additional symptom will not be classified as an MS attack. (NCT01285401)
Timeframe: 48 weeks
| Intervention | relapse per year (Mean) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 0.28 |
| Placebo Interferon Beta-1a (Rebif) | 0.41 |
Percentage of Subjects Free From New T1 Hypointense Lesions (Black Holes) at Week 48
(NCT01285401)
Timeframe: 48 Weeks
| Intervention | percentage of subjects (Number) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 78.8 |
| Placebo Interferon Beta-1a (Rebif) | 63.8 |
Percentage of Subjects Free From T1 Gadolinium Enhancing Lesions at Week 48
(NCT01285401)
Timeframe: 48 Weeks
| Intervention | percentage of subjects (Number) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 83.2 |
| Placebo Interferon Beta-1a (Rebif) | 70.7 |
Percentage of Subjects Treated With Glucocorticoids Due to Relapses
Relapse was defined as neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both as neurological abnormality separated by at least 30 days from onset of a preceding MS attack and Neurological abnormality lasting for at least 24 hours, absence of fever or known infection greater than 37.5 degree centigrade /99.5 degree fahrenheit , objective neurological impairment, correlating with the subject's reported symptoms, defined as either increase in at least one of the functional systems of the EDSS or increase of the total EDSS score and occurrence of paraesthesia, fatigue, mental symptoms, and/or vegetative symptoms without any additional symptom will not be classified as an MS attack. (NCT01285401)
Timeframe: Baseline upto 48 weeks
| Intervention | percentage of subjects (Number) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 15.9 |
| Placebo Interferon Beta-1a (Rebif) | 20.7 |
Cumulative Number of New Combined Unique Active (CUA) Lesions at Week 48
CUA lesions was defined as new T1 (Gd enhancing) lesions, new T2 lesions, or enlarging T2 lesions. (NCT01285401)
Timeframe: 48 Weeks
| Intervention | lesions per subject per scan (Mean) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 1.09 |
| Placebo Interferon Beta-1a (Rebif) | 1.49 |
Percentage of Subjects Free From Any Expanded Disability Status Scale (EDSS) Progression at Week 48
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. A confirmed EDSS progression was defined EDSS greater than or equal to 1.0 point confirmed during a visit performed 6 months later. An EDSS progression was defined as an increase of the EDSS score of at least 1.0 point compared to baseline (SD1) for subjects with a baseline EDSS ≤ 4.0. For subjects with an EDSS score of 0 at baseline (SD1), EDSS progression was defined as an increase of at least 1.5 points. A confirmed EDSS progression was defined as an EDSS progression confirmed after 24 weeks. (NCT01285401)
Timeframe: Week 48
| Intervention | percentage of subjects (Number) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 71.7 |
| Placebo Interferon Beta-1a (Rebif) | 75.0 |
Percentage of Relapse-free Subjects at Week 48
A relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. (NCT01285401)
Timeframe: Week 48
| Intervention | percentage of subjects (Number) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 78.8 |
| Placebo Interferon Beta-1a (Rebif) | 75.0 |
Cumulative Number of Relaxation Time 1 (T1) Gadolinium Enhancing Lesions at Week 48
(NCT01285401)
Timeframe: 48 Weeks
| Intervention | lesions per subject per scan (Mean) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 0.36 |
| Placebo Interferon Beta-1a (Rebif) | 0.25 |
Percentage of New T1 Hypointense Lesions (Black Holes) at Week 48 Within the Subgroup of New or Enlarging Non-enhancing T2 Lesions
(NCT01285401)
Timeframe: 48 Weeks
| Intervention | percentage of new T1 hypointense lesions (Mean) |
|---|
| VigantOL Oil Interferon Beta-1a (Rebif) | 20.11 |
| Placebo Interferon Beta-1a (Rebif) | 27.70 |
The Number of Participants Demonstrating Viral Relapse
The table below shows the number of participants who demonstrated viral relapse, defined as undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) at end of treatment (EOT) and detectable HCV RNA during follow-up or detectable HCV RNA at the time points of sustained virologic response (SVR) assessment . The incidence of viral relapse was calculated for participants with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement. (NCT01290731)
Timeframe: Up to 72 weeks
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 4 |
Area Under the Plasma Concentration-time Curve From 0 to 24 Hrs (AUC24h) for TMC435
"The table below shows the median (range) AUC24h values for TMC435 for all participants who received TMC435 for up to 12 weeks. Overall is the median exposure estimate using all available data for each participant in the study. Sparse blood samples were collected during the study (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12)." (NCT01290731)
Timeframe: Overall (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12)
| Intervention | ng.h/mL (Median) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 63261 |
The Number of Participants With Viral Breakthrough
Viral breakthrough was defined as a confirmed increase of greater than 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels from the lowest level reached or a confirmed value of plasma HCV RNA of > 2.0 log10 IU/mL in particpants whose plasma HCV RNA level had previously been below 1.2 log10 IU/mL detectable or undetectable during the treatment period. The table below shows that no viral breakthrough was noted in any participants during the treatment period of the study. (NCT01290731)
Timeframe: Day 1 until end of treatment (EOT [Week 24 or 48])
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 0 |
Plasma Concentrations of TMC435
"The table below shows median (range) TMC435 predose plasma concentration (C0h) values and the TMC435 maximum plasma concentration (Cmax) values for all participants who received TMC435 for up to 12 weeks. Overall is the median exposure estimate using all available data for each participant in the study.Sparse blood samples were collected during the study (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12)." (NCT01290731)
Timeframe: Overall (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12)
| Intervention | ng/mL (Median) |
|---|
| C0h | Cmax |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 1822 | 3440 |
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
The table below shows the percentage of participants with undetectable HCV RNA (defined as less than 1.2 log10 IU/mL during treatment at Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT [Week 24 or 48]). (NCT01290731)
Timeframe: Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT
| Intervention | Percentage of participants (Number) |
|---|
| Week 4 | Week 12 | Week 24 | Week 36 | Week 48 | Week 60 | Week 72 | EOT |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 81.6 | 100.0 | 95.9 | 91.8 | 89.8 | 89.8 | 89.8 | 100.0 |
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
The table below shows the percentage of participants with greater than or equal to 2 log10 IU/mL drop from baseline in plasma HCV RNA at each time point during treatment, at the end of treatment (Week 24 or 48), and post-treatment follow-up. (NCT01290731)
Timeframe: Days 3 and 7, Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT, and follow-up (FU) Weeks 4, 12, and 24
| Intervention | Percentage of participants (Number) |
|---|
| Day 3 | Day 7 | Week 2 | Week 3 | Week 4 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | Week 36 | Week 48 | Week 60 | Week 72 | EOT | FU Week 4 | FU Week 12 | FU Week 24 |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 93.9 | 100.0 | 100.0 | 98.0 | 100.0 | 100.0 | 100.0 | 98.0 | 100.0 | 95.9 | 100.0 | 93.9 | 89.8 | 89.8 | 89.8 | 100 | 100 | 95.9 | 91.8 |
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT)
The table below shows the number of participants with abnormal ALT levels at baseline (Day 1) who achieved normalization of ALT levels (defined as an ALT value less than or equal to the Upper Limit of Normality [ie, 40 IU/mL] at EOT). At baseline, 15/49 participants had abnormal ALT levels. (NCT01290731)
Timeframe: EOT (Week 24 or 48)
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 11 |
The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)
The table below shows the percentage of participants with a SVR24 defined as participants with undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at the end of treatment (Week 24 or 48) and at 24 weeks after the last dose of treatment (Week 48 or 72). (NCT01290731)
Timeframe: Week 48 or 60
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 89.8 |
The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12)
The table below shows the percentage of participants with an SVR12 defined as participants with undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at the end of treatment (Week 24 or 48) who also had undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) 12 weeks after the last dose of treatment (Week 36 or 60). (NCT01290731)
Timeframe: Week 36 or 60
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 95.9 |
Pre- and Post- Interferon Alpha on Human Immunodeficiency Virus Type 1 (HIV-1) Deoxyribonucleic Acid (DNA)
Cell associated HIV nucleic acid levels were measured using a single copy assay, and numbers of cells were quantified using a polymerase chain reaction method that detects C-C chemokine receptor type 5 (CCR5) DNA. (NCT01295515)
Timeframe: week 4 (post) compared to week 0 (pre)
| Intervention | # of copies of DNA/million cells (Number) |
|---|
| Patient #1 HIV DNA Pre | Patient #1 HIV DNA Post | Patient #2 HIV DNA Pre | Patient #2 HIV DNA Post | Patient #3 HIV DNA Pre | Patient #3 HIV DNA Post | Patient #4 HIV DNA Pre | Patient #4 HIV DNA Post | Patient #5 HIV DNA Pre | Patient #5 HIV DNA Post | Patient #6 HIV DNA Pre | Patient #6 HIV DNA Post | Patient #7 HIV DNA Pre | Patient #7 HIV DNA Post |
|---|
| Interferon Treatment | 1200 | 790 | 150 | 150 | 660 | 500 | 400 | 310 | 10 | 19 | 520 | 420 | 390 | 460 |
Fold Change in Ribonucleic Acid (RNA) and Deoxyribonucleic Acid (DNA) in Human Immunodeficiency Virus Type 1 (HIV-1) Genetic Variation in Individuals Undergoing Interferon Therapy
The outcome measure is the fold change in the ratio of HIV RNA to HIV DNA. For the pre and post interferon time point, the level of HIV RNA is divided by the level of HIV DNA and this ratio of the HIV RNA/DNA pre and post interferon is calculated to yield the fold change in HIV RNA/DNA levels. Fold change does not have units. (NCT01295515)
Timeframe: week 4 (post) and week 0 (pre)
| Intervention | fold change (Number) |
|---|
| Patient #1 | Patient #2 | Patient #3 | Patient #4 | Patient #5 | Patient #6 | Patient #7 |
|---|
| Interferon Treatment | 0.408 | 1.44 | 0.684 | 1.12 | 2.24 | 4.37 | 1.05 |
Count of Participants With Serious and Non-serious Adverse Events Assessed by the Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading Adult Adverse Events.
Here is the count of participants with serious and non-serious adverse events assessed by the Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading Adult Adverse Events for severity (mild/moderate/severe), expectedness (expected/unexpected), and relatedness to study drug (definitely, probably, possibly, unlikely, or unrelated). (NCT01295515)
Timeframe: Date consent signed to date off study, approximately 66 months and 2 days.
| Intervention | Participants (Count of Participants) |
|---|
| Interferon Treatment | 7 |
Pre-and Post- Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) in HIV-infected Individuals
The outcome measure is copies of HIV RNA per ml of plasma. HIV RNA levels are measured using a polymerase chain reaction method. (NCT01295515)
Timeframe: week 4 (post) compared to week 0 (pre)
| Intervention | copies/ml (Median) |
|---|
| Patient #1 Pre | Patient #1 Post | Patient #2 Pre | Patient #2 Post | Patient #3 Pre | Patient #3 Post | Patient #4 Pre | Patient #4 Post | Patient #6 Pre | Patient #6 Post | Patient #7 Pre | Patient #7 Post |
|---|
| Interferon Treatment | 0.7 | 3.8 | 0.2 | .02 | 3.8 | 0.8 | .02 | 1.5 | 1.3 | 0.36 | 9.1 | 8.8 |
Pre- and Post- Interferon Alpha on Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA)
Cell associated HIV nucleic acid levels were measured using a single copy assay, and numbers of cells were quantified using a polymerase chain reaction method that detects RNA. (NCT01295515)
Timeframe: week 4 (post) compared to week 0 (pre)
| Intervention | # of copies of HIV RNA/million cells (Number) |
|---|
| Patient #1 HIV RNA Pre | Patient #1 HIV RNA Post | Patient #2 HIV RNA Pre | Patient #2 HIV RNA Post | Patient #3 HIV RNA Pre | Patient #3 HIV RNA Post | Patient #4 HIV RNA Pre | Patient #4 HIV RNA Post | Patient #5 HIV RNA Pre | Patient #5 HIV RNA Post | Patient #6 HIV RNA Pre | Patient #6 HIV RNA Post | Patient #7 HIV RNA Pre | Patient #7 HIV RNA Post |
|---|
| Interferon Treatment | 670 | 180 | 90 | 130 | 810 | 420 | 450 | 390 | 12 | 51 | 850 | 300 | 250 | 310 |
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-267
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; prior to dose on Day 2 (24 hours after Day 1 dose); and at each subsequent study visit. The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The area under the plasma concentration -time curve (AUC; measured in ng*hr/mL) is a method of measurement of the total exposure of a drug in blood plasma. The AUC24 of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. (NCT01314261)
Timeframe: Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; prior to dose on Day 2 (24 hours after Day 1 dose); and at each subsequent study visit up to Week 12
| Intervention | ng*hr/mL (Mean) |
|---|
| ABT-267 (5 mg) Once Daily + pegIFN/RBV | 115 |
| ABT-267 (50 mg) Once Daily + pegIFN/RBV | 2200 |
| ABT-267 (200 mg) Once Daily + pegIFN/RBV | 6130 |
Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing
Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Sustained virologic response was defined as HCV RNA levels < the lower limit of quantification (< 25 IU/mL) 12 weeks after the last dose of pegIFN/RBV. Data are reported as the percentage of participants with SVR12. (NCT01314261)
Timeframe: 12 weeks after the last dose of pegIFN/RBV
| Intervention | percentage of participants (Number) |
|---|
| ABT-267 (5 mg) Once Daily + pegIFN/RBV | 66.7 |
| ABT-267 (50 mg) Once Daily + pegIFN/RBV | 66.7 |
| ABT-267 (200 mg) Once Daily + pegIFN/RBV | 60.0 |
| Placebo + pegIFN/RBV | 33.3 |
Time to Maximum Plasma Concentration (Tmax) of ABT-267
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. (NCT01314261)
Timeframe: Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
| Intervention | Hours (Mean) |
|---|
| ABT-267 (5 mg) Once Daily + pegIFN/RBV | 3.3 |
| ABT-267 (50 mg) Once Daily + pegIFN/RBV | 3.8 |
| ABT-267 (200 mg) Once Daily + pegIFN/RBV | 4.2 |
Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing
Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Sustained virologic response was defined as HCV RNA levels < the lower limit of quantification (< 25 IU/mL) 24 weeks after the last dose of pegIFN/RBV. Data are reported as the percentage of participants with SVR24. (NCT01314261)
Timeframe: 24 weeks after the last dose of pegIFN/RBV
| Intervention | percentage of participants (Number) |
|---|
| ABT-267 (5 mg) Once Daily + pegIFN/RBV | 55.6 |
| ABT-267 (50 mg) Once Daily + pegIFN/RBV | 44.4 |
| ABT-267 (200 mg) Once Daily + pegIFN/RBV | 50.0 |
| Placebo + pegIFN/RBV | 22.2 |
Percentage of Participants With Partial Early Virologic Response (pEVR)
Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Partial EVR was defined as HCV RNA levels that decreased > 2 log10 IU/mL at Week 12 as compared to baseline HCV RNA levels. Data are reported as the percentage of participants with pEVR. (NCT01314261)
Timeframe: Baseline and Week 12
| Intervention | percentage of participants (Number) |
|---|
| ABT-267 (5 mg) Once Daily + pegIFN/RBV | 100.0 |
| ABT-267 (50 mg) Once Daily + pegIFN/RBV | 88.9 |
| ABT-267 (200 mg) Once Daily + pegIFN/RBV | 90.0 |
| Placebo + pegIFN/RBV | 77.8 |
Percentage of Participants With Extended Rapid Virologic Response (eRVR)
Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Extended RVR was defined as HCV RNA levels < the lower level of quantification (< 25 IU/mL) at Weeks 4 through 12. Data are reported as the percentage of participants with eRVR. (NCT01314261)
Timeframe: Week 4 through Week 12
| Intervention | percentage of participants (Number) |
|---|
| ABT-267 (5 mg) Once Daily + pegIFN/RBV | 77.8 |
| ABT-267 (50 mg) Once Daily + pegIFN/RBV | 77.8 |
| ABT-267 (200 mg) Once Daily + pegIFN/RBV | 80.0 |
| Placebo + pegIFN/RBV | 22.2 |
Serum Concentrations of Pegylated Interferon (pegIFN)
Blood samples were collected at each study visit from Week 1 to Week 12. The samples were analyzed for the concentration of pegIFN (measured in ng/mL) using validated analytical methods and pegIFN concentrations in serum were summarized at each visit. Data are reported as the median (range). (NCT01314261)
Timeframe: At each study visit from Week 1 to Week 12
| Intervention | ng/mL (Median) |
|---|
| Week 1 | Week 2 | Week 4 (n=9, 9, 10, 9) | Week 6 (n=8, 9, 9, 9) | Week 8 (n=8, 9, 9, 9) | Week 12 (n=8, 9, 9, 9) |
|---|
| ABT-267 (200 mg) Once Daily + pegIFN/RBV | 4.30 | 7.52 | 8.23 | 14.6 | 12.1 | 15.2 |
,| ABT-267 (5 mg) Once Daily + pegIFN/RBV | 7.50 | 8.75 | 11.8 | 10.9 | 9.91 | 14.4 |
,| ABT-267 (50 mg) Once Daily + pegIFN/RBV | 6.12 | 9.22 | 7.72 | 9.35 | 10.1 | 6.16 |
,| Placebo + pegIFN/RBV | 4.83 | 6.87 | 8.76 | 10.9 | 11.0 | 8.91 |
Percentage of Participants With Complete Early Virologic Response (cEVR)
Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Complete EVR was defined as HCV RNA < the lower limit of quantification (< 25 IU/mL) at Week 12. Data are reported as the percentage of participants with cEVR. (NCT01314261)
Timeframe: Week 12
| Intervention | percentage of participants (Number) |
|---|
| ABT-267 (5 mg) Once Daily + pegIFN/RBV | 100.0 |
| ABT-267 (50 mg) Once Daily + pegIFN/RBV | 88.9 |
| ABT-267 (200 mg) Once Daily + pegIFN/RBV | 80.0 |
| Placebo + pegIFN/RBV | 66.7 |
Plasma Concentrations of Ribavirin (RBV)
Blood samples were collected at each study visit from Week 1 to Week 12. The samples were analyzed for the concentration of RBV (measured in ng/mL) using validated analytical methods and RBV concentrations in plasma were summarized at each visit. Data are reported as the median (range). (NCT01314261)
Timeframe: At each study visit from Week 1 to Week 12
| Intervention | ng/mL (Median) |
|---|
| Week 1 | Week 2 | Week 4 (n=8, 8, 10, 9) | Week 6 (n=8, 9, 9, 9) | Week 8 (n=8, 9, 9, 9) | Week 12 (n=8, 9, 9, 9) |
|---|
| ABT-267 (200 mg) Once Daily + pegIFN/RBV | 1060 | 1420 | 1580 | 1780 | 1650 | 1800 |
,| ABT-267 (5 mg) Once Daily + pegIFN/RBV | 1330 | 1890 | 1900 | 2000 | 2080 | 2510 |
,| ABT-267 (50 mg) Once Daily + pegIFN/RBV | 1470 | 1640 | 1680 | 1510 | 1710 | 1740 |
,| Placebo + pegIFN/RBV | 1190 | 1360 | 1950 | 1900 | 2280 | 1940 |
Percentage of Participants With 4-week Rapid Virologic Response (RVR)
Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Rapid virologic response was defined as HCV RNA levels < the lower limit of detection (< 15 IU/mL) at Week 4. Data are reported as percentage of participants with RVR. (NCT01314261)
Timeframe: Week 4
| Intervention | percentage of participants (Number) |
|---|
| ABT-267 (5 mg) Once Daily + pegIFN/RBV | 33.3 |
| ABT-267 (50 mg) Once Daily + pegIFN/RBV | 55.6 |
| ABT-267 (200 mg) Once Daily + pegIFN/RBV | 70.0 |
| Placebo + pegIFN/RBV | 22.2 |
Maximum Plasma Concentration (Cmax) of ABT-267
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the plasma after administration in a dosing interval. The Cmax of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. (NCT01314261)
Timeframe: Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
| Intervention | ng/mL (Mean) |
|---|
| ABT-267 (5 mg) Once Daily + pegIFN/RBV | 10.7 |
| ABT-267 (50 mg) Once Daily + pegIFN/RBV | 148 |
| ABT-267 (200 mg) Once Daily + pegIFN/RBV | 535 |
Number of New T1 Hypointense Lesions
The total number of new T1 hypointense lesions as assessed by MRI. (NCT01332019)
Timeframe: Week 48, Week 96
| Intervention | lesions (Mean) |
|---|
| Week 49; n=481, 493 | Week 96; n=411, 406 |
|---|
| BIIB017 Q2W | 0.8 | 1.5 |
,| BIIB017 Q4W | 1.4 | 2.8 |
Number of Participants Experiencing Adverse Events (AEs) Serious AEs, and Discontinuations Due to AEs
AE: any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above. Data collected after Amendment 3 took effect were excluded for participants enrolled into study 105MS302 on every 4 week dosing, but not excluded for participants enrolled on every 2 week dosing. (NCT01332019)
Timeframe: up to 4 years
| Intervention | participants (Number) |
|---|
| Any event | Moderate or severe event | Severe event | Event related to study treatment | Serious event | Discontinuing study treatment due to an event | Withdrawing from study due to an event |
|---|
| BIIB017 Q2W | 478 | 348 | 73 | 399 | 90 | 26 | 23 |
,| BIIB017 Q4W | 471 | 343 | 74 | 400 | 113 | 18 | 14 |
Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities
Data collected after Amendment 3 took effect were excluded for participants enrolled into study 105MS302 on every 4 week dosing, but not excluded for participants enrolled on every 2 week dosing. (NCT01332019)
Timeframe: up to 4 years
| Intervention | participants (Number) |
|---|
| White blood cells < 3.0*10^9/L | White blood cells ≥ 16.0*10^9/L | Lymphocytes < 0.8*10^9/L | Lymphocytes < 0.5*10^9/L | Lymphocytes > 12*10^9/L | Segmented neutrophils ≤ 1*10^9/L | Segmented neutrophils < 1.5*10^9/L | Segmented neutrophils ≥ 12*10^9/L | Total absolute neutrophils ≤ 1*10^9/L | Total absolute neutrophils < 1.5*10^9/L | Total absolute neutrophils ≥ 12*10^9/L | Red blood cells ≤ 3.3*10^12/L | Red blood cells ≥ 6.8*10^12/L | Hemoglobin ≤ 100 g/L | Platelet count ≤ 100*10^9/L | Platelet count ≥ 600*10^9/L |
|---|
| BIIB017 Q2W | 86 | 4 | 62 | 7 | 0 | 16 | 84 | 5 | 15 | 83 | 5 | 7 | 0 | 35 | 11 | 2 |
,| BIIB017 Q4W | 28 | 13 | 41 | 2 | 0 | 8 | 31 | 18 | 8 | 31 | 18 | 1 | 0 | 33 | 3 | 2 |
Number of Participants With Shifts From Baseline: Kidney Function and Other Blood Chemistry
Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. For participants who switched to alternative MS medications, data after switch and 14 days after last dose of study treatment are excluded. Data collected after Amendment 3 took effect were excluded for participants enrolled into study 105MS302 on every 4 week dosing, but not excluded for participants enrolled on every 2 week dosing. TSH=thyroid stimulating hormone. (NCT01332019)
Timeframe: Baseline (BIIB017 Treatment Baseline from Study 105MS301) up to 4 years
| Intervention | participants (Number) |
|---|
| Blood urea nitrogen: shift to low; n=529, 546 | Blood urea nitrogen: shift to high; n=527, 543 | Creatinine: shift to low; n=529, 547 | Creatinine: shift to high; n=528, 545 | Bicarbonate: shift to low; n=523, 540 | Bicarbonate: shift to high; n=529, 544 | Sodium: shift to low; n=529, 546 | Sodium: shift to high; n=524, 544 | Potassium: shift to low; n=527, 544 | Potassium: shift to high; n=528, 546 | Chloride: shift to low; n=529, 546 | Chloride: shift to high; n=528, 547 | Glucose: shift to low; n=522, 539 | Glucose: shift to high; n=506, 513 | TSH: shift to low; n=515, 533 | TSH: shift to high; n=518, 539 |
|---|
| BIIB017 Q2W | 1 | 20 | 1 | 8 | 64 | 0 | 3 | 46 | 21 | 20 | 2 | 3 | 51 | 311 | 30 | 55 |
,| BIIB017 Q4W | 0 | 16 | 0 | 15 | 49 | 0 | 0 | 39 | 13 | 17 | 1 | 0 | 54 | 304 | 47 | 37 |
Number of Gd-Enhancing Lesions
The number of Gd-enhancing lesions as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Baseline (start of 105MS302), Week 48, Week 96
| Intervention | lesions (Mean) |
|---|
| Baseline; n=528, 543 | Week 48; n=481, 493 | Week 96; n=411, 407 |
|---|
| BIIB017 Q2W | 0.2 | 0.2 | 0.2 |
,| BIIB017 Q4W | 0.6 | 0.7 | 0.8 |
Number of Participants With Shifts From Baseline: Liver Function Laboratory Values
Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. For participants who switched to alternative MS medications, data after switch and 14 days after last dose of study treatment are excluded. Data collected after Amendment 3 took effect were excluded for participants enrolled into study 105MS302 on every 4 week dosing, but not excluded for participants enrolled on every 2 week dosing. ALT=alanine aminotransferase; AST=aspartate aminotransferase; GGT=gamma-glutamyl transferase. (NCT01332019)
Timeframe: Baseline (BIIB017 Treatment Baseline from Study 105MS301) up to 4 years
| Intervention | participants (Number) |
|---|
| ALT: shift to low; n=528, 546 | ALT: shift to high; n=487, 497 | AST: shift to low; n=528, 546 | AST: shift to high; n=514, 530 | Total bilirubin: shift to low; n=512, 517 | Total bilirubin: shift to high; n=511, 535 | GGT: shift to low; n=529, 545 | GGT: shift to high; n=512, 528 | Alkaline phosphatase: shift to low; n=522, 543 | Alkaline phosphatase: shift to high; n=516, 536 | Lactate dehydrogenase: shift to low; n=529, 547 | Lactate dehydrogenase: shift to high; n=524, 541 |
|---|
| BIIB017 Q2W | 3 | 153 | 8 | 110 | 76 | 16 | 6 | 97 | 5 | 26 | 0 | 30 |
,| BIIB017 Q4W | 3 | 119 | 10 | 75 | 94 | 22 | 16 | 73 | 4 | 28 | 0 | 18 |
Number of Participants With Shifts From Baseline: Urinalysis
Shift to low includes normal to low, high to low, and unknown to low. Shift to high/positive includes normal to high/positive, low to high/positive, negative to high/positive, and unknown to high/positive. For participants who switched to alternative MS medications, data after switch and 14 days after last dose of study treatment are excluded. Data collected after Amendment 3 took effect were excluded for participants enrolled into study 105MS302 on every 4 week dosing, but not excluded for participants enrolled on every 2 week dosing. Pos=positive; RBC=red blood cells; WBC=white blood cells. (NCT01332019)
Timeframe: Baseline (BIIB017 Treatment Baseline from Study 105MS301) up to 4 years
| Intervention | participants (Number) |
|---|
| Specific gravity: shift to low; n=525, 545 | Specific gravity: shift to high/pos; n=528,547 | pH: shift to low; n=529, 547 | pH: shift to high/pos; n=528, 547 | Color: shift to high/pos; n=516, 529 | Blood: shift to high/pos; n=469, 495 | Glucose: shift to high/pos; n=521, 542 | Ketones: shift to high/pos; n=510, 530 | Protein: shift to high/pos; n=380, 391 | RBC: shift to high/pos; n=419, 402 | WBC: shift to high/pos; n=472, 495 | Bilirubin: shift to high/pos; n=529, 547 | Nitrite: shift to high/pos; n=508, 519 | Urobilinogen: shift to high/pos; n=529, 546 |
|---|
| BIIB017 Q2W | 1 | 3 | 0 | 4 | 36 | 167 | 25 | 73 | 277 | 106 | 130 | 1 | 94 | 13 |
,| BIIB017 Q4W | 2 | 13 | 0 | 6 | 33 | 159 | 28 | 64 | 270 | 110 | 116 | 0 | 84 | 7 |
Percentage Change of Whole Brain Volume
Percentage change of whole brain volume as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Baseline (start of 105MS302), Week 48, Week 96
| Intervention | percentage change (Mean) |
|---|
| Change at Week 48; n=402, 418 | Change at Week 96; n=365, 358 |
|---|
| BIIB017 Q2W | -0.453 | -0.788 |
,| BIIB017 Q4W | -0.522 | -0.835 |
Percentage of Participants Who Relapsed
Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. New or recurrent neurologic symptoms that occur less than 30 days following the onset of a relapse were considered part of the same relapse. Participants who did not experience a relapse prior to switching to alternative MS medications, withdrew from study, or Amendment 3 (A3) took effect were censored at the time of switch/withdrawal/A3 effective date. (NCT01332019)
Timeframe: Up to 4 years
| Intervention | percentage of participants (Number) |
|---|
| Did not relapse | Relapsed |
|---|
| BIIB017 Q2W | 77 | 23 |
,| BIIB017 Q4W | 71 | 29 |
Summary of Participant-Reported Treatment Satisfaction: How Convenient or Inconvenient Is It to Take Your Medication as Instructed?
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question How convenient or inconvenient is it to take your medication as instructed? answers were numerically rated from 1 (extremely inconvenient) to 10 (extremely convenient). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=426, 430 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 8.0 | 8.2 | 8.0 |
,| BIIB017 Q4W | 8.2 | 8.3 | 8.3 |
Summary of Participant-Reported Treatment Satisfaction: How Convenient or Inconvenient Is It to Take Your Medication Every 2 Weeks?
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question How convenient or inconvenient is it to take your medication every 2 weeks? answers were numerically rated from 1 (extremely inconvenient) to 10 (extremely convenient). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=426, 430 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 8.4 | 8.4 | 8.5 |
,| BIIB017 Q4W | 8.4 | 8.6 | 8.6 |
Summary of Participant-Reported Treatment Satisfaction: How Likely Would You Be to Continue to Use This Medication?
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question How likely would you be to continue to use this medication? answers were numerically rated from 1 (extremely unlikely) to 10 (extremely likely). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=426, 430 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 8.6 | 8.3 | 8.8 |
,| BIIB017 Q4W | 8.5 | 8.1 | 8.5 |
Summary of Participant-Reported Treatment Satisfaction: How Satisfied or Dissatisfied Are You With the Injection Frequency (Every 2 Weeks)?
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question How satisfied or dissatisfied are you with the injection frequency (every 2 weeks)? answers were numerically rated from 1 (extremely dissatisfied) to 10 (extremely satisfied). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=426, 430 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 8.3 | 8.3 | 8.6 |
,| BIIB017 Q4W | 8.4 | 8.5 | 8.7 |
Summary of Participant-Reported Treatment Satisfaction: How Tolerable or Intolerable Do You Find the Medication?
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question How tolerable or intolerable do you find the medication? answers were numerically rated from 1 (extremely intolerable) to 10 (extremely tolerable). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=425, 430 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 7.0 | 7.1 | 7.3 |
,| BIIB017 Q4W | 6.8 | 7.2 | 7.5 |
Summary of Participant-Reported Treatment Satisfaction: I Am Satisfied With the Dosing Frequency of This Medication.
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement I am satisfied with the dosing frequency (2 times per month) of this medication answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=425, 430 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 8.5 | 8.5 | 8.7 |
,| BIIB017 Q4W | 8.4 | 8.7 | 8.8 |
Summary of Participant-Reported Treatment Satisfaction: Main Reason for Missed Injections
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question Main reason for missed injections? answer choices were given as medication side effects, injection pain, forget to take medication, tired of taking injections, don't think medication is working, or other. Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | participants (Number) |
|---|
| Year 1: medication side effects; n=8, 6 | Year 1: injection pain; n=8, 6 | Year 1: forget to take medication; n=8, 6 | Year 1: tired of taking injections; n=8, 6 | Year 1: don't think medication is working; n=8, 6 | Year 1: other; n=8, 6 | Year 2: medication side effects; n=4, 3 | Year 2: injection pain; n=4, 3 | Year 2: forget to take medication; n=4, 3 | Year 2: tired of taking injections; n=4, 3 | Year 2: don't think medication is working; n=4, 3 | Year 2: other; n=4, 3 | Year 3: medication side effects; n=2, 2 | Year 3: injection pain; n=2, 2 | Year 3: forget to take medication; n=2, 2 | Year 3: tired of taking injections; n=2, 2 | Year 3: don't think medication is working; n=2, 2 | Year 3: other; n=2, 2 |
|---|
| BIIB017 Q2W | 1 | 0 | 1 | 0 | 0 | 4 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 |
,| BIIB017 Q4W | 0 | 0 | 2 | 0 | 0 | 6 | 1 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 1 |
Summary of Participant-Reported Treatment Satisfaction: Over the Past 4 Weeks, Did You Miss Any of Your Injections?
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question Over the past 4 weeks, did you miss any of your injections? answer choices were given as none missed, miss 1 injection, or miss 2 injections. Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | participants (Number) |
|---|
| Year 1: none missed; n=482, 493 | Year 1: 1 missed; n=482, 493 | Year 1: 2 missed; n=482, 493 | Year 2: none missed; n=426, 429 | Year 2: 1 missed; n=426, 429 | Year 2: 2 missed; n=426, 429 | Year 3: none missed; n=81, 88 | Year 3: 1 missed; n=81, 88 | Year 3: 2 missed; n=81, 88 |
|---|
| BIIB017 Q2W | 487 | 4 | 2 | 426 | 2 | 1 | 86 | 1 | 1 |
,| BIIB017 Q4W | 474 | 8 | 0 | 422 | 3 | 1 | 79 | 0 | 2 |
Summary of Participant-Reported Treatment Satisfaction: Overall, How Satisfied or Dissatisfied Are You With This Medication?
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the question Overall, how satisfied or dissatisfied are you with this medication? answers were numerically rated from 1 (extremely dissatisfied) to 10 (extremely satisfied). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=426, 430 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 8.1 | 8.3 | 8.6 |
,| BIIB017 Q4W | 7.9 | 8.2 | 8.2 |
Summary of Participant-Reported Treatment Satisfaction: The Twice a Month Dosing Enables Me to Be More Spontaneous and Flexible.
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement The twice a month dosing enables me to be more spontaneous and flexible, answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=426, 430 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 8.2 | 8.2 | 8.4 |
,| BIIB017 Q4W | 8.1 | 8.3 | 8.5 |
Summary of Participant-Reported Treatment Satisfaction: The Twice a Month Dosing Makes It More Convenient for Me to Travel/Vacation.
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement The twice a month dosing makes it more convenient for me to travel/vacation, answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=426, 430 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 8.2 | 8.2 | 8.5 |
,| BIIB017 Q4W | 8.2 | 8.3 | 8.6 |
Summary of Participant-Reported Treatment Satisfaction: This Medication Enables Me to Focus More on Myself and My Family Rather Than My MS.
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement This Medication Enables Me to Focus More on Myself and My Family Rather Than My MS, answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=426, 430 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 7.8 | 7.8 | 8.3 |
,| BIIB017 Q4W | 7.3 | 7.8 | 8.0 |
Summary of Participant-Reported Treatment Satisfaction: This Medication Improves My Self-Confidence and Self-Reliance.
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement This medication improves my self-confidence and self-reliance, answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=426, 429 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 7.7 | 7.9 | 8.4 |
,| BIIB017 Q4W | 7.5 | 7.9 | 8.1 |
Summary of Participant-Reported Treatment Satisfaction: This Medication Makes It Easy For Me to Carry Out My Daily Responsibilities.
"Participants completed a Treatment Satisfaction Questionnaire composed of a range of 14 questions regarding the participant's perception of treatment satisfaction at the end of each year of treatment. For the statement This medication makes it easy for me to carry out my daily responsibilities (ie, going to work, doing household chores or caring for my family), answers were numerically rated from 1 (strongly disagree) to 10 (strongly agree). Data after Amendment 3 took effect are excluded." (NCT01332019)
Timeframe: Year 1, Year 2, Year 3
| Intervention | units on a scale (Mean) |
|---|
| Year 1; n=482, 496 | Year 2; n=426, 429 | Year 3; n=82, 88 |
|---|
| BIIB017 Q2W | 7.7 | 7.7 | 8.3 |
,| BIIB017 Q4W | 7.4 | 7.8 | 7.9 |
Time to Sustained Disability Progression
Estimated proportion of participants with progression and time to progression based on the Kaplan-Meier product limit method. Sustained disability progression is defined as: at least a 1.0 point increase on the EDSS from 105MS302 baseline EDSS ≥ 1.0 that is sustained for 24 weeks, or at least a 1.5 point increase on the EDSS from 105MS302 baseline EDSS = 0 that is sustained for 24 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Participants were censored at the time of withdrawal/switch/A3 effective date if they withdrew from study, switched to alternative MS medication, or Amendment 3 took effect without a progression. (NCT01332019)
Timeframe: Weeks 12, 24, 28, 72, 96, 120, 144, 168
| Intervention | proportion of participants (Number) |
|---|
| Progressed at 12 weeks | Progressed at 24 weeks | Progressed at 48 weeks | Progressed at 72 weeks | Progressed at 96 weeks | Progressed at 120 weeks | Progressed at 144 weeks | Progressed at 168 weeks |
|---|
| BIIB017 Q2W | 0.007 | 0.023 | 0.045 | 0.057 | 0.069 | 0.085 | 0.096 | NA |
,| BIIB017 Q4W | 0.023 | 0.046 | 0.079 | 0.103 | 0.115 | 0.147 | 0.161 | NA |
Volume of Gd-Enhancing Lesions
The volume of Gd-enhancing lesions as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Baseline (start of 105MS302), Week 48, Week 96
| Intervention | cm^3 (Mean) |
|---|
| Baseline; n=528, 543 | Week 48; n=481, 493 | Week 96; n=411, 407 |
|---|
| BIIB017 Q2W | 0.0348 | 0.0477 | 0.0357 |
,| BIIB017 Q4W | 0.0911 | 0.1172 | 0.1346 |
Volume of T1 Hypointense Lesions
The volume of T1 hypointense lesions as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Baseline (start of 105MS302), Week 48, Week 96
| Intervention | cm^3 (Mean) |
|---|
| Baseline; n=528, 543 | Week 48; n=481, 493 | Week 96; n=411, 407 |
|---|
| BIIB017 Q2W | 3.6320 | 3.6529 | 3.7494 |
,| BIIB017 Q4W | 3.9869 | 4.3062 | 4.3171 |
Volume of T2 Hyperintense Lesions
The volume of T2 hyperintense lesions as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Baseline (start of 105MS302), Week 48, Week 96
| Intervention | cm^3 (Mean) |
|---|
| Baseline; n=528, 543 | Week 48; n=481, 493 | Week 96; n=411, 407 |
|---|
| BIIB017 Q2W | 9.9678 | 9.8335 | 9.9487 |
,| BIIB017 Q4W | 11.4742 | 11.7421 | 12.0257 |
Change From Baseline in Euro Quality of Life (EQ-5D) Index Score
The EQ-5D is a participant-answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Scores of 1, 2, or 3 are possible responses for each of 5 questions (1=no problems, 2=some problems, 3=severe problems). A scoring formula developed by the EuroQol Group is then used to assign utility values for each participant's Health State Profile. A summary index score (EQ-5D index score) is derived from the 5 questions by conversion with this scoring formula and a table of scores. EQ-5D Summary Index values ranged from -0.6 (worst health state) to 1.00 (perfect health state). Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Baseline (start of 105MS302), Weeks 24, 48, 72, 96, 120, 144, 168
| Intervention | units on a scale (Mean) |
|---|
| Baseline; n=527, 544 | Change at Week 24; n=514, 534 | Change at Week 48; n=498, 510 | Change at Week 72; n=472, 491 | Change at Week 96; n=436, 452 | Change at Week 120; n=193, 205 | Change at Week 144; n=88, 98 | Change at Week 168; n=21, 26 |
|---|
| BIIB017 Q2W | 0.76 | 0.00 | 0.00 | 0.00 | -0.01 | 0.00 | 0.01 | 0.02 |
,| BIIB017 Q4W | 0.76 | 0.00 | -0.01 | -0.01 | -0.01 | -0.02 | 0.00 | 0.00 |
Change From Baseline in EQ-5D Visual Analogue Scale (VAS)
The EQ-5D VAS records the participant's self-rated health on a scale from 0-100 where 100 is the 'best imaginable health state' and 0 is the 'worst imaginable health state.' The scale was normalized to a scale of 0 to 1, with higher values indicating a better health state. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Baseline (start of 105MS302), Weeks 24, 48, 72, 96, 120, 144, 168
| Intervention | units on a scale (Mean) |
|---|
| Baseline; n=527, 542 | Change at Week 24; n=511, 532 | Change at Week 48; n=498, 508 | Change at Week 72; n=472, 490 | Change at Week 96; n=436, 450 | Change at Week 120; n=193, 204 | Change at Week 144; n=88, 97 | Change at Week 168; n=21, 26 |
|---|
| BIIB017 Q2W | 77.33 | -0.98 | -0.93 | -1.89 | -2.20 | -0.88 | -0.87 | 0.46 |
,| BIIB017 Q4W | 77.07 | -0.22 | -0.81 | -0.59 | -1.10 | -0.47 | -0.31 | 1.38 |
Number of Relapses Requiring IV Steroid Use
Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: up to 4 years
| Intervention | relapses (Number) |
|---|
| BIIB017 Q4W | 217 |
| BIIB017 Q2W | 181 |
Annualized Relapse Rate (ARR)
Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. The annualized relapse rate is calculated as the total number of relapses occurred during the period for all participants, divided by the total number of person-years followed in the period. (NCT01332019)
Timeframe: up to 4 years
| Intervention | relapses per person-years (Number) |
|---|
| BIIB017 Q4W | 0.189 |
| BIIB017 Q2W | 0.142 |
Change From Baseline in Expanded Disability Status Scale (EDSS)
Change from Baseline in disability as measured by the Expanded Disability Status Scale (EDSS). The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Baseline (start of 105MS302), Weeks 12, 24, 48, 72, 96, 120, 144, 168
| Intervention | units on a scale (Mean) |
|---|
| Baseline; n=516, 535 | Change at Week 12; n=503, 524 | Change at Week 24; n=500, 519 | Change at Week 48; n=488, 497 | Change at Week 72; n=468, 484 | Change at Week 96; n=429, 446 | Change at Week 120; n=187, 205 | Change at Week 144; n=90, 98 | Change at Week 168; n=21, 25 |
|---|
| BIIB017 Q2W | 2.35 | 0.00 | 0.00 | 0.03 | 0.06 | 0.09 | 0.10 | 0.10 | 0.18 |
,| BIIB017 Q4W | 2.43 | 0.02 | 0.02 | 0.08 | 0.13 | 0.15 | 0.19 | 0.23 | 0.24 |
Change From Baseline in Multiple Sclerosis Impact Scale (MSIS)-29 Physical Score
The 29-item MSIS-29 is a disease-specific participant-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Responses use a 5-point Likert scale ranging from 1 to 5. All questions are to be answered. The physical well being assessment portion of the MSIS-29 consists of 20 questions in which participants rate the impact of MS on their day-to-day life during the past two weeks from 1=no impact to 5=extreme impact for a total score of 20-100. A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Baseline (start of 105MS302), Weeks 24, 48, 72, 96, 120, 144, 168
| Intervention | units on a scale (Mean) |
|---|
| Baseline; n=527, 544 | Change at Week 24; n=513, 534 | Change at Week 48; n=498, 510 | Change at Week 72; n=474, 491 | Change at Week 96; n=437, 452 | Change at Week 120; n=193, 205 | Change at Week 144; n=88, 98 | Change at Week 168; n=20, 26 |
|---|
| BIIB017 Q2W | 20.218 | 0.552 | 0.545 | 0.684 | 1.190 | 0.116 | 0.051 | -0.288 |
,| BIIB017 Q4W | 20.494 | -0.152 | 0.462 | 0.937 | 1.471 | 2.654 | 0.327 | 2.250 |
Change From Baseline in SF-12 Physical Component Score (PCS)
The SF-12 is a multipurpose short form survey with 12 questions, all selected from the SF-36 Health Survey. The questions were combined, scored, and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. PCS was computed using the scores of 12 questions and range from 0 to 100, where a 0 score indicates the lowest level of health and 100 indicates the highest level of health. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Baseline (start of 105MS302), Weeks 24, 48, 72, 96, 120, 144, 168
| Intervention | units on a scale (Mean) |
|---|
| Baseline; n=527, 544 | Change at Week 24; n=514, 535 | Change at Week 48; n=498, 510 | Change at Week 72; n=474, 491 | Change at Week 96; n=437, 452 | Change at Week 120; n=193, 205 | Change at Week 144; n=88, 98 | Change at Week 168; n=20, 26 |
|---|
| BIIB017 Q2W | 44.902 | 0.337 | 0.214 | -0.169 | -0.138 | 0.021 | 0.118 | 0.152 |
,| BIIB017 Q4W | 45.154 | 0.138 | -0.351 | -0.270 | -0.150 | -0.118 | -0.256 | -1.558 |
Change From Baseline in Symbol Digit Modalities Test (SDMT)
SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 (worst) to 110 (best). (NCT01332019)
Timeframe: Baseline (start of 105MS302), Weeks 24, 48, 72, 96, 120, 144, 168
| Intervention | units on a scale (Mean) |
|---|
| Baseline; n=523, 543 | Change at Week 24; n=508, 530 | Change at Week 48; n=493, 509 | Change at Week 72; n=472, 489 | Change at Week 96; n=435, 450 | Change at Week 120; n=190, 203 | Change at Week 144; n=88, 96 | Change at Week 168; n=21, 25 |
|---|
| BIIB017 Q2W | 52.744 | -1.106 | -0.864 | -1.012 | -0.231 | -1.099 | -0.906 | -3.840 |
,| BIIB017 Q4W | 52.134 | -0.313 | -0.365 | -0.625 | -0.340 | -1.305 | -1.727 | -4.000 |
Number of New Active Lesions
The number of new active lesions as assessed by MRI. Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Week 48, Week 96
| Intervention | lesions (Mean) |
|---|
| Week 48; n=481, 493 | Week 96; n=411, 406 |
|---|
| BIIB017 Q2W | 2.0 | 3.9 |
,| BIIB017 Q4W | 4.4 | 9.0 |
Number of New or Newly Enlarging T2 Hyperintense Lesions
The total number of new or newly enlarging T2 hyperintense lesions (from Study 105MS302 Baseline) as assessed by magnetic resonance imaging (MRI). Observed data after participants switched to alternative MS medications or after Amendment 3 took effect are excluded. (NCT01332019)
Timeframe: Week 48, Week 96
| Intervention | lesions (Mean) |
|---|
| Week 48; n=481, 493 | Week 96; n=411, 407 |
|---|
| BIIB017 Q2W | 1.9 | 3.9 |
,| BIIB017 Q4W | 4.4 | 8.9 |
Change From Screening in Spatial Recall Test (SPART) Raw Score
Spatial Recall Test (SPART) for visuospatial learning and delayed recall.Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). A checkerboard with ten checkers arranged in a pattern is shown to the subject for ten seconds. The subject is then asked to reproduce the same pattern with ten checkers on an empty checkerboard. The test includes three consecutive trials. The score is the total number of correct responses for the tree trials. The total score ranged from 0 to 30. Higher values represent a better outcome. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | 1.46 |
| Interferon Beta 1b | 3.06 |
Change From Screening in the Volume of Total T1 Hypointense Lesions
Volume of hypointense post-gadolinium T1 lesion component was measured by MRI scan. Means were estimated using a Mixed-effect model with repeated measures (MMRM) by-visit interaction. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | mm^3 (Mean) |
|---|
| Fingolimod | 391.96 |
| Interferon Beta 1b | 213.93 |
Change From Screening in the Percentage of Brain Volume Change
Calculations of brain volume change were performed using the structural image evaluation of normalized atrophy (SIENA), software included in the Functional Magnetic Resonance Imaging of the Brain (FMRIB) software library. SIENA is a fully automated method for estimating temporal brain volume change. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | percentage of brain volume (Mean) |
|---|
| Fingolimod | -0.60 |
| Interferon Beta 1b | -0.96 |
Change From Screening in Word List Generation (WLG)
Word List Generation (COWAT/WLG): The COWAT assesses verbal fluency on semantic stimulus by asking the patient to produce as many words as possible belonging to a semantic category. The test assessed the verbal fluency, recorded all the possible correct word that a patients should give in 90 sec. No maximum range is available. Higher values represent a better outcome. The score was the number of correct words. The more words the patient pronounces, the better it is. We can imagine that the minimum value might be zero words, , but it is not a score scale. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | 0.39 |
| Interferon Beta 1b | 0.24 |
Change From Screening in the Volume of Total T2 Lesions
Change in volume of total T2-weighted lesions by visit were summarized. Negative values indicate improvement (reduction in lesion volume) and positive values worsening (increase in lesion volume (NCT01333501)
Timeframe: Screening (-1 month), 18 months
| Intervention | mm^3 (Mean) |
|---|
| Fingolimod | 176.25 |
| Interferon Beta 1b | 711.81 |
Change From Screening in Selective Reminding Test - Delayed Recall (SRT-D) Raw Score
The tests SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). The Delayed SRT test is the total number of words recalled after a delayed period. The total score ranged from 0 to 12. Higher values represent a better outcome. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | 0.57 |
| Interferon Beta 1b | 0.39 |
Change From Screening in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw Score
Brief Repeatable Battery (BRB)- widely used as a clinical and research tool, with 68% sensitivity and 85% specificity. It consists of the serial administration of 5 tests. One of the tests is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. If a word in LTS is consistently recalled on all subsequent trials, it is then scored as Consistent Long Term Retrieval (CLTR). The total of the words in CLTR of all six trials is summed. The total score ranged from 0 to 72. Higher values represent a better outcome. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | 5.93 |
| Interferon Beta 1b | 3.96 |
Change From Screening in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw Score
Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The patient hears a series of numbers from recordings that are presented at the rate of one every 3 seconds in the first part of the test (PASAT-3). The patient is asked to add each consecutive digit to the one immediately preceding it. Sixty-one digits are presented for each part, and each part has a maximum of 60 correct answers. The total score ranged from 0 to 60. Higher values represent a better outcome. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | 7.14 |
| Interferon Beta 1b | 6.68 |
Change From Screening in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw Score
Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The patient hears a series of numbers from recordings that are presented at the rate of one every 2 seconds in the second part of the test (PASAT-2). The patient was asked to add each consecutive digit to the one immediately preceding it. Sixty-one digits are presented for each part, and each part has a maximum of 60 correct answers. The total score ranged from 0 to 60. Higher values represent a better outcome. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | 4.79 |
| Interferon Beta 1b | 4.42 |
Change From Screening in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score- Card Set 1+2
The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. Free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. The total score ranged from 0 to 64. Higher values represent a better outcome. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | 2.15 |
| Interferon Beta 1b | 7.38 |
Change From Screening in Montgomery-Asberg Depression Rating Scale (MADRS)
MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms). (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | -0.77 |
| Interferon Beta 1b | 0.13 |
Change From Screening in the Number of New T2 Lesions
New T2 lesions at a specific visit were assessed relative to the previous visit scan. The total number of lesions (visit 8 to 18 month) is calculated as the sum of the number of lesions. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Number of new lesions (Mean) |
|---|
| Fingolimod | 1.25 |
| Interferon Beta 1b | 3.33 |
Change From Screening in Symbol Digit Modalities Test (SDMT) Raw Score
Symbol Digit Modality Test (SDMT) for sustained attention and information processing speed. It presents a series of nine symbols, each of which is paired with a single digit labeled 1-9 in a key at the top of the sheet. The reminder of the page has a pseudo-randomized sequence of symbols, and the patient must respond with the digit associated with each of these as quickly as possible. The score is the number of correct answers in 90 seconds. The total score ranged from 0 to 110. Higher values represent a better outcome. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | 2.19 |
| Interferon Beta 1b | 3.93 |
Change From Screening in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2
The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 64. Higher values represent a better outcome (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | 1.52 |
| Interferon Beta 1b | 3.69 |
Change From Screening in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort- Card Set 1+2
The Delis-Kaplan Executive Function System - Sorting Test is one of the nine tests presented in the DKEFS manual and explores the patient's executive abilities. It has a standard form (version A, administered at screening and Month-18 visit) and an alternate form (version B, administered at Month-9 visit). The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. The DKFES test consisted of two testing procedures: free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 16. Higher values represent a better outcome (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | 0.57 |
| Interferon Beta 1b | 0.82 |
Changes in Quality of Life, by Means of the Multiple Sclerosis Quality of Life (MSQoL-54)
A 54 question measure covers 12 domains; assesses mental and physical health. The physical health composite score is a weighted average of the physical health scales, such as physical function, health perceptions, and energy. The mental health composite score is a weighted average of the mental health scales, such as overall quality of life, cognitive function, and health distress. Each domain has a range from 0 to 100 where higher means better. (NCT01333501)
Timeframe: Baseline, 18 months
| Intervention | Score (Least Squares Mean) |
|---|
| Mental health composite score | Physical health composite score |
|---|
| Fingolimod | 4.76 | -1.80 |
,| Interferon Beta 1b | -2.31 | -4.75 |
Change From Screening in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw Score
Brief Repeatable Battery (BRB)- widely used as a clinical and research tool, with 68% sensitivity and 85% specificity. It consists of the serial administration of 5 tests. One of the tests is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. The total score ranged from 0 to 72. Higher values represent a better outcome. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | raw score (Least Squares Mean) |
|---|
| Fingolimod | 6.32 |
| Interferon Beta 1b | 4.46 |
Change From Screening in the Number of T1 Gd+ Enhancing Lesions
Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Number of new lesions (Mean) |
|---|
| Fingolimod | -0.64 |
| Interferon Beta 1b | 0.59 |
Change From Screening in Spatial Recall Test - Delayed Recall (SPART-D)
Spatial Recall Test (SPART) for visuospatial learning and delayed recall.Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). A checkerboard with ten checkers arranged in a pattern was shown to the subject for ten seconds. The subject was then asked to reproduce the same pattern with ten checkers on an empty checkerboard. The test includes three consecutive trials. The score was the total number of correct responses for the tree trials. The total score ranged from 0 to 10. Higher values represent a better outcome. (NCT01333501)
Timeframe: Screening (-1month), 18 month
| Intervention | Raw score (Least Squares Mean) |
|---|
| Fingolimod | 0.41 |
| Interferon Beta 1b | 0.44 |
Changes From Baseline in Fatigue Impact Scale (mFIS, Total Score and Scores of the 3 Individual Domains).
Modified Fatigue Impact Scale (mFIS) questionnaire is described at each time point to evaluate fatigue by means of usual descriptive statistics. Three domains were also defined: Physical Subscale (sum of items 4, 6, 7, 10, 13, 14, 17, 20, 21 and therefore ranging from 0 to 36), Cognitive Subscale (sum of items 1, 2, 3, 5, 11, 12, 15, 16, 18, 19 and therefore ranging from 0 to 40) and Psychosocial Subscale (sum of items 8, 9 and therefore ranging from 0 to 8). Finally, mFIS - overall score ranged from 0 to 80. The mFIS total score was computed as the sum of scores for each item. Lower values represent a better outcome. (NCT01333501)
Timeframe: Baseline, 18 months
| Intervention | Score (Least Squares Mean) |
|---|
| Fingolimod | 2.36 |
| Interferon Beta 1b | 6.67 |
Changes in the Environmental Status Scale Score (ESS)
The Environmental Status Scale (ESS) is used to quickly evaluate a patient for handicap. It was derived from a measure of socio-economic status. It consists of seven parameters: (1) actual work status, (2) financial and economic status, (3) personal residence or home, (4) personal assistance required, (5) transportation, (6) community services, (7) social activity. Each parameter has a single score from minimum 0 to maximum 5. ESS score is the sum of the points for all 7 parameters: minimum score: 0; maximum score: 35. The higher the score the greater the handicap (NCT01333501)
Timeframe: Baseline, 18 month
| Intervention | Score (Mean) |
|---|
| Fingolimod | 1.08 |
| Interferon Beta 1b | 0.91 |
Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE. (NCT01353911)
Timeframe: Treatment period plus the first 14 days of follow-up (up to 50 weeks)
| Intervention | participants (Number) |
|---|
| OL Grazoprevir 100 mg | 34 |
| Grazoprevir 100 mg | 65 |
| Grazoprevir 200 mg | 66 |
| Grazoprevir 400 mg | 23 |
| Grazoprevir 800 mg | 28 |
| Grazoprevir 400 mg/100 mg | 42 |
| Grazoprevir 800 mg/100 mg | 35 |
| Boceprevir 800 mg | 64 |
Percentage of Participants Achieving Complete Early Viral Response (cEVR)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). cEVR was defined as undetectable HCV RNA (target not detected [TND]) at Week 12. 95% confidence intervals provided based on the Clopper-Pearson method. (NCT01353911)
Timeframe: After 12 weeks of treatment with grazoprevir/boceprevir
| Intervention | percentage of participants (Number) |
|---|
| OL Grazoprevir 100 mg | 94.4 |
| Grazoprevir 100 mg | 80.3 |
| Grazoprevir 200 mg | 85.3 |
| Grazoprevir 400 mg | 87.5 |
| Grazoprevir 800 mg | 75.9 |
| Grazoprevir 400 mg/100 mg | 86.0 |
| Grazoprevir 800 mg/100 mg | 86.1 |
| Boceprevir 800 mg | 69.7 |
Percentage of Participants Achieving Rapid Viral Response (RVR)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). RVR was defined as undetectable (TND) HCV RNA at Week 4 of study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. (NCT01353911)
Timeframe: After 4 weeks of treatment with grazoprevir/boceprevir
| Intervention | percentage of participants (Number) |
|---|
| OL Grazoprevir 100 mg | 72.2 |
| Grazoprevir 100 mg | 90.9 |
| Grazoprevir 200 mg | 91.2 |
| Grazoprevir 400 mg | 87.5 |
| Grazoprevir 800 mg | 86.2 |
| Grazoprevir 400 mg/100 mg | 81.4 |
| Grazoprevir 800 mg/100 mg | 83.3 |
| Boceprevir 800 mg | 59.1 |
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). SVR12 was defined as undetectable (TND) HCV RNA at 12 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. (NCT01353911)
Timeframe: 12 weeks after the end of all treatment (up to 60 weeks)
| Intervention | percentage of participants (Number) |
|---|
| OL Grazoprevir 100 mg | 72.2 |
| Grazoprevir 100 mg | 89.4 |
| Grazoprevir 200 mg | 91.2 |
| Grazoprevir 400 mg | 87.5 |
| Grazoprevir 800 mg | 79.3 |
| Grazoprevir 400 mg/100 mg | 93.0 |
| Grazoprevir 800 mg/100 mg | 91.7 |
| Boceprevir 800 mg | 60.6 |
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). SVR24 was defined as undetectable (TND) HCV RNA at 24 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. (NCT01353911)
Timeframe: 24 weeks after the end of all treatment (up to 72 weeks)
| Intervention | percentage of participants (Number) |
|---|
| OL Grazoprevir 100 mg | 72.2 |
| Grazoprevir 100 mg | 86.4 |
| Grazoprevir 200 mg | 92.6 |
| Grazoprevir 400 mg | 87.5 |
| Grazoprevir 800 mg | 79.3 |
| Grazoprevir 400 mg/100 mg | 93.0 |
| Grazoprevir 800 mg/100 mg | 91.7 |
| Boceprevir 800 mg | 57.6 |
Percentage of Participants Achieving Undetectable HCV RNA at Week 72
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. Undetectable HCV RNA (target not detected [TND]) was defined as below the 9.3 IU/ml limit of detection. 95% confidence intervals provided based on the Clopper-Pearson method. (NCT01353911)
Timeframe: Week 72
| Intervention | percentage of participants (Number) |
|---|
| OL Grazoprevir 100 mg | 69.4 |
| Grazoprevir 100 mg | 80.3 |
| Grazoprevir 200 mg | 86.8 |
| Grazoprevir 400 mg | 87.5 |
| Grazoprevir 800 mg | 75.9 |
| Grazoprevir 400 mg/100 mg | 79.1 |
| Grazoprevir 800 mg/100 mg | 83.3 |
| Boceprevir 800 mg | 54.5 |
Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE. (NCT01353911)
Timeframe: Treatment period plus the first 14 days of follow-up (up to 50 weeks)
| Intervention | participants (Number) |
|---|
| OL Grazoprevir 100 mg | 2 |
| Grazoprevir 100 mg | 3 |
| Grazoprevir 200 mg | 4 |
| Grazoprevir 400 mg | 2 |
| Grazoprevir 800 mg | 3 |
| Grazoprevir 400 mg/100 mg | 4 |
| Grazoprevir 800 mg/100 mg | 2 |
| Boceprevir 800 mg | 9 |
Change From Baseline of Local Platelet Count by Visit During Treatment Period A1 of Core Study
Missing platelet counts were imputed using last observation carried forward (LOCF) approach for subjects who achieved platelet response at prior visits. (NCT01355289)
Timeframe: Day 7 and Day 14
| Intervention | cells x 10^9/L (Mean) |
|---|
| Day 7 | Day 14 |
|---|
| Avatrombopag 10 mg (Core Study) | 19.8 | 29.2 |
,| Avatrombopag 20 mg (Core Study) | 26.5 | 57.2 |
,| Avatrombopag 30 mg (Core Study) | 30.9 | 55.4 |
,| Placebo (Core Study) | -0.1 | -0.2 |
Number of Participants Who Initiated Antiviral Treatment by Day 21 of Period A1 of Core Study
Blood draws were taken to monitor platelet counts during the first 21 days of study treatment. When a platelet count of greater than or equal to 100 X 10^9/L was attained, antiviral treatment was initiated. (NCT01355289)
Timeframe: Baseline to Day 21
| Intervention | Participants (Count of Participants) |
|---|
| Yes | No |
|---|
| Avatrombopag 10 mg (Core Study) | 6 | 10 |
,| Avatrombopag 20 mg (Core Study) | 13 | 5 |
,| Avatrombopag 30 mg (Core Study) | 9 | 5 |
,| Placebo (Core Study) | 1 | 16 |
Number of Participants Who Achieved Platelet Response (Greater Than or Equal to 100 x 10^9/L) by Day 21 of Treatment Period A1 of Core Study
A responder was defined as a participant having a platelet count of greater than or equal to 100x10^9/L by Day 21 starting from an average baseline platelet count of greater than 20 x 10^9/L to less than or equal to 70 x 10^9/L. (NCT01355289)
Timeframe: Baseline to Day 21
| Intervention | Participants (Count of Participants) |
|---|
| Yes | No |
|---|
| Avatrombopag 10 mg (Core Study) | 6 | 10 |
,| Avatrombopag 20 mg (Core Study) | 12 | 6 |
,| Avatrombopag 30 mg (Core Study) | 9 | 5 |
,| Placebo (Core Study) | 1 | 16 |
Number of Participants Who Achieved Platelet Count Greater Than 30 X 10^9/L From Baseline to Day 21 During Treatment Period A1 of Core Study
Blood draws were taken to monitor platelet counts. (NCT01355289)
Timeframe: Baseline to Day 21
| Intervention | Participants (Count of Participants) |
|---|
| Yes | No |
|---|
| Avatrombopag 10 mg (Core Study) | 9 | 7 |
,| Avatrombopag 20 mg (Core Study) | 16 | 2 |
,| Avatrombopag 30 mg (Core Study) | 11 | 3 |
,| Placebo (Core Study) | 1 | 16 |
AST Normalisation: AST in Normal Range 12 Weeks Post Treatment, When SVR12=NO
The number of participants with aspartate aminotransferase (AST) in normal range post treatment when patients do not have sustained virological response 12 weeks post treatment. BL=baseline (NCT01358864)
Timeframe: 12 weeks post treatment, up to 60 weeks
| Intervention | participants (Number) |
|---|
| SVR12=NO | BL normal to SVR12 normal | BL elevated to SVR12 normal | No AST data available at SVR12 visit |
|---|
| Null:Faldaprevir 12 Weeks | 96 | 13 | 6 | 27 |
,| Null:Faldaprevir 24 Weeks | 94 | 14 | 3 | 30 |
,| Partial:Faldaprevir 12 Weeks | 24 | 3 | 6 | 6 |
,| Partial:Faldaprevir 24 Weeks | 30 | 3 | 3 | 6 |
,| Partial:Placebo | 28 | 0 | 0 | 23 |
,| Relapser:Faldaprevir 12 Weeks | 30 | 14 | 2 | 7 |
,| Relapser:Faldaprevir 24 Weeks | 31 | 10 | 6 | 3 |
,| Relapser:Placebo | 42 | 0 | 2 | 33 |
ALT Normalisation: ALT in Normal Range 12 Weeks Post Treatment, SVR12=YES
The number of participants with alanine aminotransferase (ALT) in normal range post treatment when patients have sustained virological response 12 weeks post treatment. BL=baseline (NCT01358864)
Timeframe: 12 weeks post treatment, up to 60 weeks
| Intervention | participants (Number) |
|---|
| SVR12=YES | BL normal to SVR12 normal | BL elevated to SVR12 normal | No ALT data available at SVR12 visit |
|---|
| Null:Faldaprevir 12 Weeks | 49 | 13 | 32 | 1 |
,| Null:Faldaprevir 24 Weeks | 46 | 10 | 35 | 0 |
,| Partial:Faldaprevir 12 Weeks | 33 | 13 | 20 | 0 |
,| Partial:Faldaprevir 24 Weeks | 25 | 10 | 11 | 0 |
,| Partial:Placebo | 1 | 0 | 1 | 0 |
,| Relapser:Faldaprevir 12 Weeks | 69 | 31 | 35 | 1 |
,| Relapser:Faldaprevir 24 Weeks | 72 | 31 | 38 | 0 |
,| Relapser:Placebo | 7 | 3 | 3 | 1 |
AST Normalisation: AST in Normal Range at End of Treatment, When SVR12=YES
The number of participants with aspartate aminotransferase (AST) in normal range at the end of treatment (EoT) when patients have sustained virological response 12 weeks post treatment. BL=baseline (NCT01358864)
Timeframe: End of treatment, up to 48 weeks
| Intervention | participants (Number) |
|---|
| SVR12=YES | BL normal to EoT normal | BL elevated to EoT normal | No EoT data available for AST |
|---|
| Null:Faldaprevir 12 Weeks | 49 | 15 | 21 | 1 |
,| Null:Faldaprevir 24 Weeks | 46 | 16 | 20 | 0 |
,| Partial:Faldaprevir 12 Weeks | 33 | 13 | 10 | 0 |
,| Partial:Faldaprevir 24 Weeks | 25 | 10 | 9 | 1 |
,| Partial:Placebo | 1 | 0 | 1 | 0 |
,| Relapser:Faldaprevir 12 Weeks | 69 | 35 | 24 | 0 |
,| Relapser:Faldaprevir 24 Weeks | 72 | 39 | 22 | 0 |
,| Relapser:Placebo | 7 | 2 | 4 | 1 |
Early Treatment Success (ETS)
Percentage of participants with early Treatment Success (ETS) defined as a plasma HCV RNA level <25 IU/mL (undetected or detected) at Week 4 and <25 IU/mL (undetected) at Week 8. (NCT01358864)
Timeframe: Week 4 and Week 8
| Intervention | percentage of participants (Number) |
|---|
| Relapser:Placebo | 4.1 |
| Relapser:Faldaprevir 12 Weeks | 85.9 |
| Relapser:Faldaprevir 24 Weeks | 87.4 |
| Partial:Placebo | 3.4 |
| Partial:Faldaprevir 12 Weeks | 66.7 |
| Partial:Faldaprevir 24 Weeks | 76.4 |
| Null:Faldaprevir 12 Weeks | 58.6 |
| Null:Faldaprevir 24 Weeks | 51.4 |
Virological Response After 24 Weeks of Treatment Discontinuation (SVR24)
Percentage of participants with virological response after 24 weeks of treatment discontinuation (SVR24) defined as plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level <25 IU/mL (undetected) 24 weeks after the originally planned treatment duration. (NCT01358864)
Timeframe: 24 weeks post treatment, up to 72 weeks
| Intervention | percentage of participants (Number) |
|---|
| Relapser & Partial: Placebo | 10.3 |
| Relapser & Partial: Faldaprevir 12 Weeks | 63.5 |
| Relapser & Partial: Faldaprevir 24 Weeks | 59.5 |
| Null:Faldaprevir 12 Weeks | 33.8 |
| Null:Faldaprevir 24 Weeks | 32.9 |
ALT Normalisation: ALT in Normal Range 12 Weeks Post Treatment, When SVR12=NO
The number of participants with alanine aminotransferase (ALT) in normal range post treatment when patients do not have sustained virological response 12 weeks post treatment. BL=baseline (NCT01358864)
Timeframe: 12 weeks post treatment, up to 60 weeks
| Intervention | participants (Number) |
|---|
| SVR12=NO | BL normal to SVR12 normal | BL elevated to SVR12 normal | No ALT data available at SVR12 visit |
|---|
| Null:Faldaprevir 12 Weeks | 96 | 11 | 7 | 27 |
,| Null:Faldaprevir 24 Weeks | 94 | 6 | 9 | 30 |
,| Partial:Faldaprevir 12 Weeks | 24 | 2 | 4 | 6 |
,| Partial:Faldaprevir 24 Weeks | 30 | 4 | 3 | 5 |
,| Partial:Placebo | 28 | 0 | 0 | 23 |
,| Relapser:Faldaprevir 12 Weeks | 30 | 9 | 6 | 7 |
,| Relapser:Faldaprevir 24 Weeks | 31 | 6 | 6 | 3 |
,| Relapser:Placebo | 42 | 0 | 1 | 33 |
ALT Normalisation: ALT in Normal Range at End of Treatment, When SVR12=NO
The number of participants with alanine aminotransferase (ALT) in normal range at the end of treatment (EoT) when patients do not have sustained virological response 12 weeks post treatment. BL=baseline (NCT01358864)
Timeframe: End of treatment, up to 48 weeks
| Intervention | participants (Number) |
|---|
| SVR12=NO | BL normal to EoT normal | BL elevated to EoT normal | No EoT data available for ALT |
|---|
| Null:Faldaprevir 12 Weeks | 96 | 15 | 34 | 1 |
,| Null:Faldaprevir 24 Weeks | 94 | 14 | 38 | 0 |
,| Partial:Faldaprevir 12 Weeks | 24 | 4 | 14 | 0 |
,| Partial:Faldaprevir 24 Weeks | 30 | 4 | 6 | 1 |
,| Partial:Placebo | 28 | 3 | 9 | 0 |
,| Relapser:Faldaprevir 12 Weeks | 30 | 9 | 10 | 0 |
,| Relapser:Faldaprevir 24 Weeks | 31 | 6 | 14 | 0 |
,| Relapser:Placebo | 42 | 9 | 15 | 1 |
ALT Normalisation: ALT in Normal Range at End of Treatment, When SVR12=YES
The number of participants with alanine aminotransferase (ALT) in normal range at the end of treatment when patients have sustained virological response 12 weeks post treatment. BL=baseline (NCT01358864)
Timeframe: End of treatment, up to 48 weeks
| Intervention | participants (Number) |
|---|
| SVR12=YES | BL normal to EoT normal | BL elevated to EoT normal |
|---|
| Null:Faldaprevir 12 Weeks | 49 | 12 | 23 |
,| Null:Faldaprevir 24 Weeks | 46 | 9 | 27 |
,| Partial:Faldaprevir 12 Weeks | 33 | 10 | 14 |
,| Partial:Faldaprevir 24 Weeks | 25 | 8 | 8 |
,| Partial:Placebo | 1 | 0 | 1 |
,| Relapser:Faldaprevir 12 Weeks | 69 | 30 | 29 |
,| Relapser:Faldaprevir 24 Weeks | 72 | 30 | 26 |
,| Relapser:Placebo | 7 | 3 | 4 |
AST Normalisation: AST in Normal Range at End of Treatment, When SVR12=NO
The number of participants with aspartate aminotransferase (AST) in normal range at the end of treatment when patients do not have sustained virological response 12 weeks post treatment. BL=baseline (NCT01358864)
Timeframe: End of treatment, up to 48 weeks
| Intervention | participants (Number) |
|---|
| SVR12=NO | BL normal to EoT normal | BL elevated to EoT normal |
|---|
| Null:Faldaprevir 12 Weeks | 96 | 18 | 24 |
,| Null:Faldaprevir 24 Weeks | 94 | 21 | 28 |
,| Partial:Faldaprevir 12 Weeks | 24 | 3 | 14 |
,| Partial:Faldaprevir 24 Weeks | 30 | 5 | 6 |
,| Partial:Placebo | 28 | 4 | 9 |
,| Relapser:Faldaprevir 12 Weeks | 30 | 16 | 5 |
,| Relapser:Faldaprevir 24 Weeks | 31 | 12 | 9 |
,| Relapser:Placebo | 42 | 19 | 5 |
AST Normalisation: AST in Normal Range 12 Weeks Post Treatment, SVR12=YES
The number of participants with aspartate aminotransferase (AST) in normal range post treatment when patients have sustained virological response 12 weeks post treatment. BL=baseline (NCT01358864)
Timeframe: 12 weeks post treatment, up to 60 weeks
| Intervention | participants (Number) |
|---|
| SVR12=YES | BL normal to SVR12 normal | BL elevated to SVR12 normal | No AST data available at SVR12 visit |
|---|
| Null:Faldaprevir 12 Weeks | 49 | 16 | 28 | 1 |
,| Null:Faldaprevir 24 Weeks | 46 | 17 | 25 | 0 |
,| Partial:Faldaprevir 12 Weeks | 33 | 16 | 16 | 0 |
,| Partial:Faldaprevir 24 Weeks | 25 | 13 | 8 | 0 |
,| Partial:Placebo | 1 | 0 | 1 | 0 |
,| Relapser:Faldaprevir 12 Weeks | 69 | 36 | 29 | 1 |
,| Relapser:Faldaprevir 24 Weeks | 72 | 41 | 28 | 0 |
,| Relapser:Placebo | 7 | 2 | 4 | 1 |
Sustained Virological Response 12 Weeks Post Treatment (SVR12)
Percentage of participants with sustained virological response (SVR12) 12 weeks post treatment defined as plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level <25 IU/mL (undetected) 12 weeks after the originally planned treatment duration. (NCT01358864)
Timeframe: 12 weeks post treatment, up to 60 weeks
| Intervention | percentage of participants (Number) |
|---|
| Relapser & Partial: Placebo | 10.3 |
| Relapser & Partial: Faldaprevir 12 Weeks | 65.4 |
| Relapser & Partial: Faldaprevir 24 Weeks | 61.4 |
| Null:Faldaprevir 12 Weeks | 33.8 |
| Null:Faldaprevir 24 Weeks | 32.9 |
Overall Response Rate (ORR)
"Overall Response Rate (ORR) included Complete Response (CR) and Partial Response (PR).~Complete Response (CR) was defined as disappearance of all symptoms and signs of all measurable disease, lasting for at least four weeks, without appearance of new lesions.~Partial Response (PR) was defined as a > 50% reduction in the sum of the products of the perpendicular diameters of all measurable lesions, lasting for at least four weeks, without appearance of new lesions or enlargement of existing lesions." (NCT01359956)
Timeframe: 18 weeks from start of therapy
| Intervention | participants (Number) |
|---|
| Fotemustine/Dacarbazine/Interferon + Fotemustine/Dacarbazine | 32 |
| Dacarbazine/Interferon + Dacarbazine | 33 |
| Fotemustine/Dacarbazine/Interferon+Dacarbazine/Interferon | 34 |
| Fotemustine/Dacarbazine + Dacarbazine | 31 |
Progression Free Survival (PFS)
"Progression Free Survival (PFS) was defined as the time from the date of randomisation to the date of progression of disease or death from any cause, whichever occurred first, or date of last follow-up for patients without progression and alive at the end of the study.~PFS curves were estimated with the Kaplan - Meier (K-M) method and treatments were compared with a two-sided log-rank test." (NCT01359956)
Timeframe: 12 months
| Intervention | Months (Median) |
|---|
| Fotemustine/Dacarbazine/Interferon + Fotemustine/Dacarbazine | 2.7 |
| Dacarbazine/Interferon + Dacarbazine | 2.5 |
| Fotemustine/Dacarbazine/Interferon+Dacarbazine/Interferon | 2.8 |
| Fotemustine/Dacarbazine + Dacarbazine | 2.5 |
Overall Survival (OS)
"Overall Survival was defined as the time from the date of randomisation to the date of death from any cause or the date of last follow-up for living patients.~OS curves were estimated with the Kaplan - Meier (K-M) method and treatments were compared with a two - sided log - rank test." (NCT01359956)
Timeframe: 24 months
| Intervention | Months (Median) |
|---|
| Fotemustine/Dacarbazine/Interferon + Fotemustine/Dacarbazine | 7.9 |
| Dacarbazine/Interferon + Dacarbazine | 8.6 |
| Fotemustine/Dacarbazine/Interferon+Dacarbazine/Interferon | 9.1 |
| Fotemustine/Dacarbazine + Dacarbazine | 7.7 |
Treatment Efficacy
The primary outcome measure is the number of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following directly observed PEG-IFN alfa-2b in combination with self-administered ribavirin for 12 weeks in participants with non-quantifiable (<15 IU/ml detected and <15 IU/ml undetected) HCV RNA or undetectable HCV RNA on qualitative assay at week 4 of therapy and for 24 weeks in participants with quantifiable (≥15 IU/ml) HCV RNA or detectable HCV RNA on qualitative assay at week 4 of therapy. (NCT01364090)
Timeframe: 36 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Standard Treatment Duration (24 Weeks) | 10 |
| Shortened Treatment Duration (12 Weeks) | 51 |
| Discontinued Prior to RVR | 0 |
Change in Intraocular Pressure (IOP) in the Fellow Eye at Week One Compared to Baseline
Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg. (NCT01376362)
Timeframe: Baseline and 1 Week
| Intervention | mm Hg (Mean) |
|---|
| Interferon Gamma-1b | -1.60 |
Change in Intraocular Pressure (IOP) in the Fellow Eye at Week Two Compared to Baseline
Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg. (NCT01376362)
Timeframe: Baseline and 2 Weeks
| Intervention | mm Hg (Mean) |
|---|
| Interferon Gamma-1b | -2.20 |
Change in Intraocular Pressure (IOP) in the Study Eye at Week One Compared to Baseline
Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg. (NCT01376362)
Timeframe: Baseline and 1 Week
| Intervention | mm Hg (Mean) |
|---|
| Interferon Gamma-1b | 0.40 |
Change in Intraocular Pressure (IOP) in the Study Eye at Week Two Compared to Baseline
Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg. (NCT01376362)
Timeframe: Baseline and 2 Weeks
| Intervention | mm Hg (Mean) |
|---|
| Interferon Gamma-1b | 0.40 |
Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. (NCT01376362)
Timeframe: Baseline and 1 Week
| Intervention | mm^3 (Mean) |
|---|
| Interferon Gamma-1b | 0.14 |
Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. (NCT01376362)
Timeframe: Baseline and 2 Weeks
| Intervention | mm^3 (Mean) |
|---|
| Interferon Gamma-1b | 0.06 |
Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. (NCT01376362)
Timeframe: Baseline and 1 Week
| Intervention | mm^3 (Mean) |
|---|
| Interferon Gamma-1b | -0.02 |
Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. (NCT01376362)
Timeframe: Baseline and 2 Weeks
| Intervention | mm^3 (Mean) |
|---|
| Interferon Gamma-1b | 0.00 |
Proportion of Participants With a Visual Loss of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in the Study Eye
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. (NCT01376362)
Timeframe: Baseline and 2 Weeks
| Intervention | Percentage of Participants (Number) |
|---|
| Interferon Gamma-1b | 0 |
Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week Two Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. (NCT01376362)
Timeframe: Baseline and 2 Weeks
| Intervention | ETDRS Letters (Mean) |
|---|
| Interferon Gamma-1b | 3.20 |
Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week One Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. (NCT01376362)
Timeframe: Baseline and 1 Week
| Intervention | ETDRS Letters (Mean) |
|---|
| Interferon Gamma-1b | 1.60 |
Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week One Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. (NCT01376362)
Timeframe: Baseline and 1 Week
| Intervention | ETDRS Letters (Mean) |
|---|
| Interferon Gamma-1b | 0.20 |
Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. (NCT01376362)
Timeframe: Baseline and 2 Weeks
| Intervention | µm (Mean) |
|---|
| Interferon Gamma-1b | 30.20 |
Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week Two Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. (NCT01376362)
Timeframe: Baseline and 2 Weeks
| Intervention | ETDRS Letters (Mean) |
|---|
| Interferon Gamma-1b | 4.00 |
Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. (NCT01376362)
Timeframe: Baseline and 1 Week
| Intervention | µm (Mean) |
|---|
| Interferon Gamma-1b | 12.00 |
Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. (NCT01376362)
Timeframe: Baseline and 1 Week
| Intervention | µm (Mean) |
|---|
| Interferon Gamma-1b | -38.60 |
Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. (NCT01376362)
Timeframe: Baseline and 2 Weeks
| Intervention | µm (Mean) |
|---|
| Interferon Gamma-1b | -47.40 |
Percentage of Participants Achieving Sustained Virologic Response at Post-treatment Week 12 (SVR12) With rs12979860 Single Nucleotide Polymorphisms at Baseline in the Interleukin-28B Gene
SVR12 was defined as Hepatitis C Virus (HCV) RNA levels NCT01389323)
Timeframe: Post-treatment Week 12
| Intervention | percentage of participants (Number) |
|---|
| Wild Type (CC) (n=20, 24, 10) | Heterozygous (CT) (n=58, 69, 17) | Minor Homozygous (TT) (n=50, 14, 3) |
|---|
| Black/African American Cohort | 80.0 | 53.4 | 36.0 |
,| Latino Cohort | 70.8 | 50.7 | 64.3 |
,| White Non-Latino Cohort | 80.0 | 58.8 | 66.7 |
Percentage of Participants With Hepatitis C Virus (HCV) RNA Levels The limit of detection for HCV RNA levels was 10 IU/mL and the LLOQ was 25 IU/mL. Data for post-treatment Weeks 36 and 48 were based on participants who had achieved virologic response (defined as HCV RNA levels NCT01389323)
Timeframe: Weeks 1, 2, 4, 6, 8, 12; both Weeks 4 and 12; end-of-treatment (up to 48 weeks), or post-treatment Week 24
| Intervention | percentage of participants (Number) |
|---|
| Week 1 | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Both Weeks 4 and 12 | EOT | Post-treatment Week 24 |
|---|
| Black/African American Cohort | 32.8 | 64.1 | 77.3 | 76.6 | 76.6 | 71.1 | 68.0 | 73.4 | 46.9 |
,| Latino Cohort | 44.9 | 72.0 | 85.0 | 81.3 | 81.3 | 80.4 | 77.6 | 79.4 | 57.0 |
,| White Non-Latino Cohort | 33.3 | 60.0 | 66.7 | 80.0 | 76.7 | 76.7 | 56.7 | 93.3 | 63.3 |
Percentage of Participants With Hepatitis C Virus (HCV) RNA Levels The limit of detection for HCV RNA levels was 10 IU/mL and the LLOQ was 25 IU/mL. For analysis purpose, participants were assigned to following 3 race/ethnicity cohorts: Black/African American, Latino, and White non-Latino. Some participants were represented in more than one race/ethnicity cohort. (NCT01389323)
Timeframe: Weeks 1, 2, 4, 6, 8, 12; both Weeks 4 and 12; end-of-treatment (up to 48 weeks), or post-treatment Weeks 12 and 24
| Intervention | percentage of participants (Number) |
|---|
| Week 1 | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Both Weeks 4 and 12 | EOT | Post-treatment Week 12 | Post-treatment Week 24 |
|---|
| Black/African American Cohort | 6.3 | 28.1 | 64.1 | 68.8 | 70.3 | 64.1 | 55.5 | 71.1 | 50.8 | 46.9 |
,| Latino Cohort | 12.1 | 27.1 | 68.2 | 75.7 | 73.8 | 74.8 | 58.9 | 78.5 | 55.1 | 55.1 |
,| White Non-Latino Cohort | 6.7 | 30.0 | 50.0 | 66.7 | 66.7 | 66.7 | 43.3 | 93.3 | 63.3 | 63.3 |
Percentage of Participants Achieving Sustained Virologic Response at Post-treatment Week 12 (SVR12)
SVR12 was defined as Hepatitis C Virus (HCV) RNA levels NCT01389323)
Timeframe: Post-treatment Week 12
| Intervention | percentage of participants (Number) |
|---|
| Black/African American Cohort | 50.8 |
| Latino Cohort | 57.0 |
| White Non-Latino Cohort | 66.7 |
Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination
(NCT01403376)
Timeframe: pre vaccination (baseline) and 28 days post vaccination
| Intervention | ratio post/pre vaccination (Geometric Mean) |
|---|
| H1N1 strain | H3N2 strain | B strain |
|---|
| IFN-β-1 | 3.4 | 4.1 | 4.7 |
,| Teriflunomide 14 mg | 2.3 | 2.6 | 3.0 |
,| Teriflunomide 7 mg | 2.5 | 2.6 | 3.1 |
Percentage of Participants With 2 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination
Percentages of participants with an increase from baseline of 2-fold or more in antibody titers and 90% CIs using normal approximation were calculated for each strain and treatment group. (NCT01403376)
Timeframe: pre vaccination (baseline) and 28 days post vaccination
| Intervention | percentage of participants (Number) |
|---|
| H1N1 strain | H3N2 strain | B strain |
|---|
| IFN-β-1 | 46.5 | 51.2 | 58.1 |
,| Teriflunomide 14 mg | 30.8 | 41.0 | 51.3 |
,| Teriflunomide 7 mg | 35.0 | 35.0 | 47.5 |
Immunoglobulin Levels
(NCT01403376)
Timeframe: pre vaccination (baseline) and 28 days post vaccination
| Intervention | g/L (Mean) |
|---|
| Immunoglobulin M - pre vaccination | Immunoglobulin M - 28-day post vaccination | Immunoglobulin G - pre vaccination | Immunoglobulin G - 28-day post vaccination | Immunoglobulin A - pre vaccination | Immunoglobulin A - 28-day post vaccination |
|---|
| IFN-β-1 | 1.14 | 1.16 | 12.03 | 12.25 | 2.27 | 2.33 |
,| Teriflunomide 14 mg | 1.23 | 1.27 | 9.12 | 9.09 | 1.51 | 1.50 |
,| Teriflunomide 7 mg | 1.28 | 1.30 | 9.35 | 9.57 | 1.65 | 1.63 |
Percentage of Participants With 4 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination
Percentages of participants with an increase from baseline of 4-fold or more in antibody titers and 90% CIs using normal approximation were calculated for each strain and treatment group. (NCT01403376)
Timeframe: pre vaccination (baseline) and 28 days post vaccination
| Intervention | percentage of participants (Number) |
|---|
| H1N1 strain | H3N2 strain | B strain |
|---|
| IFN-β-1 | 39.5 | 41.9 | 51.2 |
,| Teriflunomide 14 mg | 20.5 | 23.1 | 30.8 |
,| Teriflunomide 7 mg | 22.5 | 25.0 | 37.5 |
Percentage of Participants With Antibody Titer ≥40 at 28 Days Post Vaccination
"For each viral strain (H1N1, H3N2, and B), the antibody titer, level of antibodies in blood sample when exposed to antigen, was calculated as the mean of two replicates. If the titer was below or above the limit of detection, the threshold value was used.~The percentage of participants achieving a titer of 40 or more, as well as the 90% confidence interval (CI) using normal approximation were calculated for each strain and treatment group." (NCT01403376)
Timeframe: 28 days post vaccination
| Intervention | percentage of participants (Number) |
|---|
| H1N1 strain | H3N2 strain | B strain |
|---|
| IFN-β-1 | 97.7 | 90.7 | 93.0 |
,| Teriflunomide 14 mg | 97.4 | 76.9 | 97.4 |
,| Teriflunomide 7 mg | 97.5 | 90.0 | 97.5 |
Participants' Response
Complete Response (CR): Disappearance of all clinical evidence of active tumors for a minimum of 8 weeks. Partial Response (PR): 50% or greater decrease in sum of products all measured lesions persisting for at least 4 weeks. No Change: Steady state or change of +/- 25% of tumor size and no progression for minimum of 8 weeks with no appearance of new lesions. Progressive Disease: > 25 % increase in size of any measurable lesion or appearance of significant new lesions. (NCT01404936)
Timeframe: After 6 courses (3 months)
| Intervention | participants (Number) |
|---|
| Complete Response | Uncomfirmed Complete Response | Partial Response | Progressive Disease |
|---|
| Interferon-2A + Chemotherapy | 23 | 2 | 3 | 1 |
Drug Exposure
Total number of patients receiving treatment over specified time intervals. (NCT01405027)
Timeframe: End of treatment up to treatment week 48
| Intervention | participants (Number) |
|---|
| Days 1-7 | Days 8-14 | Days 15-28 | Days 29-56 | Days 57-84 | Days 85-168 | Days 169-252 | Days >252 |
|---|
| Group A - HCEE | 84 | 84 | 83 | 81 | 78 | 73 | 49 | 26 |
,| Group B - Community Sites | 113 | 112 | 110 | 108 | 100 | 91 | 75 | 30 |
Determination of the Rate of Sustained Viral Response (SVR) for HCV Patients Treated With Boceprevir, Peginterferon and Ribavirin at Community Sites and at HCEEs.
Rate of SVR was defined as the percentage of participants with HCV-RNA undetectable at follow-up Week 24. All percentages were based on the total number of participants originally randomized/enrolled to that particular arm. (NCT01405027)
Timeframe: Follow-up week 24
| Intervention | percentage of participants (Number) |
|---|
| Negative (percent) | Positive (percent) | Missing (percent) |
|---|
| Group A - HCEE | 48.8 | 23.8 | 27.4 |
,| Group B - Community Sites | 46.0 | 26.5 | 27.4 |
Treatment Duration Compliance Rate
The primary objective will be to define treatment duration compliance rate (calculated as the actual treatment duration in weeks divided by the expected duration in weeks) based on individual patient treatment goals as defined in the OPTIMAL protocol for HCV patients treated with boceprevir, peginterferon and ribavirin for up to 48 weeks. Rates will be reported for HCEEs (Group A) and community sites enrolled in the Program (Group B). (NCT01405027)
Timeframe: End of treatment up to treatment week 48
| Intervention | Percentage of compliance (Mean) |
|---|
| Group A - HCEE | 85.4 |
| Group B - Community Sites | 83.8 |
Number of Participants With Adverse Events
Description of the adverse events and rate of events of boceprevir, peginterferon and ribavirin in HCV patients treated at community sites and at HCEEs (NCT01405027)
Timeframe: Throughout entire study, at end of treatment and follow up week 24
| Intervention | participants (Number) |
|---|
| Group A - HCEE | 77 |
| Group B - Community Sites | 95 |
Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab
Number of participants positive for anti-drug antibodies (ADAs) to ocrelizumab is the number of post- baseline evaluable participants determined to have treatment-induced ADA or treatment-enhanced ADA during the study period. (NCT01412333)
Timeframe: Baseline up to Week 96
| Intervention | participants (Number) |
|---|
| Positive sample at baseline (n= 407, 402) | Positive for ADA post-baseline (n= 403, 405) |
|---|
| Interferon Beta-1a 44 mcg SC | 2 | 5 |
,| Ocrelizumab | 4 | 2 |
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score to Week 96
MSFC score consists of: A) Timed 25-Foot walk; B) 9-Hole Peg Test (9-HPT); and C) Paced Auditory Serial Addition Test (PASAT-3 version). The MSFCS is based on the concept that scores for these three dimensions (arm, leg, and cognitive function) are combined to create a single score (the MSFC) that can be used to detect change over time in a group of participants with MS. Since the three primary measures differ in what they actually measure, a common composite score for the three different measures i.e., Z- score was selected for the purpose. MSFC Score = {Z arm, average + Z leg, average + Z cognitive} / 3.0. The results from each of these three tests are transformed into Z-scores and averaged to yield a composite score for each participant at each time point. A score of +1 indicates that, on average, an individual scored 1 standard deviation (SD) better than the reference population and a score of -1 indicates that an individual scored 1 SD worse than the reference population. (NCT01412333)
Timeframe: Baseline, Week 96
| Intervention | Z-score (Mean) |
|---|
| Unadjusted Baseline mean (n= 342, 358) | Adjusted Week 96 mean (n= 269, 308) |
|---|
| Interferon Beta-1a 44 mcg SC | -0.001 | 0.169 |
,| Ocrelizumab | 0.026 | 0.276 |
Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks During the Double-Blind Treatment Period
Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) >=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (<=) 5.5 B) >=0.5 point from the baseline EDSS score when the baseline score was >5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 24 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment. (NCT01412333)
Timeframe: Week 104
| Intervention | weeks (Median) |
|---|
| Interferon Beta-1a 44 mcg SC | NA |
| Ocrelizumab | NA |
Percentage of Participants Who Have No Evidence of Disease Activity (NEDA) up to Week 96
NEDA was defined only for participants with a baseline EDSS score >=2.0. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). Participants who completed the 96- week treatment period were considered as having evidence of disease activity if at least one protocol- defined relapse (PDR), a confirmed disability progression (CDP) event or at least one MRI scan showing MRI activity (defined as Gd-enhancing T1 lesions, or new or enlarging T2 lesions) was reported during the 96-week treatment period, otherwise the participant was considered as having NEDA. (NCT01412333)
Timeframe: Week 96
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 24.1 |
| Ocrelizumab | 43.9 |
Exposure to Ocrelizumab (Area Under the Concentration - Time Curve, AUC)
AUC represents total drug exposure for one dosing interval after the 4th dose. (NCT01412333)
Timeframe: Pre-infusion at Weeks 1, 24, 48, 72; and 30 minutes post-infusion at Week 72; at any time during Weeks 84 and 96
| Intervention | micrograms per milliter*day (Mean) |
|---|
| Ocrelizumab | 3513 |
Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double Blind Treatment
The total number of new and/or enlarging T2 lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96. (NCT01412333)
Timeframe: Baseline up to week 96
| Intervention | lesions (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 2103 |
| Ocrelizumab | 380 |
Number of Participants With Adverse Events (AEs)
AEs included infusion related reactions (IRRs) and serious MS relapses, but excluded non-serious MS relapses. Serious Adverse Events (SAEs) included serious MS relapses and serious IRRs. (NCT01412333)
Timeframe: Baseline up to Week 96
| Intervention | participants (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 357 |
| Ocrelizumab | 360 |
Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks
ARR was protocol-defined and calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of exposure to that treatment. (NCT01412333)
Timeframe: Week 96
| Intervention | relapses/participant year of treatment (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 0.290 |
| Ocrelizumab | 0.155 |
Number of T1 Gadolinium (Gd)-Enhancing Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double-Blind Treatment
The total number of T1 gadolinium-enhancing lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96. (NCT01412333)
Timeframe: Baseline up to week 96
| Intervention | lesions (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 465 |
| Ocrelizumab | 21 |
Number of T1 Hypointense Lesions During the Double-Blind Treatment
The total number of new T1-Hypo-Intense Lesions (Chronic Black Holes) for all participants in the treatment group was calculated as the sum of the individual number of new lesions at Weeks 24, 48, and 96. (NCT01412333)
Timeframe: Baseline up to week 96
| Intervention | lesions (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 1484 |
| Ocrelizumab | 567 |
Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96
"Brain volume was recorded as an absolute normalized value at the baseline visit then recorded at subsequent visits as a percentage change relative to the absolute value at the baseline visit. Therefore, brain volume at Week 24 was calculated as the brain volume at the baseline visit multiplied by 1 + ([percentage change in brain volume from baseline visit to Week 24]/100). Estimates are from analysis based on mixed-effect model of repeated measures (MMRM) using unstructured covariance matrix: Percentage Change = Brain Volume at Week 24 + Geographical Region (US vs. ROW) + Baseline EDSS (< 4.0 vs. >= 4.0) + Week + Treatment + Treatment*Week (repeated values over Week) + Brain Volume at Week 24*Week. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis)." (NCT01412333)
Timeframe: From week 24 up to week 96
| Intervention | percent change (Mean) |
|---|
| Interferon Beta-1a 44 mcg SC | -0.75 |
| Ocrelizumab | -0.638 |
Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks
Disability improvement was assessed only for the subgroup of participants with a baseline EDSS score of >= 2.0. It was defined as a reduction in EDSS score of: A) >=1.0 from the baseline EDSS score when the baseline score was >=2 and <=5.5 B) >= 0.5 when the baseline EDSS score > 5.5. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. (NCT01412333)
Timeframe: Week 96
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a 44 mcg SC | 18.83 |
| Ocrelizumab | 21.38 |
Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks During the Double-Blind Treatment Period
Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) >=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (<=) 5.5 B) >=0.5 point from the baseline EDSS score when the baseline score was >5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment. (NCT01412333)
Timeframe: Week 104
| Intervention | weeks (Median) |
|---|
| Interferon Beta-1a 44 mcg SC | NA |
| Ocrelizumab | NA |
Percentage of Participants Other Than Genotype 1 With Sustained Virologic Response at Post Treatment Week 12 (SVR12)
SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. (NCT01428063)
Timeframe: Week 12 (Follow-up period)
| Intervention | Percentage of participants (Number) |
|---|
| Daclatasvir + Asunaprevir | 85.9 |
| DCV + ASV + pegIFN-2a+ Ribavirin (Genotype 4) | 90.0 |
| DCV + ASV + pegIFN-2a+ RBV (Prior DCV Failures) | 40.0 |
| DCV + ASV + pegIFN-2a+ RBV (Prior ASV Failures) | 100.0 |
| DCV + ASV + pegIFN-2a+ RBV (Prior BOC Failures) | 90.9 |
| DCV + ASV + pegIFN-2a+ RBV (Prior TVR Failures) | 76.9 |
| DCV + ASV + pegIFN-2a+ RBV (Treatment Naive) | 84.0 |
| DCV + ASV + pegIFN-2a+ RBV (pegIFNα /RBV Relapsers) | 88.9 |
| DCV + pegIFN-2a+ RBV | 50.0 |
Percentage of Participants With Complete Early Virologic Response (cEVR)
cEVR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at week 12. (NCT01428063)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| Daclatasvir + Asunaprevir | 87.9 |
| DCV + ASV + pegIFN-2a+ Ribavirin | 95.8 |
| DCV + ASV + pegIFN-2a+ RBV (Prior DCV Failures) | 90.0 |
| DCV + ASV + pegIFN-2a+ RBV (Prior ASV Failures) | 100.0 |
| DCV + ASV + pegIFN-2a+ RBV (Prior BOC Failures) | 90.9 |
| DCV + ASV + pegIFN-2a+ RBV (Prior TVR Failures) | 92.3 |
| DCV + ASV + pegIFN-2a+ RBV (Treatment Naive) | 76.0 |
| DCV + ASV + pegIFN-2a+ RBV (pegIFNα /RBV Relapsers) | 88.9 |
| DCV + pegIFN-2a+ RBV | 83.3 |
Percentage of Participants With End of the Treatment Response (EOTR)
EOTR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at end of treatment. (NCT01428063)
Timeframe: End of the study (Week 24)
| Intervention | Percentage of participants (Number) |
|---|
| Daclatasvir + Asunaprevir | 85.9 |
| DCV + ASV + pegIFN-2a+ Ribavirin | 97.9 |
| DCV + ASV + pegIFN-2a+ RBV (Prior DCV Failures) | 90.0 |
| DCV + ASV + pegIFN-2a+ RBV (Prior ASV Failures) | 100.0 |
| DCV + ASV + pegIFN-2a+ RBV (Prior BOC Failures) | 90.9 |
| DCV + ASV + pegIFN-2a+ RBV (Prior TVR Failures) | 92.3 |
| DCV + ASV + pegIFN-2a+ RBV (Treatment Naive) | 84.0 |
| DCV + ASV + pegIFN-2a+ RBV (pegIFNα /RBV Relapsers) | 88.9 |
| DCV + pegIFN-2a+ RBV | 83.3 |
Percentage of Participants With Extended Rapid Virologic Response (eRVR)
eRVR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at both weeks 4 and 12. (NCT01428063)
Timeframe: Week 4 and 12
| Intervention | Percentage of participants (Number) |
|---|
| Daclatasvir + Asunaprevir | 67.7 |
| DCV + ASV + pegIFN-2a+ Ribavirin | 87.5 |
| DCV + ASV + pegIFN-2a+ RBV (Prior DCV Failures) | 70.0 |
| DCV + ASV + pegIFN-2a+ RBV (Prior ASV Failures) | 83.3 |
| DCV + ASV + pegIFN-2a+ RBV (Prior BOC Failures) | 81.8 |
| DCV + ASV + pegIFN-2a+ RBV (Prior TVR Failures) | 76.9 |
| DCV + ASV + pegIFN-2a+ RBV (Treatment Naive) | 64.0 |
| DCV + ASV + pegIFN-2a+ RBV (pegIFNα /RBV Relapsers) | 88.9 |
| DCV + pegIFN-2a+ RBV | 83.3 |
Percentage of Participants With Rapid Virologic Response (RVR) at Post Treatment Week 4
RVR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at Week 4. (NCT01428063)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| Daclatasvir + Asunaprevir | 72.7 |
| DCV + ASV + pegIFN-2a+ Ribavirin | 91.7 |
| DCV + ASV + pegIFN-2a+ RBV (Prior DCV Failures) | 70.0 |
| DCV + ASV + pegIFN-2a+ RBV (Prior ASV Failures) | 83.3 |
| DCV + ASV + pegIFN-2a+ RBV (Prior BOC Failures) | 90.9 |
| DCV + ASV + pegIFN-2a+ RBV (Prior TVR Failures) | 76.9 |
| DCV + ASV + pegIFN-2a+ RBV (Treatment Naive) | 76.0 |
| DCV + ASV + pegIFN-2a+ RBV (pegIFNα /RBV Relapsers) | 88.9 |
| DCV + pegIFN-2a+ RBV | 83.3 |
Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24)
SVR24 was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected at follow-up week 24. (NCT01428063)
Timeframe: Week 24 (Follow-up)
| Intervention | Percentage of participants (Number) |
|---|
| Daclatasvir + Asunaprevir | 84.8 |
| DCV + ASV + pegIFN-2a+ Ribavirin | 95.8 |
| DCV + ASV + pegIFN-2a+ RBV (Prior DCV Failures) | 40.0 |
| DCV + ASV + pegIFN-2a+ RBV (Prior ASV Failures) | 100.0 |
| DCV + ASV + pegIFN-2a+ RBV (Prior BOC Failures) | 90.9 |
| DCV + ASV + pegIFN-2a+ RBV (Prior TVR Failures) | 76.9 |
| DCV + ASV + pegIFN-2a+ RBV (Treatment Naive) | 84.0 |
| DCV + ASV + pegIFN-2a+ RBV (pegIFNα /RBV Relapsers) | 88.9 |
| DCV + pegIFN-2a+ RBV | 50.0 |
Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) for All Nonresponders With Genotype 1 Hepatitis C Virus (HCV)
SVR12 defined as HCV RNANCT01428063)
Timeframe: Week 12 (Follow-up period)
| Intervention | Percentage of participants (Number) |
|---|
| Daclatasvir + Asunaprevir + PegIFNα-2a + Ribavirin (NR) | 94.6 |
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Who Died During the Study
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. (NCT01428063)
Timeframe: For AEs: Day 1 until last visit. For SAEs: Day 1 until 30 days post discontinuation of dosing or participation
| Intervention | Participants (Number) |
|---|
| SAEs | AEs leading to discontinuation of therapy | Death |
|---|
| Daclatasvir + Asunaprevir | 4 | 2 | 0 |
,| DCV + ASV + pegIFN-2a+ RBV (pegIFNα /RBV Relapsers) | 0 | 0 | 0 |
,| DCV + ASV + pegIFN-2a+ RBV (Prior ASV Failures) | 0 | 1 | 0 |
,| DCV + ASV + pegIFN-2a+ RBV (Prior BOC Failures) | 2 | 0 | 0 |
,| DCV + ASV + pegIFN-2a+ RBV (Prior DCV Failures) | 0 | 0 | 0 |
,| DCV + ASV + pegIFN-2a+ RBV (Prior TVR Failures) | 0 | 0 | 0 |
,| DCV + ASV + pegIFN-2a+ RBV (Treatment Naive) | 1 | 2 | 0 |
,| DCV + ASV + pegIFN-2a+ Ribavirin | 0 | 2 | 0 |
,| DCV + pegIFN-2a+ RBV | 0 | 0 | 0 |
Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis
RVR was defined as the proportion of participants below the assay lower limit of detection (LOD) <18 International units per milliliter (IU/mL) for Hepatitis C virus (HCV) ribonucleic acid (RNA) after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure . Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants. (NCT01439373)
Timeframe: Day 28
| Intervention | Participants (Count of Participants) |
|---|
| HCV RNA >= Low Limit of Quantification (LLOQ) | Undetectable HCV RNA |
|---|
| GSK2336805 60 mg + PEG + RIBA | 3 | 8 |
,| Placebo + PEG + RIBA | 3 | 1 |
Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses)
RVR was defined as the proportion of participants LOD <18 IU/mL for HCV RNA after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure. Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants. The primary and supportive analysis differs from the nominal analysis as supportive analysis is assessed at Day 28 ± 2 (2 days visit window) whereas, the nominal analysis was assessed at Day 28. (NCT01439373)
Timeframe: Day 28
| Intervention | Participants (Count of Participants) |
|---|
| Undetectable HCV RNA | HCV RNA >= LLOQ |
|---|
| GSK2336805 60 mg + PEG + RIBA | 7 | 4 |
,| Placebo + PEG + RIBA | 1 | 3 |
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period
AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. (NCT01439373)
Timeframe: Up to Day 28
| Intervention | Participants (Count of Participants) |
|---|
| Any AE | Any SAE |
|---|
| GSK2336805 60 mg + PEG + RIBA | 11 | 0 |
,| Placebo + PEG + RIBA | 4 | 0 |
Number of Participants With HCV Genotype 1 With Virologic Response
Serum for determination of HCV genotype was collected at the screening visit. Genotype was determined by the VERSANT HCV genotype 2.0 Assay (LiPA). Number of participants with HCV genotype 1 were reported. (NCT01439373)
Timeframe: Day 7, 14 and 21
| Intervention | Participants (Count of Participants) |
|---|
| Day 7, Undetectable HCV RNA | Day 7, Detectable HCV RNA but < LLOQ | Day 7, HCV RNA >= LLOQ | Day 14, Undetectable HCV RNA | Day 14, Detectable HCV RNA but < LLOQ | Day 14, HCV RNA >= LLOQ | Day 21, Undetectable HCV RNA | Day 21, Detectable HCV RNA but < LLOQ | Day 21, HCV RNA >= LLOQ |
|---|
| GSK2336805 60 mg + PEG + RIBA | 1 | 1 | 9 | 4 | 2 | 5 | 7 | 1 | 3 |
,| Placebo + PEG + RIBA | 0 | 0 | 4 | 0 | 0 | 4 | 0 | 0 | 4 |
Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28
Abnormalities were graded according to the modified DAIDS version 1.0. Shift from Baseline to worst post Baseline toxicity grade were presented for Day 1 to Day 28. The toxicity Grades were, Grade 1: mild (no or minimal interference with usual social & functional activities); Grade 2: moderate (greater than minimal interference with usual social and functional activities); Grade 3: severe (inability to perform usual social and functional activities); Grade 4: potentially life threatening (inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death). Clinical chemistry parameters were alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatine phosphokinase, total CO2, chloride, creatinine, glucose, sodium, phosphate, potassium, total albumin, total bilirubin, and direct bilirubin. Only participants with change in toxicity grades are reported. (NCT01439373)
Timeframe: Baseline (Day 1) and 28
| Intervention | Participants (Count of Participants) |
|---|
| Alanine aminotransferase, No toxicity | Alanine aminotransferase, Grade 1 | Albumin, No toxicity | Albumin, Grade 1 | Aspartate aminotransferase, No toxicity | Aspartate aminotransferase, Grade 1 | Aspartate aminotransferase, Grade 2 | Total Bilirubin, No toxicity | Total Bilirubin, Grade 1 | Total Bilirubin, Grade 2 | Carbon dioxide, No toxicity | Carbon dioxide, Grade 1 | Creatine phosphokinase, No toxicity | Creatine phosphokinase, Grade 1 | Glucose, No toxicity | Glucose, Grade 1 | Glucose, Grade 2 | Phosphorus, inorganic, No toxicity | Phosphorus, inorganic, Grade 1 | Phosphorus, inorganic, Grade 2 | Potassium, No toxicity | Potassium, Grade 1 | Sodium, No toxicity | Sodium, Grade 2 |
|---|
| GSK2336805 60 mg + PEG + RIBA | 11 | 0 | 11 | 0 | 8 | 1 | 0 | 9 | 2 | 0 | 8 | 1 | 10 | 1 | 5 | 4 | 1 | 8 | 2 | 1 | 10 | 1 | 9 | 2 |
,| Placebo + PEG + RIBA | 2 | 1 | 3 | 1 | 1 | 1 | 1 | 3 | 0 | 1 | 1 | 1 | 4 | 0 | 4 | 0 | 0 | 4 | 0 | 0 | 3 | 0 | 4 | 0 |
Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28
Laboratory abnormalities were graded according to the modified division of AIDS ( DAIDS）version 1.0. Shift from Baseline to worst post baseline toxicity grade (where applicable) were presented for Day 1 to Day 28. The toxicity Grades were, Grade 1: mild (no or minimal interference with usual social & functional activities); Grade 2: moderate (greater than minimal interference with usual social and functional activities); Grade 3: severe (inability to perform usual social and functional activities); Grade 4: potentially life threatening (inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death). Hematology parameters were red blood cell, hemoglobin, hematocrit, platelet white blood cell count with differential leukocyte count, mean corpuscular volume, prothrombin time and international normalized ratio. (NCT01439373)
Timeframe: Baseline (Day 1) to Day 28
| Intervention | Participants (Count of Participants) |
|---|
| Hemoglobin, No toxicity | Hemoglobin, Grade 1 | Hemoglobin, Grade 2 | International normalized ratio, No toxicity | International normalized ratio, Grade 1 | Lymphocytes absolute, No toxicity | Lymphocytes absolute, Grade 4 | Platelet count, No toxicity | Platelet count, Grade 1 | Platelet count, Grade 2 | Prothrombin time, No toxicity | Prothrombin time, Grade 1 | Total neutrophils, absolute, No toxicity | Total neutrophils, absolute, Grade 1 | Total neutrophils, absolute, Grade 2 | Total neutrophils, absolute, Grade 3 | White cell count, No toxicity | White cell count, Grade 1 | White cell count, Grade 2 |
|---|
| GSK2336805 60 mg + PEG + RIBA | 7 | 3 | 1 | 10 | 1 | 10 | 1 | 10 | 1 | 0 | 10 | 1 | 7 | 1 | 2 | 1 | 8 | 2 | 1 |
,| Placebo + PEG + RIBA | 3 | 1 | 0 | 3 | 1 | 4 | 0 | 3 | 0 | 1 | 3 | 1 | 2 | 2 | 0 | 0 | 3 | 1 | 0 |
Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal
The urinalysis parameters analyzed were Leukocyte esterase, bilirubin, occult blood, glucose, ketones, nitrite, pH, specific gravity and dipstick assessments. Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important urinalysis findings at specified visit were reported. Visits where no abnormal values were observed not reported. (NCT01439373)
Timeframe: Day 14, 28, Follow-up (Day 42)
| Intervention | Participants (Count of Participants) |
|---|
| Occult blood, Day 14 | Occult blood, Follow-up | Ketone, Day 14 | Nitrate, Day 14 | Leukocytes, Day 14 |
|---|
| GSK2336805 60 mg + PEG + RIBA | 0 | 0 | 1 | 1 | 1 |
,| Placebo + PEG + RIBA | 1 | 1 | 2 | 1 | 1 |
Mean Apparent Clearance (CL/F) of GSK2336805
The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters (NCT01439373)
Timeframe: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)
| Intervention | L/h (Geometric Mean) |
|---|
| GSK2336805 60 mg | 18.27 |
Number of Participants With Vital Signs of Potential Clinical Concern
The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (<85 and >160 millimeter of mercury [mmHg]), diastolic blood pressure (<45 and >100 mmHg) and heart rate (<40 and >110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported. (NCT01439373)
Timeframe: Up to 42 days
| Intervention | Participants (Count of Participants) |
|---|
| GSK2336805 60 mg + PEG + RIBA | 0 |
| Placebo + PEG + RIBA | 0 |
Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis
The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed by nominal analysis was reported. (NCT01439373)
Timeframe: Day 28
| Intervention | Posterior probability (Mean) |
|---|
| GSK2336805 60 mg + PEG + RIBA | 0.67 |
| Placebo + PEG + RIBA | 0.21 |
Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses
The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed was reported. (NCT01439373)
Timeframe: Day 28
| Intervention | Posterior probability (Mean) |
|---|
| GSK2336805 60 mg + PEG + RIBA | 0.62 |
| Placebo + PEG + RIBA | 0.21 |
Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale
Blood samples for determination of HCV RNA levels were collected at immediately prior to and 1, 2, 4, 6, and 8 and 24 h after the first dose in Part 1 (Day 1). Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. Change from Baseline was computed as value at post Baseline specified time point minus Baseline value. Virus RNA levels reported as <43 are undetectable levels. If the result for HCV RNA (IU/ML) was <43, then change from Baseline was calculated using 42, and the change from Baseline on the log scale was calculated using log (42). (NCT01439373)
Timeframe: Day 1 (Baseline [Pre-dose], 1, 2, 4, 6, and 8 and 24 h)
| Intervention | Log IU/mL (Mean) |
|---|
| 1 h post-dose | 2 h post-dose | 4 h post-dose | 6 h post-dose | 8 h post-dose | 24 h post-dose |
|---|
| GSK2336805 60 mg (Part A) | 0.02 | -0.03 | -0.70 | -1.37 | -1.83 | -2.38 |
,| Placebo (Part A) | -0.01 | -0.00 | -0.07 | 0.08 | 0.07 | -0.11 |
Change From Baseline in QTcF Interval at Day 2 and 28
Single 12-lead electrocardiogram (ECG) was obtained. The standard ECG criteria of potential clinical importance were 1) absolute QTc Interval, > 450 milliseconds (msec), 2) absolute PR Interval, <110 msec, 3) absolute QRS Interval, < 75 msec and 4) increase from baseline in QTc > 60 msec. QTc Interval was calculated using Frederica correction formula: QTcF = QT / (RR)^1/3. Change from Baseline was calculated by subtracting the Baseline assessment value from post Baseline visit value. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. The change from Baseline in QTc Interval at Day 2 and 28 were reported. (NCT01439373)
Timeframe: Baseline (Day 1, Pre-dose ), Day 2 and Day 28
| Intervention | msec (Mean) |
|---|
| DAY 2 | DAY 28 |
|---|
| GSK2336805 60 mg + PEG + RIBA | 0.01 | -5.15 |
,| Placebo + PEG + RIBA | 0.82 | 9.13 |
Change From Baseline in Serum Alanine Aminotransferase Levels
Blood samples were collected at Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 for determination of serum alanine aminotransferase levels. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. Change from Baseline was computed as value at post Baseline specified time point minus Baseline value. (NCT01439373)
Timeframe: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42
| Intervention | Units per litre (U/L) (Mean) |
|---|
| Day 7 | Day 14 | Day 21 | Day 28 | Follow-up (Day 42) |
|---|
| GSK2336805 60 mg + PEG + RIBA | -15.3 | -25.7 | -25.9 | -24.4 | -19.5 |
,| Placebo + PEG + RIBA | -15.0 | -0.5 | -10.0 | 7.0 | -19.5 |
Mean Area Under the Concentration-time Curve (AUC[0-24]), AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK2336805, at Day 1
AUC values were determined using the linear-up, log-down trapezoidal rule. The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were below quantification limit (BLQ) before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters. (NCT01439373)
Timeframe: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2)
| Intervention | Nanogram (ng)*h/mL (Geometric Mean) |
|---|
| AUC (0-24) | AUC(0-inf) |
|---|
| GSK2336805 60 mg (Part A) | 2977.79 | 3284.90 |
Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28
Blood samples for determination of HCV RNA levels were collected from screening, immediately prior to and 1, 2, 4, 6, and 8 h after the first dose in Part 1 (Day 1), during Part 2 on Days 2 (24 h after the Day 1 dose), 7, 14, 21, and 28, and at the post-treatment follow-up visit on Day 42. All viral load samples, with the exception of the one taken during the screening visit, were taken in duplicate. The actual time and date of each sample collection will be recorded. Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test. (NCT01439373)
Timeframe: Baseline (Day 1, Pre -dose ) and Day 2 (24 h, post-dose), Day 28
| Intervention | Log IU/mL (Mean) |
|---|
| Day 2, 24 h post-dose | Day 28, Pre or Post AM dose |
|---|
| GSK2336805 60 mg + PEG + RIBA | -2.38 | -4.78 |
,| Placebo + PEG + RIBA | -0.11 | -1.99 |
Mean Maximum Plasma Concentration of GSK2336805 (Cmax) and Concentration at 24 h (C24) at Day 1
The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by non-compartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters. (NCT01439373)
Timeframe: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cmax | C24 |
|---|
| GSK2336805 60 mg (Part A) | 404.84 | 26.98 |
Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28
The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters. (NCT01439373)
Timeframe: 0 (pre-dose), 0 to 2 h, > 2 h up to 4 h, > 4 h up to 6 h, or > 6 h up to 10 h on Days 7, 14, 21 and 28
| Intervention | ng/ml (Geometric Mean) |
|---|
| Day 7, Predose | Day 7, >2 to 4 h | Day 7, >4 to 6 h | Day 14, Predose | Day 14, >0 to 2 h | Day 14, >2 to 4 h | Day 14, >4 to 6 h | Day 21, Predose | Day 21, >2 to 4 h | Day 21, >4 to 6 h | Day 21, >6 to 10 h | Day 28, Predose | Day 28, >0 to 2 h | Day 28, >2 to 4 h |
|---|
| GSK2336805 60 mg (Part A) | 37.80 | 621.40 | 314.19 | 121.57 | 518.82 | 364.75 | 304.03 | 484.18 | 346.00 | 546.72 | 317.49 | 16.95 | 607.02 | 402.05 |
Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28
Blood samples for determination of HCV RNA levels were collected from screening, immediately prior to and 1, 2, 4, 6, and 8 h after the first dose in Part 1 (Day 1), during Part 2 on Days 2 (24 h after the Day 1 dose), 7, 14, 21, and 28, and at the post-treatment follow-up visit on Day 42. All viral load samples, with the exception of the one taken during the screening visit, were taken in duplicate. The actual time and date of each sample collection will be recorded. Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test. (NCT01439373)
Timeframe: Baseline (Day 1, pre-dose), Day 2 (24 h, Post-dose) and Day 28
| Intervention | Log IU/mL (Mean) |
|---|
| Day 1, Pre-dose, | Day 2, 24 h post-dose | Day 28, Pre or Post ante meridian (AM) dose |
|---|
| GSK2336805 60 mg + PEG + RIBA | 6.61 | 4.23 | 1.80 |
,| Placebo + PEG + RIBA | 5.43 | 5.33 | 3.44 |
Participants With Change in Cough
changes in cough status after treatment for 1 month. (NCT01442779)
Timeframe: 1 month
| Intervention | Participants (Number) |
|---|
| Interferon Alpha | 5 |
Minimal/no Progression (1 yr) by High Resolution Computed Tomography (HRCT) & Pulmonary Function
Disease progression was determined by comparing results of the High Resolution Computed Tomography(HRCT) and pulmonary function at one year to the baseline HRCT & pulmonary function. The same radiologist did the comparsion for all subjects. (NCT01442779)
Timeframe: 1 yr
| Intervention | Participants (Number) |
|---|
| Interferon Alpha | 12 |
Minimal/no Change in Quality of Life
(NCT01442779)
Timeframe: 12 months
| Intervention | Participants (Number) |
|---|
| Interferon Alpha | 12 |
Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) or Sustained Virologic Response at Follow-up Week 24 (SVR24) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene
Participants categorized into three genotypes based on SNPs in the IL28B gene were assessed for SVR12 and SVR24, defined as response in which hepatitis C virus RNA levels below lower limit of quantitation or below target detected or target not detected at follow-up Week 12 and Week 24 respectively. (NCT01448044)
Timeframe: Post Treatment Weeks 12, 24
| Intervention | Percentage of participants (Number) |
|---|
| IL28B Genotype CC (SVR12) (n=22, 9) | IL28B Genotype CT (SVR12) (n=40, 27) | IL28B Genotype TT (SVR12) (n=20, 6) | IL28B Genotype CC (SVR24) (n=22, 9) | IL28B Genotype CT (SVR24) (n=40, 27) | IL28B Genotype TT (SVR24) (n=20, 6) |
|---|
| Daclatasvir + PegIFNα2a + Ribavirin | 95.5 | 75.0 | 80.0 | 95.5 | 72.5 | 80.0 |
,| Placebo + PegIFNα2a + Ribavirin | 100.0 | 33.3 | 0.0 | 88.9 | 33.3 | 0.0 |
Percentage of Participants With Undetectable Hepatitis C Virus (HCV) RNA Levels
Participants who achieved HCV RNA undetectable ie, 10 international units per milliliter (IU/mL). Participants in the placebo arm did not have visits beyond post treatment Week 24. (NCT01448044)
Timeframe: Treatment Weeks 1, 2, 4, 6, 8 and 12; Weeks 4 and 12, End of treatment (EOT), Post treatment Week 24, Post treatment Week 48
| Intervention | Percentage of participants (Number) |
|---|
| Week 1 | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Weeks 4 and 12 (VR 4 & 12) | EOT | Post treatment Week 24 | Post treatment Week 48 |
|---|
| Daclatasvir + PegIFNα2a + Ribavirin | 14.6 | 45.1 | 85.4 | 80.5 | 87.8 | 84.1 | 79.3 | 90.2 | 78.0 | 81.8 |
,| Placebo + PegIFNα2a + Ribavirin | 0.0 | 9.5 | 11.9 | 16.7 | 38.1 | 47.6 | 11.9 | 64.3 | 40.5 | NA |
Percentage of Participants Who Achieve HCV Ribonucleic Acid (RNA) < Limit of Quantification (LLOQ)
Participants who achieved HCV RNA levels below LLOQ ie, 25 international unit per milliliter (IU/mL). Participants in the placebo arm did not have visits beyond post treatment Week 24. (NCT01448044)
Timeframe: Treatment Weeks 1, 2, 4, 6, 8 and 12; Weeks 4 and 12; End of treatment (EOT); Post treatment Week 24; Post treatment Week 48
| Intervention | Percentage of participants (Number) |
|---|
| Week 1 | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Weeks 4 and 12 | End of Treatment | Post treatment Week 24 | Post treatment Week 48 |
|---|
| Daclatasvir + PegIFNα2a + Ribavirin | 53.7 | 89.0 | 91.5 | 84.1 | 87.8 | 85.4 | 84.1 | 92.7 | 80.5 | 83.6 |
,| Placebo + PegIFNα2a + Ribavirin | 4.8 | 11.9 | 19.0 | 40.5 | 47.6 | 59.5 | 19.0 | 64.3 | 40.5 | NA |
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalisation. (NCT01448044)
Timeframe: From Day 1 (start of study treatment) up to Follow-up Week 4
| Intervention | participants (Number) |
|---|
| AEs leading to discontinuation of study drug | SAEs | Death |
|---|
| Daclatasvir + PegIFNα2a + Ribavirin | 4 | 8 | 0 |
,| Placebo + PegIFNα2a + Ribavirin | 3 | 2 | 0 |
Percentage of Participants With 12 Week Sustained Virologic Response (SVR12)
Participants were assessed for sustained virologic response 12 weeks post treatment (SVR12) defined as hepatitis C virus (HCV) RNA levels < lower limit of quantitation (LLOQ was 25 IU/mL), target detected (TD) or target not detected (TND) at post-treatment Week 12. (NCT01448044)
Timeframe: Week 12 (Follow-up period)
| Intervention | Percentage of participants (Number) |
|---|
| Daclatasvir + PegIFNα2a + Ribavirin | 81.7 |
| Placebo + PegIFNα2a + Ribavirin | 42.9 |
Number of Subjects With Extended Rapid Viral Response (eRVR)
"The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. eRVR was defined as undetectable HCV RNA at both 4 weeks and 12 weeks after the start of study treatment. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups." (NCT01459913)
Timeframe: Week 4 and Week 12
| Intervention | participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) | 105 |
| Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) | 51 |
Percentage of Subjects With Sustained Viral Response 4 Weeks After Last Planned Dose of Study Drug (SVR4)
"SVR4 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at 4 weeks after last planned dose of study treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups." (NCT01459913)
Timeframe: 4 weeks after last planned dose of study drug (up to Week 28)
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) | 89.6 |
| Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) | 98.1 |
Percentage of Subjects With Viral Relapse
"Viral relapse was defined as having detectable HCV RNA during antiviral follow-up in subjects who had HCV RNA less than (<) lower limit of quantification (LLOQ) at end of treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The LLOQ was 25 IU/mL and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups." (NCT01459913)
Timeframe: After last dose of study drug up to 4 weeks (up to Week 28), 12 weeks (up to Week 36), 24 weeks (up to Week 48) antiviral follow-up
| Intervention | percentage of participants (Number) |
|---|
| 4 Weeks | 12 Weeks | 24 Weeks |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) | 1.9 | 7.5 | 10.4 |
,| Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) | 0.0 | 0.0 | 0.0 |
Percentage of Subjects With Sustained Viral Response at Week 72 (SVR72)
"SVR72 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Week 72. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups." (NCT01459913)
Timeframe: Week 72
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) | 72.4 |
| Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) | 86.5 |
Percentage of Subjects With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)
"SVR12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at 12 weeks after last planned dose of study drug. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups." (NCT01459913)
Timeframe: 12 weeks after last planned dose of study drug (up to Week 36)
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) | 88.7 |
| Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) | 96.2 |
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
"AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Study drug includes all investigational agents administered during the course of the study." (NCT01459913)
Timeframe: Baseline up to Week 48
| Intervention | participants (Number) |
|---|
| AEs | SAEs |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) | 104 | 5 |
,| Telaprevir 12 Wk +Peg-IFN-alfa-2a,RBV 48 Wk (Non Randomized) | 61 | 13 |
,| Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Non Randomized) | 19 | 3 |
,| Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) | 51 | 4 |
Number of Subjects With Rapid Viral Response (RVR)
"The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. RVR was defined as undetectable HCV RNA 4 weeks after the start of study treatment. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups." (NCT01459913)
Timeframe: Week 4
| Intervention | participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) | 106 |
| Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) | 52 |
Percentage of Subjects With On-Treatment Virologic Failure
On-treatment virologic failure was defined as subjects who met futility (as per investigator discretion) or who completed the assigned treatment duration and had detectable HCV RNA at planned end of treatment (up to 48 weeks). This outcome was planned to be assessed in all reporting groups and results were to be reported for total arm as well. (NCT01459913)
Timeframe: Baseline up to Week 48
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) | 0 |
| Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) | 0 |
| Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Non Randomized) | 0 |
| Telaprevir 12 Wk +Peg-IFN-alfa-2a,RBV 48 Wk (Non Randomized) | 3.3 |
| Telaprevir+Peg-IFN-alfa-2a, RBV (Total) | 0.8 |
Percentage of Subjects With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24)
"SVR24 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at 24 weeks after last planned dose of study treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups." (NCT01459913)
Timeframe: 24 weeks after last planned dose of study drug (up to Week 48)
| Intervention | percentage of participants (Number) |
|---|
| Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) | 85.8 |
| Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) | 92.3 |
Level of Activated STAT1(Phospho-STAT1)
Mean and 95% confidence interval will be summarized for phospho-STAT1 at a lower dose and the standard dose. The phospho-STAT1 will also be compared between the dose levels. (NCT01460875)
Timeframe: up to 4 weeks
| Intervention | MU/m2 (Mean) |
|---|
| Dose I (10 MU/m2) | Dose II (4 MU/m2) |
|---|
| Treatment (Interferon Therapy) | 5.96 | 4.80 |
Effect of Dose-reduction on Interferon Alfa Gene Expression at Dose Level 4MU
Evaluated using microarray analysis of patient PBMCs. Compared between doses using the Wilcoxon signed rank test. (NCT01460875)
Timeframe: 4 hours post therapy
| Intervention | fold increase (Median) |
|---|
| SOCS1-4 hour post 4MU- | OAS1-4 hour post 4MU | CXCL10-4 hour post 4MU | CD69-4 hour post 4MU |
|---|
| Treatment (Interferon Therapy) | 1.6 | 3.9 | 112.9 | 1.5 |
Effect of Dose-reduction on Expression of Interferon Alfa Stimulated Genes
Evaluated using microarray analysis of patient PBMCs. Compared using the Wilcoxon signed rank test for the dose 10MU/m2 (NCT01460875)
Timeframe: 1 hour post therapy
| Intervention | fold change (Median) |
|---|
| SOCS1-1 hour post 10MU- | OAS1-1 hour post 10MU- | CXCL10-1 hour post 10MU | CD69-1 hour post 10MU |
|---|
| Treatment (Interferon Therapy) | 1.5 | 1.6 | 28.7 | 1.3 |
Effect of Dose-reduction on Interferon Alfa Gene Expression
Evaluated using microarray analysis of patient PBMCs. Compared using the Wilcoxon signed rank test for the dose 4MU/m2 (NCT01460875)
Timeframe: 1 hour post therapy
| Intervention | fold increase (Median) |
|---|
| SOCS1-1 hour post 4MU | OAS1-1 hour post 4MU | CXCL10-1 hour post 4MU | CD69-1 hour post 4MU |
|---|
| Treatment (Interferon Therapy) | 1.2 | 1.6 | 6.0 | 1.3 |
Effect of Dose-reduction on Interferon Alfa Gene Expression Through Marker CD69
Evaluated using microarray analysis of patient PBMCs. Compared between doses using the Wilcoxon signed rank test. (NCT01460875)
Timeframe: 4 hours post therapy
| Intervention | fold increase (Median) |
|---|
| SOCS1- 4 hour post-10MU | OAS1-4 hour post -10MU | CXCL10-4 hour post- 10MU | CD69-4 hour post- 10MU |
|---|
| Treatment (Interferon Therapy) | 1.5 | 1.6 | 28.7 | 1.3 |
Number of Patients With Adverse Events
Determine the tolerability of adjuvant IFN-α-2b administered at an optimized dose in terms of the toxicities that are observed and the ability of patients to receive a full year of therapy. (NCT01460875)
Timeframe: up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Interferon Therapy) | 15 |
Percentage of Patients With Correlation Between STAT1 Phosphorylation and Interferon Alfa Gene Regulation
Levels of p-STAT1 in PBMCs were analyzed just prior to IFN-a-2b administration to determine levels that remained stable or increased over the course of dose reduction. (NCT01460875)
Timeframe: Prior to treatment and 1 and 4 hours post therapy on day 1 every other week during the first 12 weeks, and then every 3 months
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Interferon Therapy) | 71 |
Document Any Objective Anti-tumor Responses and Time to Tumor Progression That May Occur in Response to This Treatment Regimen.
"Measure levels of the cell cycle proteins p21 and p27 in PBMCs and tumor biopsies obtained pre-study and during week 4 of Cycle 1 (Day 26).~Conduct histologic evaluations of microvessel density, tumor apoptosis and lymphocytic infiltrates within tumor biopsies obtained pre- and post-study.~Measure plasma levels of bFGF and VEGF over the course of the study.~Monitor the effects of proteasome inhibition on the biological activity of IFN-α within immune cells by measuring Jak-STAT signal transduction in patient PBMCs." (NCT01462773)
Timeframe: up to 25 weeks
| Intervention | patients (Number) |
|---|
| partial response | stable disease |
|---|
| Bortezomib & Interferon-a | 1 | 7 |
Percentage of Participants With Undetectable HCV RNA at End of Treatment (EOT)
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. Percentage of participants with undetectable HCV RNA (NCT01467479)
Timeframe: EOT (up to Week 48)
| Intervention | percentage of participants (Number) |
|---|
| T/PR + HAART Regimen (ATV/r-Based) | 55.6 |
| T/PR + HAART Regimen (EFV-Based) | 63.8 |
| T/PR + HAART Regimen (RAL-Based) | 61.0 |
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24)
SVR 24 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (NCT01467479)
Timeframe: 24 weeks after last planned dose of study drug (up to Week 72)
| Intervention | percentage of participants (Number) |
|---|
| Treatment Naïve (n= 23, 38, 29) | Prior Relapser (n=8, 11, 4) | Prior Null Responder (n= 15, 9, 14) | Prior Partial Responder (n= 7, 8, 9) | Total (n= 53, 66, 56) |
|---|
| T/PR + HAART Regimen (ATV/r-Based) | 65.2 | 75.0 | 33.3 | 14.3 | 50.9 |
,| T/PR + HAART Regimen (EFV-Based) | 57.9 | 54.5 | 22.2 | 75.0 | 54.5 |
,| T/PR + HAART Regimen (RAL-Based) | 51.7 | 100 | 35.7 | 55.6 | 51.8 |
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)
SVR 12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (NCT01467479)
Timeframe: 12 weeks after last planned dose of study drug (up to Week 60)
| Intervention | percentage of participants (Number) |
|---|
| Treatment Naïve (n= 24, 39, 31) | Prior Relapser (n=8, 11, 4) | Prior Null Responder (n= 15, 11, 15) | Prior Partial Responder (n= 7, 8, 9) | Total (n= 54, 69, 59) |
|---|
| T/PR + HAART Regimen (ATV/r-Based) | 66.7 | 75.0 | 40 | 14.3 | 53.7 |
,| T/PR + HAART Regimen (EFV-Based) | 59.0 | 54.5 | 36.4 | 87.5 | 58.0 |
,| T/PR + HAART Regimen (RAL-Based) | 61.3 | 100 | 40 | 55.6 | 57.6 |
Percentage of Participants With Rapid Viral Response (RVR)
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. RVR was defined as undetectable HCV RNA (NCT01467479)
Timeframe: Week 4
| Intervention | percentage of participants (Number) |
|---|
| Treatment Naïve (n= 24, 39, 31) | Prior Relapser (n=8, 11, 4) | Prior Null Responder (n= 15, 11, 15) | Prior Partial Responder (n= 7, 8, 9) | Total (n= 54, 69, 59) |
|---|
| T/PR + HAART Regimen (ATV/r-Based) | 50.0 | 62.5 | 26.7 | 42.9 | 44.4 |
,| T/PR + HAART Regimen (EFV-Based) | 53.8 | 72.7 | 54.5 | 50.0 | 56.5 |
,| T/PR + HAART Regimen (RAL-Based) | 74.2 | 100 | 53.3 | 44.4 | 66.1 |
Percentage of Participants With Extended Rapid Viral Response (eRVR)
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. eRVR was defined as undetectable HCV RNA (NCT01467479)
Timeframe: Week 4 and Week 12
| Intervention | percentage of participants (Number) |
|---|
| Treatment Naïve (n= 24, 39, 31) | Prior Relapser (n=8, 11, 4) | Prior Null Responder (n= 15, 11, 15) | Prior Partial Responder (n= 7, 8, 9) | Total (n= 54, 69, 59) |
|---|
| T/PR + HAART Regimen (ATV/r-Based) | 50.0 | 62.5 | 26.7 | 14.3 | 40.7 |
,| T/PR + HAART Regimen (EFV-Based) | 53.8 | 72.7 | 54.5 | 50.0 | 56.5 |
,| T/PR + HAART Regimen (RAL-Based) | 61.3 | 100 | 53.3 | 44.4 | 59.3 |
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. (NCT01467479)
Timeframe: Up to Week 52
| Intervention | percentage of participants (Number) |
|---|
| AEs | SAEs |
|---|
| T/PR + HAART Regimen (ATV/r-Based) | 100 | 13.0 |
,| T/PR + HAART Regimen (EFV-Based) | 95.7 | 11.6 |
,| T/PR + HAART Regimen (RAL-Based) | 94.9 | 15.3 |
Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region
Sequence analysis of the HCV NS3-4A region was performed to monitor telaprevir-resistant variants. HCV RNA was isolated from the plasma, amplified by reverse transcription-polymerase chain reaction (RT-PCR), and sequenced (sequencing assay limit of detection HCV RNA >=1000 IU/mL). Results of this outcome measure were to be reported for overall participants instead of by HAART treatment. (NCT01467479)
Timeframe: Baseline, follow-up (Week 96)
| Intervention | participants (Number) |
|---|
| Baseline (n = 180) | Follow-up (n = 26) |
|---|
| T/PR + HAART Regimen | 2 | 11 |
Maximum (Cmax), Minimum (Cmin), and Average Plasma Concentration (Cavg)
Cmax, Cmin, and Cavg were reported for atazanavir (ATV), efavirenz (EFV), raltegravir (RAL), and telaprevir. (NCT01467479)
Timeframe: Day -14 to Day -1 and Week 1 for ATV, EFV, and RAL; Week 1 for telaprevir
| Intervention | nanogram per milliliter (ng/mL) (Mean) |
|---|
| ATV: Day -14 to Day -1, Cmax(n=46, 0, 0) | ATV: Day -14 to Day -1, Cmin(n=46, 0, 0) | ATV: Day -14 to Day -1, Cavg(n=41, 0, 0) | ATV: Week 1, Cmax (n=42, 0, 0) | ATV: Week 1, Cmin (n=42, 0, 0) | ATV: Week 1, Cavg (n=30, 0, 0) | EFV: Day -14 to Day -1, Cmax(n=0, 60, 0) | EFV: Day -14 to Day -1, Cmin(n=0, 60, 0) | EFV: Day -14 to Day -1, Cavg(n=0, 51, 0) | EFV: Week 1, Cmax (n=0, 51, 0) | EFV: Week 1, Cmin (n=0, 51, 0) | EFV: Week 1, Cavg (n=0, 47, 0) | RAL: Day -14 to Day -1, Cmax(n=0, 0, 52) | RAL: Day -14 to Day -1, Cmin(n=0, 0, 52) | RAL: Day -14 to Day -1, Cavg(n=0, 0, 35) | RAL: Week 1, Cmax (n=0, 0, 49) | RAL: Week 1, Cmin (n=0, 0, 49) | RAL: Week 1, Cavg (n=0, 0, 34) | Telaprevir: Week 1, Cmax(n=49, 59, 54) | Telaprevir: Week 1, Cmin(n=49, 59, 54) | Telaprevir: Week 1, Cavg(n=30, 32, 26) |
|---|
| T/PR + HAART Regimen (ATV/r-Based) | 2870 | 991 | 1100 | 2820 | 1280 | 1320 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | 3160 | 1650 | 2320 |
,| T/PR + HAART Regimen (EFV-Based) | NA | NA | NA | NA | NA | NA | 3800 | 2560 | 2150 | 3340 | 2290 | 1920 | NA | NA | NA | NA | NA | NA | 3780 | 1750 | 2430 |
,| T/PR + HAART Regimen (RAL-Based) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | 1900 | 196 | 483 | 2320 | 281 | 643 | 3470 | 1840 | 2520 |
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes SAE as well as Non-SAEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. (NCT01467492)
Timeframe: Up to Week 52
| Intervention | percentage of participants (Number) |
|---|
| AE | SAE |
|---|
| Group A - Black | 96.3 | 8.5 |
,| Group B - Non-Black | 100.0 | 15.8 |
Percentage of Participants With Extended Rapid Viral Response (eRVR)
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. eRVR was defined as undetectable HCV RNA (NCT01467492)
Timeframe: Week 4 and Week 12
| Intervention | percentage of participants (Number) |
|---|
| Prior Null Response (n = 41, 10) | Prior Partial Response (n= 20, 6) | Prior Relapse ( n= 21, 22) | Total (n= 82, 38) |
|---|
| Group A - Black | 24.4 | 45.0 | 66.7 | 40.2 |
,| Group B - Non-Black | 30.0 | 66.7 | 68.2 | 57.9 |
Percentage of Participants With On Treatment Virologic Failure
On treatment virologic failure was defined as meeting any futility rule or completing assigned treatment duration and having detectable HCV RNA at EOT. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. Futility rules: 1) Virologic breakthrough (at least 1 log10 increase from nadir or confirmed detectable HCV RNA after undetectable HCV RNA) from Day 1 through Week 24 or 48 (depending on treatment duration); 2) HCV RNA >1000 IU/mL during Weeks 4 to 12, inclusive; 3) Detectable HCV RNA after Week 12. Percentages are calculated by using total number in FA set as denominator, in each category. (NCT01467492)
Timeframe: Week 2, 4, 8, 12, 16, 24, 28, 36, 40, and 48
| Intervention | percentage of participants (Number) |
|---|
| Prior Null Response, Week 2 | Prior Null Response, Week 4 | Prior Null Response, Week 8 | Prior Null Response, Week 12 | Prior Null Response, Week 16 | Prior Null Response, Week 24 | Prior Null Response, Week 28 | Prior Null Response, Week 36 | Prior Null Response, Week 40 | Prior Null Response, Week 48 | Prior Partial Response, Week 2 | Prior Partial Response, Week 4 | Prior Partial Response, Week 8 | Prior Partial Response, Week 12 | Prior Partial Response, Week 16 | Prior Partial Response, Week 24 | Prior Partial Response, Week 28 | Prior Partial Response, Week 36 | Prior Partial Response, Week 40 | Prior Partial Response, Week 48 | Prior Relapse, Week 2 | Prior Relapse, Week 4 | Prior Relapse, Week 8 | Prior Relapse, Week 12 | Prior Relapse, Week 16 | Prior Relapse, Week 24 | Prior Relapse, Week 28 | Prior Relapse, Week 36 | Prior Relapse, Week 40 | Prior Relapse, Week 48 | Total, Week 2 | Total, Week 4 | Total, Week 8 | Total, Week 12 | Total, Week 16 | Total, Week 24 | Total, Week 28 | Total, Week 36 | Total, Week 40 | Total, Week 48 |
|---|
| Group A - Black | 0 | 4.9 | 8.5 | 12.2 | 19.5 | 23.2 | 23.2 | 25.6 | 28.0 | 29.3 | 0 | 2.4 | 2.4 | 4.9 | 4.9 | 6.1 | 6.1 | 7.3 | 7.3 | 7.3 | 0 | 0 | 0 | 1.2 | 1.2 | 1.2 | 1.2 | 1.2 | 1.2 | 1.2 | 0 | 7.3 | 11.0 | 18.3 | 25.6 | 30.5 | 30.5 | 34.1 | 36.6 | 37.8 |
,| Group B - Non-Black | 0 | 2.6 | 7.9 | 7.9 | 7.9 | 10.5 | 13.2 | 13.2 | 13.2 | 13.2 | 0 | 0 | 0 | 0 | 2.6 | 7.9 | 10.5 | 10.5 | 10.5 | 10.5 | 0 | 0 | 0 | 0 | 0 | 2.6 | 2.6 | 2.6 | 5.3 | 5.3 | 0 | 2.6 | 7.9 | 7.9 | 10.5 | 21.1 | 26.3 | 26.3 | 28.9 | 28.9 |
Percentage of Participants With Relapse
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. Relapse was defined as having undetectable HCV RNA (=lower limit of quantification) during follow-up. (NCT01467492)
Timeframe: 4 weeks (Wk) (up to Week 52), 12 weeks (up to Week 60) and 24 weeks (up to Week 72) after actual EOT
| Intervention | percentage of participants (Number) |
|---|
| Prior Null Response, 4 Wk After EOT (n=17,3) | Prior Null Response, 12 Wk After EOT (n=17,3) | Prior Null Response, 24 Wk After EOT (n=17,3) | Prior Partial Response, 4Wk After EOT (n=13,4) | Prior Partial Response, 12 Wk After EOT (n=13,4) | Prior Partial Response, 24 Wk After EOT (n=13,4) | Prior Relapse, 4 Wk After EOT (n=18,19) | Prior Relapse, 12 Wk After EOT (n=18,19) | Prior Relapse, 24 Wk After EOT (n=18,19) | Total, 4 Wk After EOT (n=48,26) | Total, 12 Wk After EOT (n=48,26) | Total, 24 Wk After EOT (n=48,26) |
|---|
| Group A - Black | 23.5 | 23.5 | 29.4 | 15.4 | 23.1 | 23.1 | 11.1 | 11.1 | 11.1 | 16.7 | 18.8 | 20.8 |
,| Group B - Non-Black | 33.3 | 33.3 | 33.3 | 50.0 | 50.0 | 50.0 | 15.8 | 26.3 | 26.3 | 23.1 | 30.8 | 30.8 |
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Actual Dose of Study Drug (SVR12)
SVR12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (NCT01467492)
Timeframe: 12 weeks after last actual dose of study drug (up to Week 60)
| Intervention | percentage of participants (Number) |
|---|
| Prior Null Response (n = 41, 10) | Prior Partial Response (n= 20, 6) | Prior Relapse ( n= 21, 22) | Total (n= 82, 38) |
|---|
| Group A - Black | 26.8 | 40.0 | 66.7 | 40.2 |
,| Group B - Non-Black | 20.0 | 33.3 | 59.1 | 44.7 |
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Actual Dose of Study Drug (SVR24)
SVR24 was defined as an undetectable HCV RNA Levels (NCT01467492)
Timeframe: 24 weeks after last actual dose of study drug (up to Week 72)
| Intervention | percentage of participants (Number) |
|---|
| Prior Null Response (n = 41, 10) | Prior Partial Response (n= 20, 6) | Prior Relapse ( n= 21, 22) | Total (n= 82, 38) |
|---|
| Group A - Black | 19.5 | 30.0 | 61.9 | 32.9 |
,| Group B - Non-Black | 20.0 | 16.7 | 50.0 | 36.8 |
Percentage of Participants With Virologic Breakthrough
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. Virologic breakthrough on treatment was defined as an increase of at least 1 log10 from nadir or confirmed detectable HCV RNA (>=lower limit of quantification) after undetectable HCV RNA (NCT01467492)
Timeframe: Week 2, 4, 8, and 12
| Intervention | percentage of participants (Number) |
|---|
| Prior Null Response, Week 2 | Prior Null Response, Week 4 | Prior Null Response, Week 8 | Prior Null Response, Week 12 | Prior Partial Response, Week 2 | Prior Partial Response, Week 4 | Prior Partial Response, Week 8 | Prior Partial Response, Week 12 | Prior Relapse, Week 2 | Prior Relapse, Week 4 | Prior Relapse, Week 8 | Prior Relapse, Week 12 | Total, Week 2 | Total, Week 4 | Total, Week 8 | Total, Week 12 |
|---|
| Group A - Black | 0 | 1.2 | 3.7 | 6.1 | 0 | 2.4 | 2.4 | 2.4 | 0 | 0 | 0 | 1.2 | 0 | 3.7 | 3.7 | 9.8 |
,| Group B - Non-Black | 0 | 2.6 | 5.3 | 5.3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2.6 | 5.3 | 5.3 |
Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region
Sequence analysis of the HCV NS3-4A region was performed to monitor telaprevir-resistant variants. HCV RNA was isolated from the plasma, amplified by reverse transcription-polymerase chain reaction (RT-PCR), and sequenced (sequencing assay limit of detection HCV RNA >=1000 IU/mL). Results of this outcome measure were to be reported for overall participants instead of by race and by prior response. (NCT01467492)
Timeframe: up to Week 72
| Intervention | participants (Number) |
|---|
| All Participants | 47 |
Percentage of Participants With Extended Rapid Viral Response (eRVR)
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. eRVR was defined as undetectable HCV RNA at both 4 weeks and 12 weeks after the start of study treatment. (NCT01467505)
Timeframe: Week 4 and Week 12
| Intervention | percentage of participants (Number) |
|---|
| Naive (n= 16, 2) | Prior Relapser (n= 10, 2) | Prior Null Responder (n=16, 4) | Prior Partial Responder (n= 3, 1) | Uncategorized (n= 6, 1) | Total (n= 51, 10) |
|---|
| T/PR + Immunosuppressant Regimen (Cyclosporine) | 0 | 50.0 | 25.0 | 100.0 | 0 | 30.0 |
,| T/PR + Immunosuppressant Regimen (Tacrolimus) | 68.8 | 50.0 | 37.5 | 66.7 | 33.3 | 51.0 |
Percentage of Participants With Rapid Viral Response (RVR)
The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. RVR was defined as undetectable HCV RNA 4 weeks after the start of study treatment. (NCT01467505)
Timeframe: Week 4
| Intervention | percentage of participants (Number) |
|---|
| Naive (n= 16, 2) | Prior Relapser (n= 10, 2) | Prior Null Responder (n=16, 4) | Prior Partial Responder (n= 3, 1) | Uncategorized (n= 6, 1) | Total (n= 51, 10) |
|---|
| T/PR + Immunosuppressant Regimen (Cyclosporine) | 0 | 50.0 | 25.0 | 100.0 | 0 | 30.0 |
,| T/PR + Immunosuppressant Regimen (Tacrolimus) | 68.8 | 50.0 | 43.8 | 66.7 | 33.3 | 52.9 |
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)
SVR12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (NCT01467505)
Timeframe: 12 weeks after last planned dose of study drug (up to Week 60)
| Intervention | percentage of participants (Number) |
|---|
| Naive (n= 16, 2) | Prior Relapser (n= 10, 2) | Prior Null Responder (n=16, 4) | Prior Partial Responder (n= 3, 1) | Uncategorized (n= 6, 1) | Total (n= 51, 10) |
|---|
| T/PR + Immunosuppressant Regimen (Cyclosporine) | 50.0 | 100.0 | 50.0 | 100.0 | 100.0 | 70.0 |
,| T/PR + Immunosuppressant Regimen (Tacrolimus) | 75.0 | 60.0 | 37.5 | 66.7 | 50.0 | 56.9 |
Percentage of Participants With On-Treatment Virologic Failure
On-treatment virologic failure was defined as subjects who met futility or who completed the assigned treatment duration and had detectable HCV RNA at planned end of treatment (up to 48 weeks). Data for this outcome was not planned to be reported by prior response. (NCT01467505)
Timeframe: Baseline up to Week 48
| Intervention | percentage of participants (Number) |
|---|
| T/PR + Immunosuppressant Regimen (Tacrolimus) | 0 |
| T/PR + Immunosuppressant Regimen (Cyclosporine) | 0 |
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24)
SVR24 was defined as an undetectable HCV RNA Levels at 24 weeks after last planned dose of study treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. (NCT01467505)
Timeframe: 24 weeks after last planned dose of study drug (up to Week 72)
| Intervention | percentage of participants (Number) |
|---|
| Naive (n= 5,1) | Prior Relapser (n= 4,1) | Prior Null Responder (n=10, 4) | Prior Partial Responder (n= 0, 1) | Uncategorized (n= 5, 0) | Total (n= 24, 7) |
|---|
| T/PR + Immunosuppressant Regimen (Cyclosporine) | 0 | 0 | 50.0 | 100.0 | 0 | 42.9 |
,| T/PR + Immunosuppressant Regimen (Tacrolimus) | 60.0 | 25.0 | 20.0 | 0 | 20.0 | 29.2 |
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
"Any adverse change from the participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Study drug includes all investigational agents (including placebo, if applicable) administered during the course of the study." (NCT01467505)
Timeframe: Baseline up to Week 52
| Intervention | participants (Number) |
|---|
| AEs | SAEs |
|---|
| T/PR + Immunosuppressant Regimen (Cyclosporine) | 10 | 3 |
,| T/PR + Immunosuppressant Regimen (Tacrolimus) | 51 | 11 |
Changes in Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week 48 Compared to Baseline
"Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.~A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome." (NCT01468337)
Timeframe: Baseline and Week 48
| Intervention | ETDRS letters (Mean) |
|---|
| Interferon Gamma-1b | 4.67 |
Changes in Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week 2 Compared to Baseline
"Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.~A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome." (NCT01468337)
Timeframe: Baseline and Week 2
| Intervention | ETDRS letters (Mean) |
|---|
| Interferon Gamma-1b | 0.80 |
Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 2 Compared to Baseline
"Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.~A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome." (NCT01468337)
Timeframe: Baseline and Week 2
| Intervention | ETDRS letters (Mean) |
|---|
| Interferon Gamma-1b | 0.4 |
Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 48 Compared to Baseline
"Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.~A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome." (NCT01468337)
Timeframe: Baseline and Week 48
| Intervention | ETDRS letters (Mean) |
|---|
| Interferon Gamma-1b | 2.67 |
Number of Participants Who Withdrew From the Study
(NCT01468337)
Timeframe: Week 48
| Intervention | participants (Number) |
|---|
| Interferon Gamma-1b | 0 |
Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene
Percentages calculated as number of responders/number who received treatment. (NCT01471574)
Timeframe: Follow-up Week 12
| Intervention | Percentage of participants (Number) |
|---|
| CC Genotype (n=36, 14, 39, 89, 6) | CT Genotype (n=72, 22, 50,144, 15) | TT Genotype (n=22, 3, 12, 37, 2) | Not reported (n=2, 0, 5, 7, 1) |
|---|
| HAART Therapy: Daclatasvir 30, 60 or 90 mg | 87.6 | 67.4 | 62.2 | 71.4 |
,| HAART Therapy: Daclatasvir, 30 mg + 60 mg | 79.5 | 70.0 | 58.3 | 60.0 |
,| HAART Therapy: Daclatasvir, 60 mg | 92.9 | 63.6 | 33.3 | 0.0 |
,| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | 94.4 | 66.7 | 68.2 | 100.0 |
,| Non-HAART Therapy: Daclatasvir, 60 mg | 100.0 | 93.3 | 50.0 | 0.0 |
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND)
Participants who achieved HCV RNA levels lower than the LLOQ i.e., 25 IU/ml, TD or TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. (NCT01471574)
Timeframe: Week 1, 2, 4, 6, 8, 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24
| Intervention | Percentage of participants (Number) |
|---|
| Week 1 | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Weeks 4 and 12 | End of treatment | Follow-up Week 12 | Follow-up Week 24 |
|---|
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | 39.7 | 71.5 | 82.7 | 84.1 | 84.1 | 85.2 | 78.7 | 84.8 | 73.3 | 70.4 |
,| Non-HAART Therapy: Daclatasvir, 60 mg | 41.7 | 91.7 | 95.8 | 87.5 | 95.8 | 91.7 | 91.7 | 95.8 | 87.5 | 83.3 |
Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation
Adverse event was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threating, an important medical event, or a congenital anomaly/birth defect; or required prolonged hospitalization. HAART=highly active antiretroviral therapy. (NCT01471574)
Timeframe: From Day 1 to 7 days post last dose of study treatment (up to Week 48)
| Intervention | Participants (Number) |
|---|
| Deaths | SAEs | Grade 3 to 4 AEs | AEs leading to discontinuation |
|---|
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | 2 | 24 | 93 | 17 |
,| HAART Therapy: Daclatasvir, 30 mg + 60 mg | 0 | 6 | 35 | 6 |
,| HAART Therapy: Daclatasvir, 60 mg | 1 | 6 | 12 | 4 |
,| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | 0 | 12 | 46 | 7 |
,| Non-HAART Therapy: Daclatasvir, 60 mg | 0 | 0 | 4 | 1 |
Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)
SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. (NCT01471574)
Timeframe: Follow-up Week 12
| Intervention | Percentage of participants (Number) |
|---|
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | 75 |
| HAART Therapy: Daclatasvir, 60 mg | 71.8 |
| HAART: Daclatasvir, 30 mg + 60 mg | 71.7 |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | 73.3 |
| Non-HAART Therapy: Daclatasvir, 60 mg | 87.5 |
Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL
Participants who received HAART, maintained HIV RNA <40 copies/mL, and experienced confirmed HIV RNA ≥ 400 copies/mL were determined. (NCT01471574)
Timeframe: End of treatment (up to Week 48)
| Intervention | Percentage of participants (Number) |
|---|
| HIV RNA <40 copies/mL | HIV RNA ≥400 copies/mL |
|---|
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | 90.6 | 0.4 |
,| HAART Therapy: Daclatasvir, 30mg + 60 mg | 93.4 | 0.0 |
,| HAART Therapy: Daclatasvir, 60 mg | 89.7 | 2.6 |
,| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | 88.6 | 0.0 |
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND)
Participants who achieved HCV RNA levels lower than the LLOQ, TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. (NCT01471574)
Timeframe: Week 1, 2, 4, 6, 8, and 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24
| Intervention | Percentage of participants (Number) |
|---|
| Week 1 | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Weeks 4 and 12 | End of treatment | Follow-up Week 12 | Follow-up Week 24 |
|---|
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | 9 | 33.9 | 64.3 | 74.4 | 78 | 81.2 | 61.4 | 84.8 | 73.3 | 70.4 |
,| Non-HAART Therapy: Daclatasvir, 60 mg | 16.7 | 50 | 91.7 | 87.5 | 95.8 | 91.7 | 87.5 | 95.8 | 87.5 | 83.3 |
Change From Baseline in CD4+ Cell Count in Percentage
(NCT01479868)
Timeframe: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
| Intervention | percentage of lymphocyte (Mean) |
|---|
| Baseline (n=93) | Change at Week 2 (n=89) | Change at Week 4 (n=91) | Change at Week 8 (n=92) | Change at Week 12 (n=91) | Change at Week 16 (n=88) | Change at Week 20 (n=84) | Change at Week 24 (n=89) | Change at Week 28 (n=82) | Change at Week 36 (n=83) | Change at Week 42 (n=33) | Change at Week 48 (n=77) | Change at Week 52 (n=35) | Change at Week 60 (n=40) | Change at Week 72 (n=38) | Change at End of study (n=93) |
|---|
| TMC435 150mg 12Wks PR24/48 | 31.65 | 0.42 | 2.50 | 3.85 | 3.93 | 5.47 | 5.27 | 5.50 | 3.79 | 2.75 | 6.41 | 2.09 | 3.26 | 0.25 | 0.70 | 0.13 |
Mean Change From Baseline in CD4+ Cell Count
(NCT01479868)
Timeframe: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
| Intervention | cell counts per microliter (Mean) |
|---|
| Baseline (n=93) | Change at Week 2 (n=89) | Change at Week 4 (n=91) | Change at Week 8 (n=92) | Change at Week 12 (n=91) | Change at Week 16 (n=88) | Change at Week 20 (n=84) | Change at Week 24 (n=89) | Change at Week 28 (n=82) | Change at Week 36 (n=83) | Change at Week 42 (n=33) | Change at Week 48 (n=77) | Change at Week 52 (n=35) | Change at Week 60 (n=40) | Change at Week 72 (n=38) | Change at End of Study (n=93) |
|---|
| TMC435 150mg 12Wks PR24/48 | 640.3 | -95.0 | -171.5 | -244.2 | -271.7 | -275.5 | -283.5 | -288.8 | -252.3 | -198.7 | -336.8 | -166.6 | -202.7 | -90.6 | -62.9 | -51.1 |
Percentage of Participants With Viral Relapse
Participants were considered to have a viral relapse when, at actual end of treatment, HCV RNA levels were less than 25 IU per mL undetectable; and during the follow-up period, HCV RNA levels were more than or equal to 25 IU per mL. (NCT01479868)
Timeframe: Week 1 to 72
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 10.3 |
Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load
(NCT01479868)
Timeframe: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
| Intervention | copies per milliliter (Mean) |
|---|
| Baseline (n=93) | Change at Week 2 (n=91) | Change at Week 4 (n=93) | Change at Week 8 (n=92) | Change at Week 12 (n=90) | Change at Week 16 (n=88) | Change at Week 20 (n=86) | Change at Week 24 (n=88) | Change at Week 28 (n=82) | Change at Week 36 (n=85) | Change at Week 42 (n=35) | Change at Week 48 (n=79) | Change at Week 52 (n=36) | Change at Week 60 (n=40) | Change at Week 72 (n=38) | Change at End of study (n=93) |
|---|
| TMC435 150mg 12Wks PR24/48 | 1.3726 | -0.0724 | -0.0704 | -0.0442 | -0.0655 | -0.0829 | -0.0847 | -0.0689 | -0.0564 | 0.0004 | -0.0623 | -0.0041 | 0.0011 | -0.0184 | -0.0265 | 0.0099 |
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to Day 126 that were absent before treatment or that worsened relative to pre-treatment state. (NCT01479868)
Timeframe: Week 1 to Week 72
| Intervention | participants (Number) |
|---|
| TEAEs | TESAEs |
|---|
| TMC435 150mg 12Wks PR24/48 | 102 | 6 |
Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable
Percentage of participants with HCV RNA less than (<) 25 IU/mL undetectable (undet.) or detectable (det.)/undetectable at specific time points were observed. (NCT01479868)
Timeframe: Week 4, 12, 24, 36, and 48
| Intervention | percentage of participants (Number) |
|---|
| Week 4: < 25 IU/mL HCV-RNA undet. (n=105) | Week 4:< 25 IU/mL HCV-RNA det./undet. (n=105) | Week 12:< 25 IU/mL HCV-RNA undet. (n=97) | Week 12:< 25 IU/mL HCV-RNA det./undet. (n=97) | Week 24:< 25 IU/mL HCV-RNA undet. (n=90) | Week 24:< 25 IU/mL HCV-RNA det./undet. (n=90) | Week 48:< 25 IU/mL HCV-RNA undet. (n=20) | Week 48:< 25 IU/mL HCV-RNA det./undet. (n=20) |
|---|
| TMC435 150mg 12Wks PR24/48 | 65.7 | 88.6 | 94.8 | 97.9 | 90.0 | 93.3 | 100 | 100 |
Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24)
The SVR 24 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 24 weeks after end of treatment. (NCT01479868)
Timeframe: 24 weeks after end of treatment (Week 24 or 48)
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 72.6 |
Percentage of Participants With Viral Breakthrough
Confirmed increase of more than 1 log10 IU per mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of more than 100 IU per mL in participants whose HCV RNA levels had previously been below the limit of quantification (less than 25 IU per mL detectable) or undetectable (less than 25 IU per mL undetectable), while on study therapy. (NCT01479868)
Timeframe: Week 1 to 48
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 11.4 |
Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure
Participants had confirmed HIV virologic failure if HIV viral load values were greater than or equal to 50 or 200 copies/mL among those who previously had less than 50 copies/mL. (NCT01479868)
Timeframe: Baseline to Week 72.
| Intervention | percentage of participants (Number) |
|---|
| Greater than or equal to 50 copies/mL | Greater than or equal to 200 copies/mL |
|---|
| TMC435 150mg 12Wks PR24/48 | 5.4 | 2.2 |
Percentage of Participants With Normalized Alanine Aminotransferase Levels
Participants with normalized alanine aminotransferase levels observed whose alanine aminotransferase levels were out of range at Baseline. (NCT01479868)
Timeframe: Baseline up to Week 72
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 81.5 |
Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12)
The SVR 12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 12 Weeks after end of treatment. (NCT01479868)
Timeframe: 12 weeks after end of treatment (Week 24 or 48)
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 73.6 |
Percentage of Participants With On-treatment Failure
Participants were considered as an on-treatment failure if, at actual end of treatment (EOT), there was confirmed detectable HCV RNA levels. (NCT01479868)
Timeframe: Week 1 to 48
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 17 |
CD4+ T-Cell Count (CD4) Change From Baseline
Change in CD4 T-cell count was calculated as value at the post entry visit minus the value at entry. (NCT01482767)
Timeframe: Entry and weeks (W) 8, 12, 24, 28, 40, 48, 52, 60, 72
| Intervention | cells/mm^3 (Median) |
|---|
| W8 CD4 change (A: n=115, B: n=101) | W12 CD4 change (A: n=106, B: n=95) | W24 CD4 change (A: n=61, B: n=52) | W28 CD4 change (A: n=53, B: n=44) | W40 CD4 change (A: n=50, B: n=37) | W48 CD4 change (A: n=22, B: n=35) | W52 CD4 change (A: n=23, B: n=0) | W60 CD4 change (A: n=39, B: n=36) | W72 CD4 change (A: n=33, B: n=27) |
|---|
| HCV Treatment-Experienced (Group B) | -170 | -202 | -263 | -284 | -276 | -237 | NA | -79 | -15 |
,| HCV Treatment-Naive (Group A) | -174 | -194 | -277 | -304 | -128 | -220 | -24 | -34 | 8 |
Number of Participants With Undetectable HCV RNA at Week 4, 8 and 12 Study Visits
Undetectable HCV RNA was defined as below the lower limit of quantitation of the assay and target not detected by Roche COBAS® TaqMan® HCV Test v2.0. (NCT01482767)
Timeframe: Weeks (W) 4, 8, 12
| Intervention | participants (Number) |
|---|
| W4 HCV RNA (A: n=122, B: n=116) | W8 HCV RNA (A: n=117, B: n=104) | W12 HCV RNA (A: n=109, B: n=99) |
|---|
| HCV Treatment-Experienced (Group B) | 3 | 28 | 43 |
,| HCV Treatment-Naive (Group A) | 9 | 48 | 68 |
Percentage of Participants With Sustained Virologic Response at 12 Weeks After Treatment Discontinuation (SVR12)
SVR12 was defined as undetectable HCV RNA (below the lower limit of quantitation of the assay and target not detected by Roche COBAS® TaqMan® HCV Test v2.0) at 12 weeks after treatment discontinuation. Participants without HCV RNA for SVR12 determination were considered not to have achieved SVR12. (NCT01482767)
Timeframe: 12 weeks after treatment discontinuation
| Intervention | percentage of participants (Number) |
|---|
| HCV Treatment-Naive (Group A) | 35.6 |
| HCV Treatment-Experienced (Group B) | 30.3 |
Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)
Number of participants who experienced an AE (sign or symptom or laboratory abnormality) of Grade 3 or higher at any time after baseline while on study. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening. (NCT01482767)
Timeframe: From study treatment dispensation to Week 72
| Intervention | percentage of participants (Number) |
|---|
| HCV Treatment-Naive (Group A) | 74.1 |
| HCV Treatment-Experienced (Group B) | 73.8 |
Percentage of Participants With HIV-1 Viral Load <50 Copies/mL
HIV-1 RNA testing was performed with Abbott RealTime HIV-1 assay (LLOQ=40 copies/mL) or with Roche COBAS AmpliPrep/Taqman HIV-1 assay (LLOQ=20 copies/mL). (NCT01482767)
Timeframe: Entry and weeks (W) 4, 8, 12, 24, 28, 40, 48, 52, 60, 72
| Intervention | percentage of participants (Number) |
|---|
| W0 HIV-1 RNA (A: n=133, B: n=122) | W4 HIV-1 RNA (A: n=123, B: n=114) | W8 HIV-1 RNA (A: n=117, B: n=104) | W12 HIV-1 RNA (A: n=108, B: n=99) | W24 HIV-1 RNA (A: n=62, B: n=52) | W28 HIV-1 RNA: (A: n=54, B: n=45) | W40 HIV-1 RNA (A: n=52, B: n=38) | W48 HIV-1 RNA (A: n=23, B: n=33) | W52 HIV-1 RNA (A: n=24, B: n=0) | W60 HIV-1 RNA (A: n=40, B: n=36) | W72 HIV-1 RNA (A: n=34, B: n=27) |
|---|
| HCV Treatment-Experienced (Group B) | 92.6 | 96.5 | 96.2 | 98.0 | 100.0 | 100.0 | 100.0 | 100.0 | NA | 97.2 | 100.0 |
,| HCV Treatment-Naive (Group A) | 100.0 | 98.4 | 100.0 | 98.1 | 100.0 | 98.1 | 92.3 | 100.0 | 100.0 | 100.0 | 97.1 |
Percentage of Participants With Sustained Virologic Response at 24 Weeks After Treatment Discontinuation (SVR24)
SVR24 was defined as undetectable HCV RNA (below the lower limit of quantitation of the assay and target not detected by Roche COBAS® TaqMan® HCV Test v2.0) at 24 weeks after treatment discontinuation. Participants without HCV RNA for SVR24 determination were considered not to have achieved SVR24. (NCT01482767)
Timeframe: 24 weeks after treatment discontinuation
| Intervention | percentage of participants (Number) |
|---|
| HCV Treatment-Naive (Group A) | 34.8 |
| HCV Treatment-Experienced (Group B) | 25.4 |
Number of Participants With Virologic Failure
Virologic failure is defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels more than 1,000 IU/mL at Weeks 4, 8, 12, 24, 32, or 40. (NCT01498068)
Timeframe: Week 4, Week 8, Week 12, Week 24, Week 32, or Week 40
| Intervention | Participants (Number) |
|---|
| Treatment-naïve | 1 |
| Treatment-experienced | 2 |
Number of Participants With Extended Rapid Virologic Response (eRVR)
A eRVR is defined as having hepatitis C virus (HCV) ribonucleic acid (RNA) less than 25 IU/mL, (target not detected) at Weeks 4 and 12 of treatment. (NCT01498068)
Timeframe: Week 4 and Week 12
| Intervention | Participants (Number) |
|---|
| Treatment-naïve | 13 |
| Treatment-experienced | 18 |
Number of Participants in Each Specific Category of Treatment Outcome
Participants were evaluated for following 4 categories of treatment outcome;Sustained Virologic Response 12 Weeks After Last Planned Dose of Study Medication(SVR12):hepatitis C virus (HCV)ribonucleic acid (RNA)<25 IU/mL(target not detected)12 weeks after last planned dose of study medication;Relapse:HCV RNA =>25 IU/mL during follow-up period after previous HCV RNA<25 IU/mL at planned end of treatment(EOT)[Week 24 or Week 48] and participant did not achieve SVR12planned;On treatment virologic failure:meeting virologic stopping rule and/or having detectable HCV RNA at EOT with viral breakthrough(having a confirmed increase >1 log 10 in HCV RNA level from the lowest level reached or confirmed value of HCV RNA >100 IU/mL in participants whose HCV RNA has previously become <25 IU/mL during treatment).Stopping rule defined as HCV RNA value >1000 IU/mL at Week 4, 8 or 12 or detectable HCV RNA at Week 24, 32 or 40;Other:HCV RNA <25 IU/mL at actual EOT and never HCV RNA =>25 IU/mL thereafter. (NCT01498068)
Timeframe: From Day 1 (Baseline) up to Follow-up visit (Week 36 or Week 60)
| Intervention | Participants (Number) |
|---|
| SVR12 | Relapse | On treatment virologic failure | Other |
|---|
| Treatment-experienced | 16 | 1 | 2 | 1 |
,| Treatment-naïve | 14 | 0 | 1 | 1 |
Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Less Than 25 IU/mL, (Target Not Detected) at Weeks 8, 12, 24, 32, 40 and 48
The table below shows number of participants with HCV RNA Less than 25 IU/mL, (target not detected) at Weeks 8, 12, 24, 32, 40 and 48. Only 3 treatment-naive and 14 Treatment-experienced participants were assigned to receive study treatment after Week 24. Only participants still receiving Treatment were assessed at 32, 40, and 48 weeks. (NCT01498068)
Timeframe: Weeks 8, 12, 24, 32, 40 and 48
| Intervention | Participants (Number) |
|---|
| Week 8 (n=16, 20) | Week 12 (n=16, 20) | Week 24 (n=16, 20) | Week 32 (n=3, 14) | Week 40 (n=3, 14) | Week 48 (n=3, 14) |
|---|
| Treatment-experienced | 19 | 19 | 18 | 12 | 12 | 12 |
,| Treatment-naïve | 16 | 15 | 15 | 2 | 2 | 1 |
Number of Participants With Rapid Virologic Response (RVR) at Week 4
A RVR is defined as having hepatitis C virus (HCV) ribonucleic acid (RNA) less than 25 IU/mL, (target not detected) at Week 4 (NCT01498068)
Timeframe: Week 4
| Intervention | Participants (Number) |
|---|
| Treatment-naïve | 14 |
| Treatment-experienced | 18 |
Percentage of Relapse-Free Subjects at Month 12 and Month 24
Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. (NCT01514370)
Timeframe: Month 12 and 24
| Intervention | Percentage of subjects (Number) |
|---|
| Month 12 | Month 24 |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 75.0 | 60.0 |
,| IFN Beta 1a 44 mcg TIW + Placebo | 67.5 | 50.0 |
Cumulative Number of New T1 (Hypointense) Lesions
Cumulative number of new T1 (Hypointense) lesions were reported. (NCT01514370)
Timeframe: Baseline up to Month 24
| Intervention | Lesions (Mean) |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 0.58 |
| IFN Beta 1a 44 mcg TIW + Placebo | 0.39 |
Number of Subjects With Clinical Significant Abnormality in Laboratory Parameters
Laboratory assessment included haematology, chemistry, and urinalysis. Clinical significance was determined by the investigator. (NCT01514370)
Timeframe: From screening up to Month 24
| Intervention | Subjects (Number) |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 9 |
| IFN Beta 1a 44 mcg TIW + Placebo | 4 |
Number of Subjects With One Concomitant Medication From Baseline up to Month 24
Number of subjects with at least one concomitant medication from baseline up to month 24 were reported. (NCT01514370)
Timeframe: Baseline up to Month 24
| Intervention | Subjects (Number) |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 28 |
| IFN Beta 1a 44 mcg TIW + Placebo | 20 |
Percentage of Subjects Treated With Glucocorticoids Due to Relapses During 24 Months
Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Percentage of subjects treated with glucocorticoids due to relapses during 24 Months were reported here. (NCT01514370)
Timeframe: Baseline up to Month 24
| Intervention | Percentage of Subjects (Number) |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 30.0 |
| IFN Beta 1a 44 mcg TIW + Placebo | 35.0 |
Percentage of Subjects With Active (New/Enlarging) T2 Lesions at Month 24
A single T2 lesion was defined as an area of increased signal on a given 3-millimeters axial image that was not referable to normally hyperintense structures. New T2 lesions were those that appear in areas where on the previous scan no abnormality was detected. All T2 lesions were detected by an MRI scan. (NCT01514370)
Timeframe: Month 24
| Intervention | Percentage of subjects (Number) |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 20.0 |
| IFN Beta 1a 44 mcg TIW + Placebo | 17.5 |
Time on Treatment (Adherence to Treatment)
Time up to which subjects were adhered to the treatment was reported. (NCT01514370)
Timeframe: Baseline up to 2.2 years
| Intervention | Years (Median) |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 1.93 |
| IFN Beta 1a 44 mcg TIW + Placebo | 1.92 |
Hazard Ratio for Time to First Documented Relapse
Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Hazard ratio for time to first documented relapse was planned to be reported as per SAP. (NCT01514370)
Timeframe: Baseline up to Date at which first Relapse Occurs assessed up to 24 months
| Intervention | Ratio (Number) |
|---|
| IFN Beta 1a 44 mcg TIW + [Curcumin (BCM95) and Placebo] | 0.808 |
Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation
AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 24 months. TEAEs include both Serious TEAEs and non-serious TEAEs. (NCT01514370)
Timeframe: Baseline up to Month 24
| Intervention | Subjects (Number) |
|---|
| Subjects with TEAE | Subjects with TE-SAE | Subjects with TEAEs leading to discontinuation | Subjects with TEAEs leading to death |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 16 | 1 | 1 | 0 |
,| IFN Beta 1a 44 mcg TIW + Placebo | 16 | 0 | 3 | 0 |
Percentage of Subjects Free From Expanded Disability Status Scale (EDSS) Progression at Month 12 and 24
Disability progression was assessed using EDSS. EDSS is based on a standardized neurological exam and focuses on symptoms that commonly occur in multiple sclerosis (MS) . Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). Disability progression was defined as an increase of EDSS score of at least 1.0 point compared to baseline for subjects with an EDSS =< 4.0. For subjects with an EDSS= 0 at baseline, EDSS progression was defined as an increase of EDSS score of at least 1.5 point. Percentage of subjects free from EDSS progression at Month 12 and 24 were reported (NCT01514370)
Timeframe: Month 12 and 24
| Intervention | Percentage of subjects (Number) |
|---|
| Month 12 | Month 24 |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 92.5 | 90.0 |
,| IFN Beta 1a 44 mcg TIW + Placebo | 82.5 | 85.0 |
Percentage of Subjects With Combined Unique Active (CUA) Lesions at Month 12 and 24
CUA lesion was defined as new gadolinium (Gd)-enhancing lesions on T1-weighted, or new or enlarging lesions on T2-weighted MRI scans, without double counting. (NCT01514370)
Timeframe: Month 12 and 24
| Intervention | Percentage of Subjects (Number) |
|---|
| Month 12 | Month 24 |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 7.5 | 15.0 |
,| IFN Beta 1a 44 mcg TIW + Placebo | 17.5 | 12.5 |
Annualized Relapse Rate at Month 12 and 24
Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Annualized relapse rate was calculated by dividing the total number of relapse events by the total number of days subjects participated in the study. This number was then multiplied by 365.25 to get an annualized rate. (NCT01514370)
Timeframe: Month 12 and 24
| Intervention | Relapse per year (Mean) |
|---|
| Month 12 | Month 24 |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 1.73 | 1.05 |
,| IFN Beta 1a 44 mcg TIW + Placebo | 1.40 | 1.14 |
Total Number of Reported Relapses at Month 3, 6, 12 and 24
Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. (NCT01514370)
Timeframe: Month 3, 6, 12 and 24
| Intervention | Relapses (Mean) |
|---|
| Month 3 | Month 6 | Month 12 | Month 24 |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 1.00 | 1.00 | 1.50 | 1.57 |
,| IFN Beta 1a 44 mcg TIW + Placebo | 1.00 | 1.00 | 1.00 | 1.75 |
Mean Number of New Gadolinium (Gd)-Enhancing Lesions at Month 12 and 24
New Gd-enhancing Lesions are a measure of inflammatory activity and were assessed using the Magnetic Resonance Imaging (MRI) scan. (NCT01514370)
Timeframe: Month 12 and 24
| Intervention | Lesions (Mean) |
|---|
| Month 12 | Month 24 |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 0.19 | 0.21 |
,| IFN Beta 1a 44 mcg TIW + Placebo | 0.46 | 0.13 |
Mean Number of New T1 (Hypointense) Lesions at Month 12 and 24
Mean number of new T1 (Hypointense) Lesions represents a measure of accumulation of inflammatory disease burden assessed on magnetic resonance imaging (MRI) scans. (NCT01514370)
Timeframe: Month 12 and 24
| Intervention | Lesions (Mean) |
|---|
| Month 12 | Month 24 |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 0.52 | 0.19 |
,| IFN Beta 1a 44 mcg TIW + Placebo | 0.48 | 0.04 |
Number of Subjects With Premature Termination From Treatment
Number of subjects with premature termination from treatment were reported. (NCT01514370)
Timeframe: Baseline up to Month 24
| Intervention | Subjects (Number) |
|---|
| Adverse event | Consent withdrawn | Lost to follow up | Protocol Violation | Unspecified |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 1 | 2 | 0 | 2 | 6 |
,| IFN Beta 1a 44 mcg TIW + Placebo | 3 | 1 | 2 | 3 | 7 |
Hazard Ratio for Time to First Sustained Expanded Disability Status Scale (EDSS) Progression
EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in MS. Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. EDSS values obtained during clinical attacks are not excluded for the assessment of EDSS progression. However, EDSS values obtained during MS attacks that are not confirmed after two consecutive assessments will be excluded from statistical analysis of confirmed EDSS progression. Hazard ratio for time to first sustained EDSS progression was planned to be reported as per SAP. (NCT01514370)
Timeframe: Baseline to date at which the first confirmed EDSS progression occurs, assessed up to 24 months
| Intervention | Ratio (Number) |
|---|
| IFN Beta 1a 44 mcg TIW + [Curcumin (BCM95) and Placebo] | 0.309 |
Number of Subjects With Active (New or Enlarging) T2 Lesions Assessed by Magnetic Resonance Imaging (MRI) at Month 12
A single T2 lesion was defined as an area of increased signal on a given 3-millimeters axial image that was not referable to normally hyperintense structures. New T2 lesions were those that appear in areas where on the previous scan no abnormality was detected. All T2 lesions were detected by an MRI scan. (NCT01514370)
Timeframe: Month 12
| Intervention | Participants (Count of Participants) |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 4 |
| IFN Beta 1a 44 mcg TIW + Placebo | 7 |
Flu-like Symptoms (FLS) Assessed by FLS Scale Score
Flu-like symptoms were measured using FLS score in which subjects were scored as per the presence and intensity of muscle aches, chills, and weakness, each separately, on a scale of 0-3 as follows: 0 = absent; 1 = mild, do not interfere with daily activities; 2 = moderate, sufficient to interfere with daily activities; and 3 = severe, bed rest require. Body temperature also was also recorded to determine the presence of fever using the following scale: 0 (≤ 37.2 °C); 1 (≥ 37.3 °C but < 37.8 °C); 2 (≥ 37.8 but < 38.4 °C); and 3 (≥ 38.4 °C).The scores for each symptom (muscle aches, chills, weakness, body temperature) was added together to provide the combined flu-like symptom score ranging from 0 to 12 where 0 indicates absence of any symptom and 12 indicates the worst severity of the symptoms. (NCT01514370)
Timeframe: Screening, Baseline, Month 3, 6, 12 and 24
| Intervention | Units on a scale (Mean) |
|---|
| Screening | Baseline | Month 3 | Month 6 | Month 12 | Month 24 |
|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | 2.39 | 2.22 | 1.91 | 1.96 | 1.45 | 1.68 |
,| IFN Beta 1a 44 mcg TIW + Placebo | 2.43 | 2.06 | 1.89 | 1.91 | 1.36 | 0.93 |
Change in Quantitative HBs Antigen at Week 12
Change in quantitative HBs antigen at week 12. The data were log transformed before analysis and the changes to baseline were analysed. Therefore, the reported values might be interpreted as percentage changes. Lower scores mean a better outcome. (NCT01524679)
Timeframe: week 12
| Intervention | IU/ml (Geometric Least Squares Mean) |
|---|
| Treatment Group | 0.7058 |
| Control Group | 0.9380 |
Change in Quantitative HBs Antigen at Week 24
Change in quantitative HBs antigen at week 24. The data were log transformed before analysis and the changes to baseline were analysed. Therefore, the reported values might be interpreted as percentage changes. Lower scores mean a better outcome. (NCT01524679)
Timeframe: week 24
| Intervention | IU/ml (Geometric Least Squares Mean) |
|---|
| Treatment Group | 0.3694 |
| Control Group | 0.7995 |
Cmax of Deleobuvir (BI 207127)
Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
| Intervention | nmol/L (Geometric Mean) |
|---|
| Day 9 (N=0, 17) | Day 17 (N=14, 19) | Day 66 (N=13, 15) |
|---|
| Group A | NA | 27000 | 10100 |
,| Group B | 10900 | 31400 | 16000 |
Cmax of Caffeine
Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Day 1 (N=16, 19) | Day 9 (N=15, 17) | Day 17 (N=14, 19) | Day 66 (N=13, 15) |
|---|
| Group A | 5170 | 4890 | 4830 | 5590 |
,| Group B | 5340 | 7220 | 6530 | 6450 |
Cmax of 1-OH-Midazolam (1-hydroxy-midazolam)
Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
| Intervention | nmol/L (Geometric Mean) |
|---|
| Day 1 (N=16, 19) | Day 9 (N=15, 17) | Day 17 (N=14, 19) | Day 66 (N=13, 15) |
|---|
| Group A | 5.57 | 6.50 | 6.46 | 5.05 |
,| Group B | 6.68 | 6.52 | 5.02 | 4.67 |
C6hr of Deleobuvir (BI 207127)
Concentration of an analyte in plasma at 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
| Intervention | nmol/L (Geometric Mean) |
|---|
| Day 9 (N=0, 17) | Day 17 (N=14, 19) | Day 66 (N=13, 14) |
|---|
| Group A | NA | 17900 | 5080 |
,| Group B | 5800 | 20800 | 10100 |
C24hr of Faldaprevir (BI 201335)
Concentration of an analyte in plasma at 24 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Day 9 (N=15,0) | Day 17 (N=14,19) | Day 66 (N=13,14) |
|---|
| Group A | 983 | 3670 | 1140 |
,| Group B | NA | 5410 | 2580 |
AUC 0-infinity of Tolbutamide
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
| Intervention | nmol*h/L (Geometric Mean) |
|---|
| Day 1 (N=16, 19) | Day 9 (N=13, 17) | Day 17 (N=14, 18) | Day 66 (N=12, 15) |
|---|
| Group A | 1940000 | 1800000 | 1520000 | 1330000 |
,| Group B | 2220000 | 1940000 | 1410000 | 1390000 |
AUC 0-infinity of Midazolam
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
| Intervention | nmol*h/L (Geometric Mean) |
|---|
| Day 1 (N=16, 19) | Day 9 (N=15, 17) | Day 17 (N=14, 19) | Day 66 (N=13, 15) |
|---|
| Group A | 79.7 | 117 | 127 | 75.5 |
,| Group B | 107 | 130 | 140 | 95.6 |
AUC 0-infinity of Caffeine
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Day 1 (N=16, 19) | Day 9 (N=15, 15) | Day 17 (N=14, 19) | Day 66 (N=13, 15) |
|---|
| Group A | 54900 | 42100 | 71900 | 120000 |
,| Group B | 77500 | 142000 | 170000 | 159000 |
AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
| Intervention | nmol*h/L (Geometric Mean) |
|---|
| Day 1 (N=16, 19) | Day 9 (N=15, 17) | Day 17 (N=14, 19) | Day 66 (N=13, 13) |
|---|
| Group A | 23.6 | 24.2 | 23.5 | 18.3 |
,| Group B | 26.0 | 28.5 | 22.8 | 20.8 |
AUC 0-6hr of Deleobuvir (BI 207127)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
| Intervention | nmol*h/L (Geometric Mean) |
|---|
| Day 9 (N=0, 17) | Day 17 (N=14, 19) | Day 66 (N=13, 15) |
|---|
| Group A | NA | 119000 | 36200 |
,| Group B | 41100 | 135000 | 59200 |
Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Day 9 (N=15,0) | Day 17 (N=14,19) | Day 66 (N=13,15) |
|---|
| Group A | 45600 | 138000 | 56200 |
,| Group B | NA | 173000 | 97300 |
Number of Participants With Sustained Virological Response (SVR12)
Sustained virologic response (SVR12): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level <25 IU/mL(international units per millilitre) undetectable at 12 weeks after the end of treatment. SVR12 was analyzed in a descriptive manner using frequency of participants who achieved SVR12. (NCT01525628)
Timeframe: 12 weeks post treatment
| Intervention | Participants (Number) |
|---|
| Group A | 13 |
| Group B | 13 |
| Group C | 11 |
| Group D | 10 |
| Group E | 3 |
Cmax of Faldaprevir (BI 201335)
Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Day 9 (N=15,0) | Day 17 (N=14,14) | Day 66 (N=13,15) |
|---|
| Group A | 3520 | 8780 | 4410 |
,| Group B | NA | 9950 | 6690 |
Cmax of Tolbutamide
Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
| Intervention | nmol/L (Geometric Mean) |
|---|
| Day 1 (N=16, 19) | Day 9 (N=15, 17) | Day 17 (N=14, 19) | Day 66 (N=13, 15) |
|---|
| Group A | 152000 | 146000 | 130000 | 110000 |
,| Group B | 170000 | 158000 | 126000 | 127000 |
Cmax of Midazolam
Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
| Intervention | nmol/L (Geometric Mean) |
|---|
| Day 1 (N=16, 19) | Day 9 (N=15, 17) | Day 17 (N=14, 19) | Day 66 (N=13, 15) |
|---|
| Group A | 21.1 | 29.9 | 31.9 | 21.3 |
,| Group B | 23.8 | 29.8 | 28.8 | 23.2 |
Change in Patient-reported Depression
The Beck Depression Inventory (BDI-I) scale was used to measure this outcome. The scale consists of 21 items to assess the intensity of depression in clinical and normal patients. Each item is a list of four statements arranged in increasing severity about a particular symptom of depression. Each item was scored from 0 - 3. If more than one score was provided for an item, the maximum score was considered the item score. The total score was calculated as the sum of all individual items and then compared to a key to determine the depression's severity. The standard key ranges were: 0 - 9 indicated minimal depression; 10 - 18 indicated mild depression; 19 - 29 indicated moderate depression and 30 - 63 indicated severe depression. Higher total scores indicate more severe depressive symptoms. (NCT01534182)
Timeframe: Baseline, 6 months
| Intervention | scores on a scale (Mean) |
|---|
| Fingolimod | -2.88 |
| Standard Disease Modifying Therapy (DMT) | -1.86 |
Change in Patient-reported Treatment Satisfaction
The Treatment Satisfaction Questionnaire for Medication (TSQM) contains 14 items assessing the following 4 domains: effectiveness (items 1 - 3), side effects (items 4 - 8), convenience (items 9 - 11) and global satisfaction (items 12 - 14). The primary outcome was measured on the global satisfaction domain. Item 12 scored as 1 (not at all confident) to 5 (extremely confident); item 13 scored as 1 (not at all certain) to 5 (extremely certain); and item 14 scored as 1 (extremely dissatisfied) to 7 (extremely satisfied). Responses to items were summed and transformed: specifically, TSQM v 1.4 domain scale scores were computed by adding the items loading on each domain. The lowest possible score was subtracted from the composite score and divided by the greatest possible score range. This provided a transformed score between 0 and 1 that was then multiplied by 100. The final transformed score ranges from 0 to 100, with higher scores indicating better treatment satisfaction. (NCT01534182)
Timeframe: Baseline, 6 months
| Intervention | scores on a scale (Mean) |
|---|
| Fingolimod | 22.69 |
| Standard Disease Modifying Therapy (DMT) | 13.92 |
Changes in Patient-reported Effectiveness, Side Effects and Convenience
TSQM v 1.4 domains for effectiveness, side effects and convenience were used to evaluate this outcome. The effectiveness domain for items 1 - 3 was scored as: 1 (extremely dissatisfied) to 7 (extremely satisfied). For the side effects domain, item 4 scored as 0(no) or 1(yes); item 5 scored as 1 (extremely bothersome) to 5 (not at all bothersome); and items 6 - 8 scored as 1 (a great deal) to 5 (not at all). For the convenience domain, items 9 and 10 scored as 1(extremely difficult) to 7 (extremely easy), and item 11 scored as 1 (extremely inconvenient) to 7 (extremely convenient). For each domain, scale scores were computed by adding the items loading on each domain. The lowest possible score was subtracted from the composite score and divided by the greatest possible score range. This provided a transformed score between 0 and 1 that was then multiplied by 100. The final transformed score ranges from 0 to 100, with higher scores indicating better treatment satisfaction. (NCT01534182)
Timeframe: Baseline, 6 months
| Intervention | scores on a scale (Mean) |
|---|
| Effectiveness | Side effects | Convenience |
|---|
| Fingolimod | 21.57 | 26.75 | 25.38 |
,| Standard Disease Modifying Therapy (DMT) | 11.56 | 13.07 | 10.57 |
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death
Participants were monitored for adverse events, serious adverse events and death throughout the study. (NCT01534182)
Timeframe: 6 months
| Intervention | Participants (Number) |
|---|
| Adverse events (serious and non-serious) | Serious adverse events | Deaths |
|---|
| Fingolimod | 73 | 2 | 0 |
,| Standard Disease Modifying Therapy (DMT) | 26 | 0 | 0 |
Percentage of Participants Who Had Undetectable HCV RNA at Week 4 Achieving SVR24
SVR24 rates were determined for only participants that had undetectable HCV RNA at Week 4 of treatment (Arm 1a and Arm 2a). HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL. (NCT01544920)
Timeframe: Up to Week 48
| Intervention | Percentage of participants (Number) |
|---|
| Arm 1a: Peg-IFN + RBV 24 Weeks | 87.0 |
| Arm 2a: BOC + Peg-IFN + RBV 24 Weeks | 97.2 |
Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) 24 Weeks After Completing Study Treatment (SVR24)
SVR24 rates were determined for all participants in Arm 1 and Arm 2. HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL. (NCT01544920)
Timeframe: Up to Week 74
| Intervention | Percentage of participants (Number) |
|---|
| Arm 1: Peg-IFN + RBV | 86.7 |
| Arm 2: BOC + Peg-IFN + RBV | 88.3 |
Overall Survival
The median time, in months, from randomization to OS event assessed using Kaplan-Meier estimates. One month=30.4 days (NCT01609010)
Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
| Intervention | months (Median) |
|---|
| Rituximab Monotherapy | NA |
| Rituximab + IFN | NA |
Overall Survival (OS) - Percentage of Participants With an Event
An overall survival event was defined as death due to any cause. (NCT01609010)
Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
| Intervention | percentage of participants (Number) |
|---|
| Rituximab Monotherapy | 13 |
| Rituximab + IFN | 11 |
Time to Disease Progression
The median time, in months, from randomization to disease progression event assessed using Kaplan-Meier estimates. One month=30.4 days (NCT01609010)
Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
| Intervention | months (Median) |
|---|
| Rituximab Monotherapy | 25.0 |
| Rituximab + IFN | 32.0 |
Treatment Failure - Percentage of Participants With an Event
Treatment failure was defined as an event of any of the following: progressive disease while receiving study treatment, death due to any cause, or the initiation of another type of treatment due to stable disease, progressive disease or relapse, or intolerance to study treatment. (NCT01609010)
Timeframe: Baseline (BL), Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
| Intervention | percentage of participants (Number) |
|---|
| Rituximab Monotherapy | 68 |
| Rituximab + IFN | 67 |
Treatment Failure - Time to Event
The median time, in months, between randomization and treatment failure event determined using Kaplan-Meier estimates. (NCT01609010)
Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
| Intervention | months (Median) |
|---|
| Rituximab Monotherapy | 21.5 |
| Rituximab + IFN | 28.0 |
Duration of Response
The median time, in months, from the date of the first observation of CR, CRu, or PR and the date of progressive disease (PD), censored observation, or death due to any cause. PD was defined as an increase of >50% compared to BL in the sum of the product of the two largest perpendicular parameters of measurable lymphoma, or the occurrence of new lesions. One month=30.4 days. Response duration was calculated amongst responders (CR+CRu+PR) with cutoffs for follow-up applied. (NCT01609010)
Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
| Intervention | months (Median) |
|---|
| CR+CRu+PR (n=102,113) | CR+CRu only (n=62,73) | CR only (n=50,62) |
|---|
| Rituximab + IFN | 30.0 | 44.4 | 50.7 |
,| Rituximab Monotherapy | 22.0 | NA | 59.5 |
Duration of Response - Percentage of Participants With an Event
Response duration was defined as the period between the date for first observation of CR, CRu or PR and the date of progressive disease (PD), censored observation or death of any cause. Response duration was also assessed for response defined as CR only. Response duration was calculated among responders (CR+CRu+PR) with cutoffs for follow-up applied. (NCT01609010)
Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
| Intervention | percentage of participants (Number) |
|---|
| CR, CRu, and PR (n=102,113) | CR and CRu only (n=62,73) | CR only (n=50,62) |
|---|
| Rituximab + IFN | 65 | 53 | 48 |
,| Rituximab Monotherapy | 63 | 44 | 38 |
Percentage of Participants Achieving CR or CRu
CR was defined as the complete disappearance of all previously detectable disease signs; the absence of palpable lymph nodes >1 cm or nodes >1.5 cm observed in CATscan; and negative bone marrow pathology, if initially positive. CRu was defined as CR, except that bone marrow results were indeterminate. (NCT01609010)
Timeframe: Weeks 10 and 16
| Intervention | percentage of participants (Number) |
|---|
| Week 10, Cycle 1 (n=156,157) | Week 16, Cycle 2 (n=123,124) |
|---|
| Rituximab + IFN | 9 | 41 |
,| Rituximab Monotherapy | 8 | 24 |
Percentage of Participants Achieving Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR)
CR was defined as the complete disappearance of all previously detectable disease signs; the absence of palpable lymph nodes greater than (>) 1 centimeter (cm) or nodes >1.5 cm observed in computerized axial tomography (CAT) scan; and negative bone marrow pathology, if initially positive. CRu was defined as CR, except that bone marrow results were indeterminate. PR was defined as a decrease of greater than or equal to (≥) 50 percent (%) compared with the BL value in the sum of the products of the two largest perpendicular diameters in all measurable and evaluable lesions; and a ≥50% reduction of the size from BL if hepato-splenomegaly was present. (NCT01609010)
Timeframe: Weeks 10 and 16
| Intervention | percentage of participants (Number) |
|---|
| Week 10, Cycle 1 (n=156,157) | Week 16, Cycle 2 (n=123,124) |
|---|
| Rituximab + IFN | 59 | 82 |
,| Rituximab Monotherapy | 54 | 74 |
Disease Progression - Percentage of Participants With an Event
A disease progression event was defined as tumor progression or death due to any cause (or a censored observation). (NCT01609010)
Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
| Intervention | percentage of participants (Number) |
|---|
| Rituximab Monotherapy | 60 |
| Rituximab + IFN | 62 |
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Treatment (SVR12)
SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than lower limit of quantitation [LLOQ] 12 weeks after the last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV). (NCT01609933)
Timeframe: 12 weeks after last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV); approximately 36 weeks after subject's initial dose of study drug in Substudy 1
| Intervention | percentage of participants (Number) |
|---|
| 2-DAA + PegIFN/RBV | 81.3 |
Percentage of Participants Achieving Virologic Response 24 Weeks Post Treatment (SVR24)
SVR24 was defined as HCV RNA level less than the LLOQ 24 weeks after the last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV). (NCT01609933)
Timeframe: 24 weeks after last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV); approximately 48 weeks after subject's initial dose of study drug in Substudy 1
| Intervention | percentage of participants (Number) |
|---|
| 2-DAA + PegIFN/RBV | 78.1 |
Percentage of Participants With Extended Rapid Virologic Response (eRVR)
eRVR was defined as HCV RNA level < LLOQ at Substudy 1 treatment weeks 4 through 12 without a confirmed HCV RNA >= LLOQ (NCT01609933)
Timeframe: Treatment weeks 4 through 12 of Substudy 1 (DAAs plus pegIFN alpha-2a and RBV)
| Intervention | percentage of participants (Number) |
|---|
| 2-DAA + PegIFN/RBV | 87.5 |
Number of Participants With Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after initiation of study drug through 30 days post-DAA dosing. For more details on AEs, see the AE section. (NCT01609933)
Timeframe: From first dose of study drug through 30 days after last dose of study drug (DAAs plus pegIFN alpha-2a and RBV) (up to 28 weeks).
| Intervention | participants (Number) |
|---|
| 2-DAA TEAE | 2-DAA TESAE |
|---|
| 2-DAA + PegIFN/RBV | 29 | 1 |
Change in Patient Visual Analog Scale Score for Pre-injection Anxiety
"The primary endpoint of the study was a change in patient self-reported 100 mm (10 cm) Visual Analogue Scale (VAS) score for pre-injection anxiety. VAS scale (min=0- max=100 mm (10cm)) 0= no anxiety; 100 mm (10 cm)=very severe anxiety.~Data from Weeks 2 and 3 were combined and averaged to obtain a single value as both weeks a 30 gauge needle was used for injection. The 30 gauge needle VAS mean refers to the mean for pre-injection anxiety for that needle size.~Data from Weeks 4 and 5 were combined and averaged to obtain a single value as both weeks a 25 gauge needle was used for injection. The 25 gauge needle VAS mean refers to the mean for pre-injection anxiety for that needle size." (NCT01641120)
Timeframe: Weeks 2, 3, 4, 5
| Intervention | cm (Mean) |
|---|
| 25 Gauge | 1.58 |
| 30 Gauge | 2.22 |
Fear of Injection
"Secondary endpoint was assessment of fear of injection based on patient questionnaires completed prior to each injection. The patient will respond to each statement on a scale which ranges from 1 (almost always) to 4 (almost never).~Data from Weeks 2 and 3 were combined and averaged to obtain a single value as both weeks a 30 gauge needle was used for injection. Mean describes fear of injection for the 30 gauge needle.~Data from Weeks 4 and 5 were combined and averaged to obtain a single value as both weeks a 25 gauge needle was used for injection. Mean describes fear of injection for the 25 gauge needle." (NCT01641120)
Timeframe: Weeks 2, 3, 4, 5
| Intervention | units on a scale (Mean) |
|---|
| 25 Gauge | 1.38 |
| 30 Gauge | 1.41 |
Perception of Needle
"Secondary endpoint was assessment of the perception of the needle based on patient questionnaires completed after each injection. The patient will respond to each statement on a scale which ranges from 1 (strongly agree) to 5 (strongly disagree).~A total of 6 statements were given to the participant the more strongly the participant agreed with the statement, the more favorably they perceived the needle.~Data from Weeks 2 and 3 were combined and averaged to obtain a single value as both weeks a 30 gauge needle was used for injection. Mean describes perception of the 30 gauge needle.~Data from Weeks 4 and 5 were combined and averaged to obtain a single value as both weeks a 25 gauge needle was used for injection. Mean describes perception of the 25 gauge needle." (NCT01641120)
Timeframe: Weeks 2, 3, 4, 5
| Intervention | units on a scale (Mean) |
|---|
| 25 Gauge | 2.58 |
| 30 Gauge | 1.94 |
Visual Analog Scale Score for Post-injection Pain
"The primary endpoint of the study was a change in patient self-reported 100 mm (10 cm) Visual Analogue Scale (VAS) score for post-injection pain.VAS scale (min=0 - max=100 mm (10 cm)) 0= no pain; 100 mm (10 cm)=very severe pain.~Data from Weeks 2 and 3 were combined and averaged to obtain a single value as both weeks a 30 gauge needle was used for injection. The 30 gauge needle VAS mean refers to the mean for post-injection pain for that needle size.~Data from Weeks 4 and 5 were combined and averaged to obtain a single value as both weeks a 25 gauge needle was used for injection. The 25 gauge needle VAS mean refers to the mean for post-injection pain for that needle size." (NCT01641120)
Timeframe: Weeks 2, 3, 4, 5
| Intervention | cm (Mean) |
|---|
| 25 Gauge | 1.201 |
| 30 Gauge | 0.764 |
Percentage of HBeAg(-) Participants Achieving Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels <2000 IU/mL at 24 Weeks Post-treatment
The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(-) participants. The percentage of HBeAg(-) participants with HBV DNA <2000 IU/mL at 24 weeks post-treatment was reported. (NCT01641926)
Timeframe: FU Week 24 (Study Week 72)
| Intervention | percentage of participants (Number) |
|---|
| HBeAg(-) PEG-Intron | 30.4 |
| HBeAg(-) PEGASYS | 33.3 |
Percentage of HBeAg(+) and HBeAg(-) Participants Achieving Alanine Aminotransferase (ALT) Normalization at 24 Weeks Post-treatment
ALT normalization is a desired goal of HBV treatment, which is defined as having abnormal ALT levels at baseline and subsequently normal ALT levels after receiving treatment, where normal is defined as ≤ 1x the upper limit of normal (ULN). The percentage of HBeAg(+) and HBeAg(-) participants achieving ALT normalization at 24 weeks post-treatment was reported. (NCT01641926)
Timeframe: FU Week 24 (Study Week 72)
| Intervention | percentage of participants (Number) |
|---|
| HBeAg(+) PEG-Intron | 49.3 |
| HBeAg(+) PEGASYS | 47.2 |
| HBeAg(-) PEG-Intron | 71.4 |
| HBeAg(-) PEGASYS | 61.4 |
Percentage of HBeAg(+) Participants Achieving HBeAg Seroconversion at 24 Weeks Post-treatment
Blood samples were drawn to assess the participant's seroconversion status at Follow-up (FU) Week 24. HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg. (NCT01641926)
Timeframe: FU Week 24 (Study Week 72)
| Intervention | percentage of participants (Number) |
|---|
| HBeAg(+) PEG-Intron | 25.4 |
| HBeAg(+) PEGASYS | 23.6 |
Percentage of HBeAg(+) Participants Achieving HBV DNA <2000 IU/mL at 24 Weeks Post-treatment
The Roche COBAS TaqMan HBV-(High Pure System Assay) was used to measure HBV DNA in blood samples of HBeAg(+)participants. The percentage of HBeAg(+) participants with HBV DNA <2000 IU/mL at 24 weeks post-treatment was reported. (NCT01641926)
Timeframe: FU Week 24 (Study Week 72)
| Intervention | percentage of participants (Number) |
|---|
| HBeAg(+) PEG-Intron | 23.9 |
| HBeAg(+) PEGASYS | 21.5 |
Percentage of HBeAg(+) Participants Achieving the Combined Response of HBeAg Seroconversion and HBV DNA <2000 IU/mL at 24 Weeks Post-treatment
HBeAg seroconversion was defined as loss of HBeAg in HBeAg(+) participants and development of antibody to HBeAg. HBV DNA levels in blood were measured by the Roche COBAS TaqMan HBV-(High Pure System Assay). The percentage of HBeAg(+) participants with the combined response of achieving both HBeAg conversion and HBV DNA levels <2000 IU/mL at 24 weeks post-treatment was reported. (NCT01641926)
Timeframe: FU Week 24 (Study Week 72)
| Intervention | percentage of participants (Number) |
|---|
| HBeAg(+) PEG-Intron | 14.8 |
| HBeAg(+) PEGASYS | 13.9 |
Mean Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 12
Blood samples were collected for the measurement of mean corpuscle volume at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the mean corpuscle volume values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12
| Intervention | Femtoliters (Mean) |
|---|
| Mean corpuscle volume; Week1; n=38, 39, 14, 12 | Mean corpuscle volume; Week2; n=41, 38, 14, 12 | Mean corpuscle volume; Week4; n=41, 38, 14, 13 | Mean corpuscle volume; Week6; n=41, 38, 12, 13 | Mean corpuscle volume; Week8; n=39, 39, 13, 13 | Mean corpuscle volume; Week12; n=38, 34, 12, 12 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -1.1 | -2 | 0.3 | 2.3 | 3.8 | 5.7 |
,| GSK2336805 60 mg, Genotype 1 HCV | -0.8 | -1.4 | 0.2 | 1.8 | 3 | 4.2 |
,| GSK2336805 60 mg, Genotype 4 HCV | -0.7 | -1.5 | -0.2 | 1.4 | 2.2 | 3.8 |
,| Telaprevir, Genotype 1 HCV | -0.4 | -1.4 | -0.8 | -0.2 | 3.1 | 5.3 |
Mean Change From Baseline in Red Blood Cell Count at the Indicated Time Points After Week 12
Blood samples were collected for the measurement of red blood cell count at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the red blood cell count values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4
| Intervention | Trillion cells per liter (Mean) |
|---|
| Red Blood Cell count; Week 18; n=38, 34, 13, 12 | Red Blood Cell count; Week 24; n=35, 33, 12, 11 | Red Blood Cell count; Week 30; n=13,10,2,2 | Red Blood Cell count; Week 36; n=12,7,1,2 | Red Blood Cell count; Week 42; n=10,6,2,2 | Red Blood Cell count; Week 48; n=9, 6,1,2 | Red Blood Cell count; PT Week 4; n=32,34,11,11 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -1.13 | -1.13 | -1.05 | -0.88 | -0.91 | -0.83 | -0.57 |
,| GSK2336805 60 mg, Genotype 1 HCV | -0.88 | -0.94 | -0.75 | -1.06 | -1.17 | -1.03 | -0.37 |
,| GSK2336805 60 mg, Genotype 4 HCV | -0.99 | -1.14 | -1.45 | -1.3 | -1.45 | -1.5 | -0.65 |
,| Telaprevir, Genotype 1 HCV | -1.19 | -1.19 | -1.45 | -1 | -0.55 | -0.4 | -0.66 |
Mean Change From Baseline in Red Blood Cell Count at the Indicated Time Points up to Week 12
Blood samples were collected for the measurement of red blood cell count at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the red blood cell count values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12
| Intervention | Trillion cells per liter (Mean) |
|---|
| Red Blood Cell count; Week1; n=38, 39, 14, 12 | Red Blood Cell count; Week2; n=41, 38, 14, 12 | Red Blood Cell count; Week4; n=41, 38, 14, 13 | Red Blood Cell count; Week6; n=41, 38, 12, 13 | Red Blood Cell count; Week8; n=39, 39, 13, 13 | Red Blood Cell count; Week12; n=38, 36, 12, 12 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -0.15 | -0.48 | -0.88 | -0.97 | -1.01 | -1.08 |
,| GSK2336805 60 mg, Genotype 1 HCV | -0.04 | -0.44 | -0.64 | -0.78 | -0.82 | -0.79 |
,| GSK2336805 60 mg, Genotype 4 HCV | -0.13 | -0.28 | -0.72 | -0.86 | -0.85 | -0.92 |
,| Telaprevir, Genotype 1 HCV | -0.18 | -0.57 | -1.03 | -1.28 | -1.45 | -1.61 |
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points up to Week 12
Blood pressure measurements were taken to observe vital signs and included SBP and DBP at the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and Post-treatment (PT) Follow Up (FU) Weeks 4, 12 and 24. Change from Baseline in SBP and DBP is summarized for each post-Baseline assessment up to Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) up to 12-week treatment period
| Intervention | Millimeters of mercury (mmHg) (Mean) |
|---|
| DBP; Day2; n=41, 40, 17, 13 | DBP; Week1; n=41, 39, 15, 13 | DBP; Week2; n=41, 39, 14, 13 | DBP; Week4; n=41, 39, 14, 13 | DBP; Week6; n=41, 39, 13, 13 | DBP; Week8; n=41, 39, 13, 13 | DBP; Week12; n=38, 35, 12, 13 | SBP; Day2; n=41, 40, 17, 13 | SBP; Week1; n=41, 39, 15, 13 | SBP; Week2; n=41, 39, 14, 13 | SBP; Week4; n=41, 39, 14, 13 | SBP; Week6; n=41, 39, 13, 13 | SBP; Week8; n=41, 39, 13, 13 | SBP; Week12; n=38, 35, 12, 13 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -1.2 | -0.4 | -0.4 | -1.2 | -1.2 | -2.1 | 0.3 | -1.4 | 0.9 | -2 | -3.6 | -0.4 | -3.7 | -1.9 |
,| GSK2336805 60 mg, Genotype 1 HCV | -1 | -2.2 | -1.7 | -4.4 | -4.8 | -2.9 | -4.4 | -0.8 | -3 | -0.7 | -4.2 | -3.8 | -1.5 | -1.4 |
,| GSK2336805 60 mg, Genotype 4 HCV | -1.5 | -1 | -2.8 | 0.8 | -1.6 | -2.4 | -1 | -1.3 | -2.6 | -4.2 | -5.2 | 0.2 | -4.2 | -2.6 |
,| Telaprevir, Genotype 1 HCV | -3 | 1 | -0.3 | -3.9 | -5.9 | -4.4 | -3.5 | -3.3 | -4.5 | -4.1 | -3.8 | -5.9 | -2.9 | -5.2 |
Mean Change From Baseline in Total Bilirubin and Creatinine at the Indicated Time Points After Week 12
Blood samples were collected for the measurement of total bilirubin and creatinine at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the direct bilirubin, total bilirubin and creatinine values are summarized for each post-Baseline assessment afterl Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4
| Intervention | Micromoles per liter (Mean) |
|---|
| Total bilirubin; Week 18; n=38, 34, 13, 12 | Total bilirubin; Week 24; n=35, 33, 12,11 | Total bilirubin; Week 30; n=13, 10, 3, 2 | Total bilirubin; Week 36; n=10, 7, 2, 2 | Total bilirubin; Week 42; n=9, 6, 1, 2 | Total bilirubin; Week 48; n=6, 6, 0, 2 | Total bilirubin PT Week 4; n=33, 34, 11,11 | Creatinine; Week 24; n=35, 33, 12, 11 | Creatinine; Week 18; n=38, 34, 13, 12 | Creatinine; Week 30; n=13, 10, 3, 2 | Creatinine; Week 36; n=10, 7, 2, 2 | Creatinine; Week 42; n=9, 6, 1, 2 | Creatinine; Week 48; n=6, 6, 0, 2 | Creatinine; PT Week 4; n=33, 34, 11,11 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 0.5 | -0.1 | -0.2 | 0 | 0.1 | -0.7 | -4.6 | -1.55 | -2.24 | 0.66 | 2.33 | 1.23 | -2.35 | 1.23 |
,| GSK2336805 60 mg, Genotype 1 HCV | 1.7 | 1 | 0.8 | 1.9 | 1.5 | 3.5 | -2.4 | -2.4 | -1.97 | 2.82 | 2.99 | 4.97 | 10.07 | -0.34 |
,| GSK2336805 60 mg, Genotype 4 HCV | 0.6 | 1.3 | -4 | -3 | -4 | -4 | -2.2 | 1.31 | 0.09 | -8.85 | -8 | -7.55 | -7.1 | -1.25 |
,| Telaprevir, Genotype 1 HCV | -1.4 | -1.3 | -2.3 | -3 | -14 | NA | -0.4 | -3.12 | -1.75 | -8.47 | -5.5 | -14.3 | NA | -1.7 |
Mean GSK2336805 Plasma Concentrations on Day 1, Day 2, Week 4, and Week 12
Plasma pharmacokinetic (PK) samples were collected for all participants on Day 1 (0 hour [h]-1h, 1h-4h, 4h-8h, 8h-20h), Day 2 (Predose [20-28h]), Week 4 (Predose [20-28h], 0h-1h, 1h-4h, 4h-8h, 8h-20h, 20h-28h) and Week 12 (Predose [20-28h]). PK Population is comprised of all participants who received GSK2336805 and underwent plasma PK sampling (intensive or sparse) during the study. (NCT01648140)
Timeframe: Day 1, Day 2, Week 4, and Week 12
| Intervention | nanograms per milliliter (ng/mL) (Mean) |
|---|
| Day 1 (0h-1h), n=1, 3 | Day 1 (1h-4h), n=35, 42 | Day 1 (4h-8h), n=0, 3 | Day 1 (8h-20h), n=0, 1 | Day 2 Predose (20-28h), n=36, 43 | Week 4 Predose (20-28h), n=33, 42 | Week 4 (0h-1h), n=2, 6 | Week 4 (1h-4h), n=46, 52 | Week 4 (4h-8h), n=22, 19 | Week 4 (8h-20h), n=1, 2 | Week 4 (20h-28h), n=11, 10 | Week 12 (Predose [20-28h]), n=26, 35 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | NA | 290.39 | NA | NA | 53.79 | 81.18 | 198.4 | 392.78 | 215.55 | NA | 51.24 | 45.99 |
,| GSK2336805 60 mg, Genotype 1 and Genotype 4 HCV | 604 | 445.18 | 221.33 | NA | 123.89 | 146.85 | 553 | 591.07 | 411.68 | 192.5 | 66.29 | 142.59 |
Number of Participants Achieving Very Rapid Virologic Response (vRVR), Rapid Virologic Response (RVR), Complete Early Virologic Response (cEVR), Sustained Virologic Response 12 and 24 (SVR12 and SVR24) With Response Guided Treatment (RGT)
Blood samples for the determination of HCV RNA levels were collected at Screening and Baseline, every study visit during the Treatment Period, and at PT FU Weeks 4, 12, and 24. vRVR is defined as plasma HCV RNA NCT01648140)
Timeframe: From the start of the treatment up to PT FU Week 24
| Intervention | Participants (Number) |
|---|
| vRVR | RVR | cEVR | SVR12 | SVR24 | SVR24 with RGT |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 8 | 23 | 33 | 30 | 27 | 17 |
,| GSK2336805 60 mg, Genotype 1 HCV | 12 | 23 | 30 | 26 | 25 | 17 |
,| GSK2336805 60 mg, Genotype 4 HCV | 6 | 9 | 13 | 0 | 0 | 0 |
,| Telaprevir, Genotype 1 HCV | 8 | 10 | 11 | 10 | 10 | 9 |
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) up to Week 12
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign(including an abnormal laboratory finding), symptom, or disease(new or exacerbated) temporally associated with the use of a medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect, important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. (NCT01648140)
Timeframe: From the start of study treatment up to Week 12
| Intervention | Participants (Number) |
|---|
| Any AE | Any SAE |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 39 | 0 |
,| GSK2336805 60 mg, Genotype 1 HCV | 37 | 2 |
,| GSK2336805 60 mg, Genotype 4 HCV | 13 | 1 |
,| Telaprevir, Genotype 1 HCV | 17 | 3 |
Number of Participants With Any AEs and Any SAEs After Week 12
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign(including an abnormal laboratory finding), symptom, or disease(new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect, important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. (NCT01648140)
Timeframe: From Week 12 up to PT Week 24 FU
| Intervention | Participants (Number) |
|---|
| Any AE | Any SAE |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 21 | 2 |
,| GSK2336805 60 mg, Genotype 1 HCV | 22 | 1 |
,| GSK2336805 60 mg, Genotype 4 HCV | 9 | 0 |
,| Telaprevir, Genotype 1 HCV | 8 | 0 |
Number of Participants With Shift From Baseline in Urinalysis Data up to Week 12
Urine samples were collected for urinalysis at Baseline, Weeks 2, 12, 18, 24, 48 and PT FU Weeks 4. Number of participants with shift from Baseline in urinalysis to normal (NL), abnormal (ANL) and missing (MIS) data up to Week 12 are summarized. Urine bilirubin (UBIL), urine glucose (UGLU), urine ketones (UKET), urine leukocyte esterase test (ULET) for detecting WBC, urine nitrite (UNIT), urine occult blood (UOB) were performed with dipstick method. Urine microscopy (UM) is performed to detect bacteria (BAC), red blood cells (RBC) and white blood cells (WBC). Other urinalysis parameter included urine pH (UpH) and urine specific gravity (USG). Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0), Weeks 2 and 12
| Intervention | Participants (Number) |
|---|
| Week 2, UBIL, BL MIS to PBL MIS, n=1,0,0,0 | Week 12, UBIL, BL MIS to PBL MIS,n=37,34,12,13 | Week 2, UGLU, BL MIS to PBL MIS, n=1,0,0,0 | Week 12, UGLU, BL MIS to PBL MIS,n=37,34,12,13 | Week 2, UKET, BL MIS to PBL MIS, n=1,0,0,0 | Week 12, UKET, BL MIS to PBL MIS,n=37,34,12,13 | Week 2, ULET, BL MIS to PBL MIS, n=1,0,0,0 | Week 12, ULET, BL MIS to PBL MIS,n=37,34,12,13 | Week 12, UMBT, BL MIS to PBL MIS,n=1,1,0,0 | Week 12, UMRBC, BL MIS to PBL MIS,n=4,5,2,2 | Week 12, UMWBC, BL MIS to PBL MIS, n=4,5,2,2 | Week 2, UNIT, BL MIS to PBL MIS, n=1,0,0,0 | Week 12, UNIT, BL MIS to PBL MIS,n=37,34,12,13 | Week 2, UOB, BL MIS to PBL MIS, n=1,0,0,0 | Week 12, UOB, BL MIS to PBL MIS,n=37,34,12,13 | Week 2, UPH, BL NL to PBL NL, n=1, 0,0,0 | Week 12, UPH, BL NL to PBL NL, n=37,34,12,13 | Week 12, UPH, BL NL to PBL ANL, n=37,34,12,13 | Week 2, USG, BL NL to PBL NL, n=1, 0,0,0 | Week 12, USG, BL NL to PBL NL, n=37,34,12,13 | Week 12, USG, BL NL to PBL ANL,n=37,34,12,13 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 1 | 37 | 1 | 37 | 1 | 37 | 1 | 37 | 1 | 4 | 4 | 1 | 37 | 1 | 37 | 1 | 36 | 1 | 1 | 37 | 0 |
,| GSK2336805 60 mg, Genotype 1 HCV | 0 | 34 | 0 | 34 | 0 | 34 | 0 | 34 | 1 | 5 | 5 | 0 | 34 | 0 | 34 | 0 | 34 | 0 | 0 | 34 | 0 |
,| GSK2336805 60 mg, Genotype 4 HCV | 0 | 13 | 0 | 13 | 0 | 13 | 0 | 13 | 0 | 2 | 2 | 0 | 13 | 0 | 13 | 0 | 13 | 0 | 0 | 12 | 1 |
,| Telaprevir, Genotype 1 HCV | 0 | 12 | 0 | 12 | 0 | 12 | 0 | 12 | 0 | 2 | 2 | 0 | 12 | 0 | 12 | 0 | 12 | 0 | 0 | 12 | 0 |
Mean Change From Baseline in ALP, ALT, AST, CK and GGT at the Indicated Time Points After Week 12
Blood samples were collected for the measurement of ALP, ALT, AST, CK and GGT at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the ALP, ALT, AST, CK and GGT values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4
| Intervention | International units per liter (Mean) |
|---|
| ALP; Week 18; n=38, 34, 13, 12 | ALP; Week 24; n=35, 33, 12, 11 | ALP; Week 30; n=13, 10, 3, 2 | ALP; Week 36; n=10, 7, 2, 2 | ALP; Week 42; n=9, 6, 1, 2 | ALP; Week 48; n=6, 6, 0, 2 | ALP; PT Week 4; n=33, 34, 11, 11 | ALT; Week 18; n=38, 34, 13, 12 | ALT; Week 24; n=35, 33, 12, 11 | ALT; Week 30; n=13, 10, 3, 2 | ALT; Week 36; n=10, 7, 2, 2 | ALT; Week 42; n=9, 6, 1, 2 | ALT; Week 48; n=6, 6, 0, 2 | ALT; PT Week 4; n=33, 34, 11, 11 | AST; Week 18; n=38, 34, 13, 12 | AST; Week 24; n=35, 33, 12, 11 | AST; Week 30; n=13, 10, 3, 2 | AST; Week 36; n=10, 7, 2, 2 | AST; Week 42; n=9, 6, 1, 2 | AST; Week 48; n=6, 6, 0, 2 | AST; PT Week 4; n=33, 34, 11, 11 | CK; Week 18; n=38, 34, 13, 12 | CK; Week 24; n=35, 33, 12, 11 | CK; Week 30; n=13, 10, 3, 2 | CK; Week 36; n=10, 7, 2, 2 | CK; Week 42; n=9, 6, 1, 2 | CK; Week 48; n=6, 6, 0, 2 | CK; PT Week 4; n=33, 34, 11, 11 | GGT; Week 18; n=38, 34, 13, 12 | GGT; Week 24; n=35, 33, 12, 11 | GGT; Week 30; n=13, 10, 3, 2 | GGT; Week 36; n=10, 7, 2, 2 | GGT; Week 42; n=9, 6, 1, 2 | GGT; Week 48; n=6, 6, 0, 2 | GGT; PT Week 4; n=33, 34, 11, 11 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 2.5 | 0.8 | 1.8 | 2 | 5.3 | 9.8 | -4.9 | -38.9 | -43.9 | -34.8 | -30.2 | -34.3 | -38.8 | -45.5 | -13.1 | -16.5 | -15.1 | -11.8 | -14.2 | -12.8 | -19.5 | -44 | -34.5 | -33 | -18.9 | -0.2 | 10.5 | -17.9 | -37.3 | -38.3 | -44.2 | -51.5 | -44.6 | -37.8 | -43.4 |
,| GSK2336805 60 mg, Genotype 1 HCV | 1.1 | 3.3 | -6.4 | 2.7 | 3.3 | 4.2 | -6.3 | -22.9 | -31.3 | -45.1 | -16.6 | -14.3 | -10.8 | -33.3 | -3.5 | -11.8 | -18.7 | -7.3 | -5.8 | -2.2 | -15.6 | -28.3 | -18.7 | -15.8 | -26.7 | -29.7 | 22.3 | -26.4 | -12.3 | -12.5 | -32.8 | -19.7 | -19.7 | -16.8 | -17.7 |
,| GSK2336805 60 mg, Genotype 4 HCV | 6.4 | 4.5 | 22.5 | 18 | 17.5 | 30 | -3.9 | -38.4 | -41.7 | -26 | -20.5 | -28 | -26.5 | -43.9 | -16.3 | -15.7 | -6.5 | -2.5 | -9 | -6.5 | -16 | -60.7 | 60.1 | -78.5 | -69 | -81 | -82.5 | 258.7 | -34.2 | -35.7 | -12 | -10 | -9 | -9.5 | -41.4 |
,| Telaprevir, Genotype 1 HCV | 2.2 | 2.1 | -8 | 2.5 | -2 | NA | -7 | -38.6 | -39.7 | -57.7 | -69 | -122 | NA | -31.5 | -18.8 | -23.8 | -27.7 | -27.5 | -54 | NA | -17.7 | -38.7 | -39 | -30 | -37.5 | -32 | NA | -21.7 | -30.2 | -37.4 | -38.7 | -40.5 | -17 | NA | -30.7 |
Mean Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count at the Indicated Time Points up to Week 12
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the basophils, eosinophils, lymphocytes, total neutrophils, platelet count and white blood cell count values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12
| Intervention | Giga cells per liter (Mean) |
|---|
| Basophils; Week1; n=38, 38, 14, 11 | Basophils; Week2; n=40, 38, 14, 10 | Basophils; Week4; n=41, 38, 14, 13 | Basophils; Week6; n=41, 37, 12, 12 | Basophils; Week8; n=38, 39, 13, 13 | Basophils; Week12; n=37, 36, 12, 12 | Eosinophils; Week1; n=38, 38, 14, 11 | Eosinophils; Week2; n=40, 38, 14, 10 | Eosinophils; Week4; n=41, 38, 14, 13 | Eosinophils; Week6; n=41, 37, 12, 12 | Eosinophils; Week8; n=38, 39, 13, 13 | Eosinophils; Week12; n=37, 36, 12, 12 | Lymphocytes; Week1; n=38, 38, 14, 11 | Lymphocytes; Week2; n=40, 38, 14, 10 | Lymphocytes; Week4; n=41, 38, 14, 13 | Lymphocytes; Week6; n=41, 37, 12, 12 | Lymphocytes; Week8; n=38, 39, 13, 13 | Lymphocytes; Week12; n=37, 36, 12, 12 | Monocytes; Week1; n=38, 38, 14, 11 | Monocytes; Week2; n=40, 38, 14, 10 | Monocytes; Week4; n=41, 38, 14, 13 | Monocytes; Week6; n=41, 37, 12, 12 | Monocytes; Week8; n=38, 39, 13, 13 | Monocytes; Week12; n=37, 36, 12, 12 | Total Neutrophils; Week1; n=38, 38, 14, 11 | Total Neutrophils; Week 2; n=40, 38, 14, 10 | Total Neutrophils; Week4; n=41, 38, 14, 13 | Total Neutrophils; Week6; n=41, 37, 12, 12 | Total Neutrophils; Week8; n=38, 39, 13, 13 | Total Neutrophils; Week12; n=37, 36, 12, 12 | Platelet Count; Week1; n=38, 39, 14, 11 | Platelet Count; Week2; n=41, 38, 14, 11 | Platelet Count; Week4; n=41, 38, 14, 13 | Platelet Count; Week6; n=41, 38, 12, 13 | Platelet Count; Week8; n=39, 39, 13, 13 | Platelet Count; Week12; n=38, 34, 12, 12 | White Blood Cell count; Week1; n=38, 38, 14, 11 | White Blood Cell count; Week2; n=40, 38, 14, 10 | White Blood Cell count; Week4; n=41, 38, 14, 13 | White Blood Cell count; Week6; n=41, 37, 12, 12 | White Blood Cell count; Week8; n=38, 39, 13, 13 | White Blood Cell count; Week12; n=37, 36, 12, 12 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -0.011 | -0.014 | -0.017 | -0.015 | -0.019 | -0.018 | -0.051 | -0.08 | -0.105 | -0.117 | -0.121 | -0.118 | -0.319 | -0.448 | -0.787 | -0.963 | -0.953 | -1.118 | -0.103 | -0.122 | -0.151 | -0.182 | -0.229 | -0.185 | -2.338 | -2.114 | -2.487 | -2.51 | -2.706 | -2.894 | -58.5 | -58 | -54.4 | -66.8 | -74.9 | -73.4 | -2.83 | -2.77 | -3.55 | -3.78 | -4.03 | -4.33 |
,| GSK2336805 60 mg, Genotype 1 HCV | -0.011 | -0.01 | -0.012 | -0.013 | -0.016 | -0.013 | -0.075 | -0.111 | -0.132 | -0.134 | -0.134 | -0.112 | -0.282 | -0.603 | -0.854 | -1.043 | -1.061 | -1.074 | -0.056 | -0.061 | -0.129 | -0.171 | -0.165 | -0.183 | -1.871 | -2.121 | -2.333 | -2.247 | -2.168 | -2.188 | -51.4 | -57.8 | -55.9 | -71.9 | -75.7 | -85.3 | -2.3 | -2.92 | -3.47 | -3.62 | -3.55 | -3.58 |
,| GSK2336805 60 mg, Genotype 4 HCV | -0.013 | -0.009 | -0.015 | -0.013 | -0.012 | -0.012 | -0.085 | -0.114 | -0.108 | -0.109 | -0.104 | -0.102 | -0.371 | -0.553 | -0.773 | -0.93 | -0.964 | -1.048 | -0.025 | -0.034 | -0.055 | -0.135 | -0.124 | -0.133 | -1.378 | -1.468 | -1.603 | -1.683 | -1.613 | -1.483 | -33.1 | -34.4 | -33.8 | -46 | -52.6 | -53 | -1.87 | -2.17 | -2.55 | -2.85 | -2.8 | -2.77 |
,| Telaprevir, Genotype 1 HCV | -0.012 | -0.009 | -0.01 | -0.013 | -0.009 | -0.011 | -0.059 | -0.059 | -0.079 | -0.113 | -0.13 | -0.106 | -0.608 | -0.675 | -0.989 | -1.334 | -1.256 | -1.438 | 0.034 | -0.091 | -0.126 | -0.245 | -0.185 | -0.219 | -1.158 | -1.186 | -1.412 | -1.413 | -1.222 | -1.649 | -59.5 | -41.4 | -56.2 | -71.3 | -60.1 | -58.8 | -1.81 | -2.01 | -2.61 | -3.09 | -2.8 | -3.42 |
Mean Change From Baseline in Chloride, Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 12
Blood samples were collected for the measurement of Chloride, bicarbonate, glucose, potassium, sodium, inorganic phosphorus and urea/BUN at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the chloride, bicarbonate, glucose, potassium, sodium, inorganic phosphorus and urea/BUN values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12
| Intervention | Millimoles per liter (Mean) |
|---|
| Chloride; Week1; n=40, 39, 15, 13 | Chloride; Week2; n=41, 38, 14, 13 | Chloride; Week4; n=41, 39, 14, 13 | Chloride; Week6; n=41, 38, 13, 13 | Chloride; Week8; n=40, 39, 13, 13 | Chloride; Week12; n=37, 35, 12, 13 | Bicarbonate; Week1; n=40, 39, 15, 13 | Bicarbonate; Week2; n=41, 38, 14, 13 | Bicarbonate; Week4; n=41, 39, 14, 13 | Bicarbonate; Week6; n=41, 38, 13, 13 | Bicarbonate; Week8; n=40, 39, 13, 13 | Bicarbonate; Week12; n=37, 35, 12, 13 | Glucose; Week1; n=40, 39, 15, 13 | Glucose; Week2; n=41, 38, 14, 13 | Glucose; Week4; n=41, 39, 14, 13 | Glucose; Week6; n=41, 38, 13, 13 | Glucose; Week8; n=40, 39, 13, 13 | Glucose; Week12; n=38, 35, 12, 13 | Potassium; Week1; n=40, 39, 15, 13 | Potassium; Week2; n=41, 38, 14, 13 | Potassium; Week4; n=41, 39, 14, 13 | Potassium; Week6; n=41, 38, 13, 13 | Potassium; Week8; n=40, 39, 13, 13 | Potassium; Week12; n=37, 35, 12, 13 | Sodium; Week1; n=40, 39, 15, 13 | Sodium; Week2; n=41, 38, 14, 13 | Sodium; Week4; n=41, 39, 14, 13 | Sodium; Week6; n=41, 38, 13, 13 | Sodium; Week8; n=40, 39, 13, 13 | Sodium; Week12; n=37, 35, 12, 13 | Inorganic Phosphorus; Week1; n=40, 39, 15, 13 | Inorganic Phosphorus; Week2; n=41,38,14,13 | Inorganic Phosphorus; Week4; n=41,39,14,13 | Inorganic Phosphorus; Week6; n=41,38,13,13 | Inorganic Phosphorus; Week8; n=40,39,13,13 | Inorganic Phosphorus; Week12; n=37,35,12,13 | Urea/BUN; Week1; n=40, 39, 15, 13 | Urea/BUN; Week2; n=41, 38, 14, 13 | Urea/BUN; Week4; n=41, 39, 14, 13 | Urea/BUN; Week6; n=41, 38, 13, 13 | Urea/BUN; Week8; n=40, 39, 13, 13 | Urea/BUN; Week12; n=37, 35, 12, 13 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 0.5 | 0.7 | 1.7 | 1.6 | 2 | 1.5 | 0 | -0.3 | -0.9 | -0.4 | -0.7 | -0.6 | -0.37 | -0.22 | -0.03 | -0.15 | -0.05 | -0.3 | -0.02 | -0.1 | -0.16 | -0.15 | -0.11 | -0.15 | -0.4 | -0.1 | 0.1 | 0.2 | 0.3 | 0.1 | -0.13 | -0.141 | -0.151 | -0.171 | -0.169 | -0.172 | 0.24 | 0.2 | 0.03 | -0.04 | -0.16 | -0.08 |
,| GSK2336805 60 mg, Genotype 1 HCV | -0.4 | 0.1 | 1 | 0.8 | 0.7 | 0.1 | -0.9 | -0.8 | -0.8 | -0.7 | -0.8 | -0.9 | -0.34 | -0.17 | 0.02 | -0.18 | -0.06 | -0.39 | -0.06 | -0.12 | -0.11 | -0.16 | -0.19 | -0.21 | -0.8 | -0.6 | -0.1 | -0.3 | -0.6 | -0.3 | -0.086 | -0.108 | -0.125 | -0.181 | -0.23 | -0.168 | 0.04 | -0.13 | -0.4 | -0.29 | -0.46 | -0.31 |
,| GSK2336805 60 mg, Genotype 4 HCV | -0.2 | -0.7 | 0.1 | -0.1 | -0.8 | 1.2 | -0.7 | -0.2 | -0.5 | 0.6 | 0 | -0.5 | 0.36 | 0.13 | -0.48 | -0.55 | -0.36 | -0.45 | -0.02 | -0.02 | -0.05 | -0.21 | -0.14 | -0.1 | -0.8 | -1.3 | -0.8 | 0 | -0.6 | 0.5 | -0.087 | -0.105 | -0.078 | -0.159 | -0.14 | -0.136 | -0.01 | -0.12 | -0.88 | -1.02 | -0.85 | -0.64 |
,| Telaprevir, Genotype 1 HCV | 0.6 | 0.5 | 1.6 | 0.8 | 2.2 | 1.9 | -1.2 | -1.5 | -1.4 | -1.5 | -1.2 | -1.1 | -0.03 | 0.11 | -0.11 | 0.18 | 0.04 | -0.23 | -0.11 | -0.39 | -0.34 | -0.45 | -0.51 | -0.38 | -0.2 | 0 | 0.4 | 0.2 | 1.1 | 0.8 | -0.122 | -0.081 | -0.077 | -0.121 | -0.112 | -0.117 | 0.19 | 0.08 | 0.11 | -0.39 | -0.07 | -0.11 |
Mean Change From Baseline in Chloride, Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus and Urea/BUN at the Indicated Time Points After Week 12
Blood samples were collected for the measurement of Chloride, bicarbonate, glucose, potassium, sodium, inorganic phosphorus and urea/bun at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the Chloride, Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus and Urea/Bun values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4
| Intervention | Millimoles per liter (Mean) |
|---|
| Chloride; Week 18; n=38, 34, 13, 12 | Chloride; Week 24; n=35, 33, 12, 11 | Chloride; Week 30; n=13, 10, 3, 2 | Chloride; Week 36; n=10, 7, 2, 2 | Chloride; Week 42; n=9, 6, 1, 2 | Chloride; Week 48; n=6, 6, 0, 2 | Chloride; PT Week 4; n=33, 34, 11, 11 | Bicarbonate; Week 18; n=38, 34, 13,12 | Bicarbonate; Week 24; n=35, 33, 12,11 | Bicarbonate; Week 30; n=13, 10, 3, 2 | Bicarbonate; Week 36; n=10, 7, 2, 2 | Bicarbonate; Week 42; n=9, 6, 1, 2 | Bicarbonate; Week 48; n=6, 6, 0, 2 | Bicarbonate; PT Week 4; n=33, 34, 11,11 | Glucose; Week 18; n=38, 34, 13, 12 | Glucose; Week 24; n=35, 33, 12, 11 | Glucose; Week 30; n=13, 10, 3, 2 | Glucose; Week 36; n=10, 7, 2, 2 | Glucose; Week 42; n=9, 6, 1, 2 | Glucose; Week 48; n=6, 6, 0, 2 | Glucose; PT Week 4; n=33, 34, 11, 11 | Potassium; Week 18; n=38, 34, 13, 12 | Potassium; Week 24; n=35, 33, 12, 11 | Potassium; Week 30; n=13, 10, 3, 2 | Potassium; Week 36; n=10, 7, 2, 2 | Potassium; Week 42; n=9, 6, 1, 2 | Potassium; Week 48; n=6, 6, 0, 2 | Potassium; PT Week 4; n=33, 34, 11,11 | Sodium; Week 18; n=38, 34, 13, 12 | Sodium; Week 24; n=35, 33, 12, 11 | Sodium; Week 30; n=13, 10, 3, 2 | Sodium; Week 36; n=10, 7, 2, 2 | Sodium; Week 42; n=9, 6, 1, 2 | Sodium; Week 48; n=6, 6, 0, 2 | Sodium; PT Week 4; n=33, 34, 11, 11 | Inorganic phosphorus; Week 18; n=38,34,13,12 | Inorganic phosphorus; Week 24; n=35,33,12,11 | Inorganic phosphorus; Week 30; n=13,10,3,2 | Inorganic phosphorus; Week 36; n=10,7,2,2 | Inorganic phosphorus; Week 42; n=9,6,1,2 | Inorganic phosphorus; Week 48; n=6,6,0,2 | Inorganic phosphorus; PT Week 4;n=33,34,11,11 | Urea/BUN; Week 18; n=38, 34, 13, 12 | Urea/BUN; Week 24; n=35, 33, 12, 11 | Urea/BUN; Week 30; n=13, 10, 3, 2 | Urea/BUN; Week 36; n=10, 7, 2, 2 | Urea/BUN; Week 42; n=9, 6, 1, 2 | Urea/BUN; Week 48; n=6, 6, 0, 2 | Urea/BUN; PT Week 4; n=33, 34, 11,11 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 1.9 | 2 | 1.9 | 1.3 | 1.3 | 1.3 | 0.5 | -0.3 | -1 | 0.4 | -0.9 | -0.7 | -1 | -0.7 | -0.28 | -0.33 | 0.03 | -0.38 | -0.28 | 0.25 | 0.24 | -0.19 | -0.13 | -0.03 | 0.24 | -0.1 | 0.1 | -0.16 | 0.7 | 0.4 | 1.1 | 0.4 | 0.4 | -0.2 | -0.1 | -0.161 | -0.139 | -0.156 | -0.121 | -0.08 | -0.167 | -0.084 | -0.19 | -0.22 | 0.69 | 0.65 | 0.34 | 0.67 | 0.35 |
,| GSK2336805 60 mg, Genotype 1 HCV | 1 | 0.7 | 0.3 | -0.1 | 0 | -1 | 0.2 | -1 | -1.2 | -2.2 | 0.1 | -0.2 | -1.3 | -0.5 | -0.13 | 0.27 | -0.26 | -0.37 | -0.12 | -0.3 | 0.18 | -0.24 | -0.12 | -0.23 | -0.1 | -0.2 | -0.3 | -0.13 | 0.1 | -0.1 | -1.4 | -0.7 | -0.5 | -1.2 | 0.1 | -0.13 | -0.13 | -0.118 | -0.167 | -0.108 | -0.108 | -0.003 | -0.23 | -0.55 | -0.16 | 0.04 | 0.5 | 0.4 | -0.19 |
,| GSK2336805 60 mg, Genotype 4 HCV | 0.5 | -0.2 | 3 | 1 | 0.5 | 0 | -1.5 | 0 | -0.4 | -2 | -1.5 | -1 | -0.5 | 1 | -0.23 | -0.22 | 0.9 | -0.7 | -0.15 | 4.55 | -0.07 | -0.2 | -0.32 | -0.1 | 0.2 | 0.1 | 0.05 | -0.1 | 0.4 | 0.4 | 0 | -0.5 | -1.5 | -2.5 | -0.5 | -0.111 | -0.107 | -0.225 | -0.125 | -0.1 | -0.35 | -0.085 | -0.25 | 0.02 | -0.5 | -0.25 | -0.5 | -0.5 | -0.47 |
,| Telaprevir, Genotype 1 HCV | 1.8 | 2.9 | 5.3 | 4.5 | 10 | NA | 0.6 | -1.2 | -1.8 | -1.3 | -2.5 | -4 | NA | -0.9 | -0.06 | -0.23 | -0.13 | -0.1 | 0.4 | NA | -0.12 | -0.41 | -0.34 | -0.1 | 0.15 | -0.1 | NA | -0.25 | 0.7 | 1.5 | 1.3 | 2 | 3 | NA | 1.1 | -0.092 | -0.119 | -0.267 | -0.195 | -0.15 | NA | 0.009 | -0.49 | -0.43 | -0.5 | -0.15 | 0.5 | NA | -0.62 |
Mean Change From Baseline in Creatinine Clearance at the Indicated Time Points After Week 12
Blood samples were collected for the measurement of estimated creatinine clearance by Cockcroft-Gault formula at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the estimated creatinine clearance values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4
| Intervention | mL/min (Mean) |
|---|
| Creatinine clearance; Week 18; n=38, 34, 13, 12 | Creatinine clearance; Week 24; n=35, 33, 12, 11 | Creatinine clearance; Week 30; n=13,10,3,2 | Creatinine clearance; Week 36; n=10,7,2,2 | Creatinine clearance; Week 42; n=9, 6,1,2 | Creatinine clearance; Week 48; n=6, 6,0,2 | Creatinine clearance; PT Week 4; n=33,34,11,11 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -0.1 | -1.9 | -4.8 | -11 | -6.1 | 3.2 | -1.5 |
,| GSK2336805 60 mg, Genotype 1 HCV | -1.1 | -1 | -10.4 | -8.1 | -13.3 | -15.8 | -1.3 |
,| GSK2336805 60 mg, Genotype 4 HCV | -4.3 | -6.1 | 7 | 1.5 | -1.5 | -4 | -5.3 |
,| Telaprevir, Genotype 1 HCV | -2.5 | -4.1 | -3.7 | -1 | 9 | NA | -2.7 |
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin and Creatinine at the Indicated Time Points up to Week 12
Blood samples were collected for the measurement of direct bilirubin, total bilirubin and creatinine at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the direct bilirubin, total bilirubin and creatinine values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12
| Intervention | Micromoles per liter (Mean) |
|---|
| Total Bilirubin; Week1; n=40, 39, 15, 13 | Total Bilirubin; Week2; n=41, 38, 14, 13 | Total Bilirubin; Week4; n=41, 39, 14, 13 | Total Bilirubin; Week6; n=41, 38, 13, 13 | Total Bilirubin; Week8; n=40, 39, 13, 13 | Total Bilirubin; Week12; n=37, 35, 12, 13 | Direct Bilirubin; Week1; n=1, 1, 1, 1 | Direct Bilirubin; Week2; n=1, 1, 1, 1 | Direct Bilirubin; Week4; n=1, 1, 0, 0 | Direct Bilirubin; Week6; n=1, 1, 0, 0 | Creatinine; Week1; n=40, 39, 15, 13 | Creatinine; Week2; n=41, 38, 14, 13 | Creatinine; Week4; n=41, 39, 14, 13 | Creatinine; Week6; n=41, 38, 13, 13 | Creatinine; Week8; n=40, 39, 13, 13 | Creatinine; Week12; n=38, 35, 12, 13 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 6.9 | 5.8 | 2.2 | 1.5 | 1.4 | 0.4 | 0 | 0 | 0 | 0 | -1.41 | -2.47 | -3.4 | -2.15 | -1.88 | -1.49 |
,| GSK2336805 60 mg, Genotype 1 HCV | 6.7 | 5.5 | 2.9 | 2.7 | 2.3 | 1.4 | 2 | 0 | 2 | 0 | 0.23 | -2.78 | -1.33 | -0.34 | -0.51 | -1.99 |
,| GSK2336805 60 mg, Genotype 4 HCV | 4.2 | 6.5 | 2.5 | 2.1 | 1.8 | 1.2 | -1 | 1 | NA | NA | -3.85 | -1.17 | -3.57 | -2.05 | -0.08 | -2.41 |
,| Telaprevir, Genotype 1 HCV | 8.1 | 5.6 | 0.7 | -0.5 | -0.3 | -2.8 | -8 | -14 | NA | NA | 5.12 | 4.13 | 5.35 | 7.1 | 9.43 | 6.85 |
Mean Change From Baseline in Electrocardiographic (ECG) Heart Rate Values at the Indicated Time Points up to Week 12
The ECG parameter heart rate was measured at Baseline, Weeks 1 and 12. Change from Baseline in ECG heart rate is summarized for each post-Baseline assessment up to Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 1 and 12
| Intervention | Beats per minute (Mean) |
|---|
| Week 1, n=41, 40, 15, 12 | Week 12, n=38, 35, 12, 13 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 3.3 | 8.3 |
,| GSK2336805 60 mg, Genotype 1 HCV | 0.8 | 5.1 |
,| GSK2336805 60 mg, Genotype 4 HCV | 4.8 | 8.5 |
,| Telaprevir, Genotype 1 HCV | 4.1 | 9.3 |
Mean Change From Baseline in Heart Rate at the Indicated Time Points up to Week 12
Vital sign monitoring included heart rate, measured at the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4, 12 and 24. Change from Baseline in heart rate is summarized for each post-Baseline assessment upto Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Day 2, Weeks 1, 2, 4, 6, 8, and 12
| Intervention | Beats per minute (Mean) |
|---|
| Heart Rate; Day2; n=41, 40, 17, 13 | Heart Rate; Week1; n=41, 39, 15, 13 | Heart Rate; Week2; n=41, 39, 14, 13 | Heart Rate; Week4; n=41, 39, 14, 13 | Heart Rate; Week6; n=41, 39, 13, 13 | Heart Rate; Week8; n=41, 39, 13, 13 | Heart Rate; Week12; n=38, 35, 12, 13 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 6.5 | 1.5 | 3.8 | 6.8 | 8 | 4.7 | 7 |
,| GSK2336805 60 mg, Genotype 1 HCV | 5.4 | 3.1 | 4.2 | 4.2 | 5 | 6.8 | 5.3 |
,| GSK2336805 60 mg, Genotype 4 HCV | 3.8 | 7.7 | 7.8 | 5.5 | 10.2 | 12.8 | 8.4 |
,| Telaprevir, Genotype 1 HCV | 9.3 | 8.1 | 8.7 | 10.7 | 13.8 | 14.2 | 11 |
Mean Change From Baseline in Hematocrit at the Indicated Time Points After Week 12
Blood samples were collected for the measurement of hematocrit at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the hematocrit values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4
| Intervention | Ratio (Mean) |
|---|
| Hematocrit; Week 18; n=38, 34, 13, 12 | Hematocrit; Week 24; n=35, 33, 12, 11 | Hematocrit; Week 30; n=13, 10, 2, 2 | Hematocrit; Week 36; n=12, 7, 1, 2 | Hematocrit; Week 42; n=10, 6, 2, 2 | Hematocrit; Week 48; n=9, 6, 1, 2 | Hematocrit; PT Week 4; n=32, 34, 11,11 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -0.083 | -0.0782 | -0.0713 | -0.0567 | -0.0623 | -0.0624 | -0.0293 |
,| GSK2336805 60 mg, Genotype 1 HCV | -0.0622 | -0.0635 | -0.0397 | -0.069 | -0.0802 | -0.0753 | -0.0135 |
,| GSK2336805 60 mg, Genotype 4 HCV | -0.0699 | -0.0823 | -0.1125 | -0.0895 | -0.111 | -0.1095 | -0.0354 |
,| Telaprevir, Genotype 1 HCV | -0.0776 | -0.0808 | -0.0955 | -0.087 | -0.0535 | -0.047 | -0.0362 |
Mean Change From Baseline in Hematocrit at the Indicated Time Points up to Week 12
Blood samples were collected for the measurement of hematocrit at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the hematocrit values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12
| Intervention | Ratio (Mean) |
|---|
| Hematocrit; Week1; n=38, 39, 14, 12 | Hematocrit; Week2; n=41, 38, 14, 12 | Hematocrit; Week4; n=41, 38, 14, 13 | Hematocrit; Week6; n=41, 38, 12, 13 | Hematocrit; Week8; n=39, 39, 13, 13 | Hematocrit; Week12; n=38, 36, 12, 12 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -0.0196 | -0.0539 | -0.0848 | -0.0859 | -0.0838 | -0.0843 |
,| GSK2336805 60 mg, Genotype 1 HCV | -0.0069 | -0.0465 | -0.0621 | -0.0685 | -0.0663 | -0.0589 |
,| GSK2336805 60 mg, Genotype 4 HCV | -0.0166 | -0.0335 | -0.0668 | -0.074 | -0.07 | -0.0688 |
,| Telaprevir, Genotype 1 HCV | -0.0201 | -0.0609 | -0.0999 | -0.1203 | -0.1235 | -0.1318 |
Mean Change From Baseline in Hemoglobin at the Indicated Time Points After Week 12
Blood samples were collected for the measurement of hemoglobin at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the hemoglobin values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4
| Intervention | Grams per liter (Mean) |
|---|
| Hemoglobin; Week 18; n=38, 34, 13, 12 | Hemoglobin; Week 24; n=35, 33, 12,11 | Hemoglobin; Week 30; n=13, 10, 2, 2 | Hemoglobin; Week 36; n=12, 7, 1, 2 | Hemoglobin; Week 42; n=10, 6, 2, 2 | Hemoglobin; Week 48; n=9, 6, 1, 2 | Hemoglobin; PT Week 4; n=32, 34, 11,11 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -33.6 | -33.4 | -30.2 | -26.7 | -27.1 | -25.9 | -16.5 |
,| GSK2336805 60 mg, Genotype 1 HCV | -26.7 | -28 | -21 | -30 | -31.7 | -29.3 | -11.7 |
,| GSK2336805 60 mg, Genotype 4 HCV | -29 | -32.3 | -40 | -35 | -40 | -41 | -16.8 |
,| Telaprevir, Genotype 1 HCV | -35 | -35.6 | -40 | -37 | -25 | -18 | -21.4 |
Mean Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 12
Blood samples were collected for the measurement of hemoglobin at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the hemoglobin values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12
| Intervention | Grams per liter (Mean) |
|---|
| Hemoglobin; Week1; n=38, 39, 14, 12 | Hemoglobin; Week2; n=41, 38, 14, 12 | Hemoglobin; Week4; n=41, 38, 14, 13 | Hemoglobin; Week6; n=41, 38, 12, 13 | Hemoglobin; Week8; n=39, 39, 13, 13 | Hemoglobin; Week12; n=38, 36, 12, 12 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -5.2 | -16.7 | -28.6 | -30.1 | -30.5 | -33 |
,| GSK2336805 60 mg, Genotype 1 HCV | -2.3 | -14.9 | -22.1 | -24.7 | -25.5 | -24.1 |
,| GSK2336805 60 mg, Genotype 4 HCV | -5.3 | -9.9 | -22.5 | -25.2 | -25.2 | -27.6 |
,| Telaprevir, Genotype 1 HCV | -6.6 | -20.5 | -34.4 | -40.8 | -44.9 | -47.4 |
Mean Change From Baseline in Creatinine Clearance at the Indicated Time Points up to Week 12
Blood samples were collected for the measurement of Creatinine Clearance at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. It is estimated by Cockcroft-Gault Equation. Change from Baseline in the Creatinine Clearance values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12
| Intervention | Milliliter per minute (mL/min) (Mean) |
|---|
| Creatinine Clearance; Week1; n=40, 39, 15, 13 | Creatinine Clearance; Week2; n=41, 38,14,13 | Creatinine Clearance; Week4; n=41, 39,14,13 | Creatinine Clearance; Week6; n=41, 38,13,13 | Creatinine Clearance; Week8; n=40, 39,13,13 | Creatinine Clearance; Week12; n=38,35,12,13 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 1.5 | 3.3 | 5 | 2.7 | 1.9 | -0.2 |
,| GSK2336805 60 mg, Genotype 1 HCV | -2.1 | 4.7 | 1.9 | -0.7 | 3.4 | 2.2 |
,| GSK2336805 60 mg, Genotype 4 HCV | 5.7 | -1.8 | 4.5 | 1.5 | -3 | 1.2 |
,| Telaprevir, Genotype 1 HCV | -9.5 | -9 | -9.1 | -19.1 | -17.8 | -14.3 |
Mean Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points After Week 12
Blood samples were collected for the measurement of mean corpuscle volume at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the mean corpuscle volume values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4
| Intervention | Femtoliters (Mean) |
|---|
| Mean Corpuscle Volume ; Week 18;n=38,34,13,12 | Mean Corpuscle Volume ; Week 24;n=35,33,12,11 | Mean Corpuscle Volume ; Week 30; n=13,10,2,2 | Mean Corpuscle Volume ; Week 36; n=12,7,1,2 | Mean Corpuscle Volume ; Week 42;n=10,6,2,2 | Mean Corpuscle Volume ; Week 48;n=9,6,1,2 | Mean Corpuscle Volume; PT Week 4; n=32,34,11,11 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 7.5 | 8.5 | 7.8 | 8.1 | 6.9 | 5.2 | 6.1 |
,| GSK2336805 60 mg, Genotype 1 HCV | 6.2 | 7.5 | 9.5 | 11.4 | 10.7 | 9 | 5.1 |
,| GSK2336805 60 mg, Genotype 4 HCV | 5.3 | 5.8 | 3 | 5.5 | 4 | 5 | 5.3 |
,| Telaprevir, Genotype 1 HCV | 8.5 | 7.6 | 11.5 | 2 | 1 | -1 | 5.8 |
Mean Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count at the Indicated Time Points After Week 12
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count at the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT Week 4. Change from Baseline in the basophils, eosinophils, lymphocytes, total neutrophils platelet count and white blood cell count values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4
| Intervention | Giga cells per liter (Mean) |
|---|
| Basophils; Week18; n=37, 33, 13, 12 | Basophils; Week24; n=34, 32, 12, 11 | Basophils; Week30; n=13, 10, 2, 2 | Basophils; Week36; n=12, 7, 1, 2 | Basophils; Week42; n=10, 6, 2, 2 | Basophils; Week48; n=7, 6, 1, 2 | Basophils; PT Week4; n=32, 34, 11, 11 | Eosinophils; Week18; n=37, 33, 13, 12 | Eosinophils; Week24; n=34, 32, 12, 11 | Eosinophils; Week30; n=13, 10, 2, 2 | Eosinophils; Week36; n=12, 7, 1, 2 | Eosinophils; Week42; n=10, 6, 2, 2 | Eosinophils; Week48; n=8, 6, 1, 2 | Eosinophils; PT Week4; n=32, 34, 11,11 | Lymphocytes; Week18; n=37, 33, 13,12 | Lymphocytes; Week24; n=34, 32, 12,11 | Lymphocytes; Week30; n=13, 10, 2, 2 | Lymphocytes; Week36; n=12, 7, 1, 2 | Lymphocytes; Week42; n=10, 6, 2, 2 | Lymphocytes; Week48; n=7, 6, 1, 2 | Lymphocytes; PT Week4; n=32, 34, 11,11 | Monocytes; Week18; n=37, 33, 13, 12 | Monocytes; Week24; n=34, 32, 12, 11 | Monocytes; Week30; n=13, 10, 2, 2 | Monocytes; Week36; n=12, 7, 1, 2 | Monocytes; Week42; n=10, 6, 2, 2 | Monocytes; Week48; n=7, 6, 1, 2 | Monocytes; PT Week4; n=32, 34, 11,11 | Total Neutrophils; Week18; n=37, 33,13,12 | Total Neutrophils; Week24; n=34, 32,12,11 | Total Neutrophils; Week30; n=13, 10,2,2 | Total Neutrophils; Week36; n=12, 7, 1,2 | Total Neutrophils; Week42; n=10, 6, 2,2 | Total Neutrophils; Week48; n=7, 6, 1, 2 | Total Neutrophils; PT Week4; n=32, 34,11,11 | Platelet Count; Week18; n=38, 34, 13,12 | Platelet Count; Week24; n=35, 33, 12,11 | Platelet Count; Week30; n=13, 10, 1, 2 | Platelet Count; Week36; n=12, 7, 1, 2 | Platelet Count; Week42; n=10, 6, 2, 2 | Platelet Count; Week48; n=9, 6, 1, 2 | Platelet Count; PT Week4; n=32, 34,11,11 | White Blood Cell count; Week18; n=37,33,13,12 | White Blood Cell count ; Week24; n=34,32,12,11 | White Blood Cell count ; Week30; n=13,10,2,2 | White Blood Cell count ; Week36; n=12,7,1,2 | White Blood Cell count ; Week42; n=10,6,2,2 | White Blood Cell count; Week48; n=7,6,1,2 | White Blood Cell count; PT Week4;n=32,34,11,11 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -0.019 | -0.018 | -0.018 | -0.02 | -0.015 | -0.007 | -0.007 | -0.119 | -0.128 | -0.124 | -0.081 | -0.105 | -0.071 | -0.069 | -1.081 | -1.181 | -1.225 | -1.267 | -1.135 | -0.779 | -0.681 | -0.186 | -0.206 | -0.151 | -0.255 | -0.184 | -0.066 | -0.047 | -2.702 | -2.527 | -2.402 | -2.503 | -2.23 | -1.129 | -1.158 | -73.7 | -67.5 | -70 | -64.1 | -56.1 | -37.7 | -20.4 | -4.1 | -4.06 | -3.92 | -4.13 | -3.67 | -2.09 | -1.97 |
,| GSK2336805 60 mg, Genotype 1 HCV | -0.01 | -0.01 | -0.012 | -0.006 | -0.005 | -0.007 | -0.003 | -0.127 | -0.131 | -0.116 | -0.123 | -0.1 | -0.11 | -0.085 | -1.157 | -1.092 | -1.085 | -1.286 | -1.22 | -1.4 | -0.7 | -0.141 | -0.156 | -0.135 | -0.18 | -0.093 | -0.147 | -0.031 | -2.378 | -2.187 | -2.252 | -2.777 | -3.085 | -2.488 | -0.808 | -87.5 | -78.8 | -71.9 | -75.7 | -67.3 | -68.8 | -28.9 | -3.81 | -3.58 | -3.59 | -4.39 | -4.52 | -4.17 | -1.64 |
,| GSK2336805 60 mg, Genotype 4 HCV | -0.012 | -0.013 | -0.02 | -0.01 | -0.015 | 0.005 | -0.003 | -0.068 | -0.041 | -0.04 | -0.05 | -0.04 | -0.05 | -0.018 | -0.973 | -1.057 | -1.845 | -1.92 | -1.93 | -2.2 | -0.737 | -0.143 | -0.121 | -0.06 | 0.015 | -0.01 | -0.085 | -0.053 | -1.463 | -1.3 | -2.085 | -1.63 | -1.815 | -1.445 | -0.671 | -52.1 | -51.9 | -36.5 | -34 | -22 | -14 | -12.9 | -2.65 | -2.52 | -4.05 | -3.55 | -3.8 | -3.8 | -1.45 |
,| Telaprevir, Genotype 1 HCV | -0.014 | -0.013 | -0.02 | -0.02 | 0 | 0.02 | -0.001 | -0.087 | -0.118 | -0.13 | -0.06 | -0.02 | 0.13 | -0.07 | -0.999 | -1.405 | -1.905 | -1.97 | -1.125 | 0.09 | -0.756 | -0.088 | -0.151 | -0.4 | -0.2 | -0.025 | 0.02 | 0.032 | -1.652 | -1.308 | -2.24 | -1.61 | -0.565 | 0.02 | -0.744 | -55.7 | -60.3 | -112 | -115 | -112 | 33 | -12.4 | -2.84 | -3 | -4.7 | -3.9 | -1.75 | 0.2 | -1.54 |
Apparent Clearance (CL/F) at Week 4
Blood samples for PK analysis of GSK2336805 was obtained on Week 4+1 day at predose and at 1, 2, 4, 7 and 24 hours postdose. CL/F was calculated as dose divided by AUC(0-tau). (NCT01648140)
Timeframe: Week 4 (24 h post dose)
| Intervention | Liter per hour (L/hr) (Geometric Mean) |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 14.63 |
| GSK2336805 60 mg, Genotype 1 and Genotype 4 HCV | 12.13 |
Apparent Volume of Distribution (Vz/F) at Week 4
Blood samples for PK analysis of GSK2336805 was obtained on Week 4+1 day at predose and at 1, 2, 4, 7 and 24 hours postdose. Vz/F was calculated as dose divided by (AUC[0-tau] lambda z) where lambda z is the terminal phase rate constant. (NCT01648140)
Timeframe: Week 4 (24 h post dose)
| Intervention | Liter per hour (L/hr) (Geometric Mean) |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 172.81 |
| GSK2336805 60 mg, Genotype 1 and Genotype 4 HCV | 125.09 |
Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) at Week 4
Blood samples for PK analysis of GSK2336805 was obtained on Week 4+1 day at predose and at 1, 2, 4, 7 and 24 hours postdose. (NCT01648140)
Timeframe: Week 4 (24 h post dose)
| Intervention | hour*nanogram per milliliter(hr*ng/mL) (Geometric Mean) |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 2733.34 |
| GSK2336805 60 mg, Genotype 1 and Genotype 4 HCV | 4948.23 |
Number of Participants Achieving eRVR
eRVR is defined as plasma HCV ribonucleic acid (RNA) NCT01648140)
Timeframe: Week 4 and Week 12
| Intervention | Participants (Number) |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 23 |
| GSK2336805 60 mg, Genotype 1 HCV | 21 |
| Telaprevir, Genotype 1 HCV | 9 |
| GSK2336805 60 mg, Genotype 4 HCV | 9 |
Time of Maximal Plasma Concentration (Tmax) of GSK2336805 at Week 4
Blood samples for PK analysis of GSK2336805 was obtained on Week 4+1 day at predose and at 1, 2, 4, 7, 24 hours postdose. (NCT01648140)
Timeframe: Week 4 (24 h post dose)
| Intervention | hour (Median) |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 2 |
| GSK2336805 60 mg, Genotype 1 and Genotype 4 HCV | 2 |
Maximum Plasma Concentration (Cmax) and Concentration at the End of the Dosing Interval (Ctau) of GSK2336805 at Week 4
Blood samples for PK analysis of GSK2336805 was obtained on Week 4+1 day at predose and at 1, 2, 4, 7, 24 hours post-dose. (NCT01648140)
Timeframe: Week 4 (24 h post dose)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cmax, n=11, 10 | Ctau, n=11, 10 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 335.35 | 31.37 |
,| GSK2336805 60 mg, Genotype 1 and Genotype 4 HCV | 618.75 | 49.31 |
Mean Change From Baseline in Albumin at the Indicated Time Points After Week 12
Blood samples were collected for the measurement of albumin at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the albumin values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4
| Intervention | Grams per liter (Mean) |
|---|
| Albumin; Week 18; n=38, 34, 13, 12 | Albumin; Week 24; n=35, 33, 12, 11 | Albumin; Week 30; n=13, 10, 3, 2 | Albumin; Week 36; n=10, 7, 2, 2 | Albumin; Week 42; n=9, 6, 1, 2 | Albumin; Week 48; n=6, 6, 0, 2 | Albumin; PT Week 4; n=33, 34, 11, 11 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -2.3 | -2.1 | -1.8 | -1.7 | -1.3 | -1.3 | -0.7 |
,| GSK2336805 60 mg, Genotype 1 HCV | -1.4 | -1.6 | -0.7 | -1.1 | -1.3 | -0.3 | -0.2 |
,| GSK2336805 60 mg, Genotype 4 HCV | -1 | -1.1 | -4.5 | -2 | -3 | -4 | -0.7 |
,| Telaprevir, Genotype 1 HCV | -1.8 | -2.3 | -3 | 2 | -1 | NA | 0.5 |
Mean Change From Baseline in Albumin at the Indicated Time Points up to Week 12
Blood samples were collected for the measurement of albumin at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the albumin values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12
| Intervention | Grams per liter (Mean) |
|---|
| Albumin; Week1; n=40, 39, 15, 13 | Albumin; Week2; n=41, 38, 14, 13 | Albumin; Week4; n=41, 39, 14, 13 | Albumin; Week6; n=41, 38, 13, 13 | Albumin; Week8; n=40, 39, 13, 13 | Albumin; Week12; n=37, 35, 12, 13 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | -0.6 | -1.3 | -1.9 | -2.2 | -2.6 | -2.1 |
,| GSK2336805 60 mg, Genotype 1 HCV | -0.3 | -1.5 | -1.5 | -1.5 | -1.7 | -1.3 |
,| GSK2336805 60 mg, Genotype 4 HCV | -1 | -0.2 | -1.2 | -2.1 | -1.5 | -1.6 |
,| Telaprevir, Genotype 1 HCV | -1.1 | -2 | -3 | -3.5 | -3.7 | -3.3 |
Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase (CK) and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points up to Week 12
Blood samples were collected for the measurement of ALP, ALT, AST, CK and GGT at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4 Change from Baseline in the ALP, ALT, AST, CK and GGT values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. (NCT01648140)
Timeframe: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12
| Intervention | International units per liter (Mean) |
|---|
| ALP; Week1; n=40, 39, 15, 13 | ALP; Week2; n=41, 38, 14, 13 | ALP; Week4; n=41, 39, 14, 13 | ALP; Week6; n=41, 38, 13, 13 | ALP; Week8; n=40, 39, 13, 13 | ALP; Week12; n=37, 35, 12, 13 | ALT; Week1; n=40, 39, 15, 13 | ALT; Week2; n=41, 38, 14, 13 | ALT; Week4; n=41, 39, 14, 13 | ALT; Week6; n=41, 38, 13, 13 | ALT; Week8; n=40, 39, 13, 13 | ALT; Week12; n=37, 35, 12, 13 | AST; Week1; n=40, 39, 15, 13 | AST; Week2; n=41, 38, 14, 13 | AST; Week4; n=41, 39, 14, 13 | AST; Week6; n=41, 38, 13, 13 | AST; Week8; n=40, 39, 13, 13 | AST; Week12; n=37, 35, 12, 13 | CK; Week1; n=40, 39, 15, 13 | CK; Week2; n=41, 38, 14, 13 | CK; Week4; n=41, 39, 14, 13 | CK; Week6; n=41, 38, 13, 13 | CK; Week8; n=40, 39, 13, 13 | CK; Week12; n=37, 35, 12, 13 | GGT; Week1; n=40, 39, 15, 13 | GGT; Week2; n=41, 38, 14, 13 | GGT; Week4; n=41, 39, 14, 13 | GGT; Week6; n=41, 38, 13, 13 | GGT; Week8; n=40, 39, 13, 13 | GGT; Week12; n=37, 35, 12, 13 |
|---|
| GSK2336805 40 mg, Genotype 1 HCV | 0 | 4.6 | 8.6 | 9.1 | 6.9 | 6.7 | -26.8 | -28.2 | -32.5 | -36 | -36.8 | -38.9 | -12.3 | -10 | -12.8 | -13.8 | -13.1 | -14.4 | 18.2 | -0.7 | 4.5 | -26 | -21.3 | -36.3 | -3.7 | -11.7 | -24.5 | -28.1 | -32.1 | -29.7 |
,| GSK2336805 60 mg, Genotype 1 HCV | 1.5 | 3.8 | 7.1 | 7.2 | 6.5 | 6.4 | -24.4 | -24.9 | -25.3 | -30.3 | -25.4 | -23.5 | -15.2 | -11.6 | -10.6 | -13.8 | -7.6 | -6.5 | -10.9 | -22.6 | -32.1 | 56.1 | -33.2 | -33.9 | -2 | -17.1 | -25.5 | -30.5 | -27.2 | -20.7 |
,| GSK2336805 60 mg, Genotype 4 HCV | -0.2 | 3.8 | 7.2 | 6.6 | 5.6 | 7.3 | -25.6 | -26.8 | -33 | -38.4 | -39.5 | -36.8 | -13.9 | -10.2 | -15.8 | -19.5 | -18.6 | -17.3 | -43.5 | -28.5 | -47.7 | -64.5 | -66.8 | -48.5 | -6.4 | -7.2 | -16.2 | -23.8 | -28.5 | -30 |
,| Telaprevir, Genotype 1 HCV | 3.9 | 9.4 | 11.7 | 16.6 | 15.5 | 11.7 | -30.7 | -35.4 | -40.4 | -40.8 | -39.9 | -43.7 | -18.1 | -18.4 | -20.9 | -21.6 | -21.8 | -25.7 | -3.3 | -9.6 | -14.4 | -21.5 | -30.3 | -20.9 | -10.3 | -19.9 | -27.7 | -30.5 | -30.5 | -33.6 |
OR for Impact of Duration of Treatment After Achieving RVR on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of duration of treatment after achieving RVR (>18 weeks versus <=18 weeks) on SVR. RVR was defined as HCV RNA <=25 IU/mL at Week 4 using CAP/CTM test. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: Baseline up to 96 weeks (assessed at Baseline, Week 4, EOT, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
| Intervention | odds ratio (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 1.04 |
OR for Impact of Duration of Treatment After Achieving cEVR on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of duration of treatment after achieving cEVR (>11 weeks versus <=11 weeks) on SVR. cEVR was defined as HCV RNA <=25 IU/mL at Week 12, but not at Week 4 using CAP/CTM test. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: Baseline up to 96 weeks (assessed at Baseline, Weeks 4, 12, EOT, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
| Intervention | odds ratio (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 2.77 |
OR for Impact of Cumulative Doses of Pegylated Interferon Alfa-2a on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of cumulative doses of pegylated interferon alfa-2a on SVR. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks
| Intervention | odds ratio (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 0.99 |
OR for Impact of Body Weight on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of body weight on SVR. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
| Intervention | odds ratio (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 1.01 |
OR for Impact of Baseline Viral Load Count on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of baseline viral load count (>800000 IU/mL versus <=800000 IU/mL) on SVR. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
| Intervention | odds ratio (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 1.07 |
OR for Impact of Baseline Level of Fibrosis (kPa) on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of baseline level of fibrosis on SVR. Level of fibrosis was measured in terms of kilopascals (kPa) using elastography. kPa score was categorized in 4 groups: 0 to 6.0; 6.1 to 9.9; 10.0 to 14.5; and 14.6 and above. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
| Intervention | odds ratio (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 0.53 |
OR for Impact of Baseline Alanine Transaminase (ALT) Level on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of baseline ALT level (>40 international units per liter [IU/L] versus <=40 IU/L) on SVR. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
| Intervention | odds ratio (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 0.12 |
Odds Ratio (OR) for Impact of Age on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of age (greater than [>] 42 years versus <=42 years) on SVR. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
| Intervention | odds ratio (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 0.21 |
OR for Impact of Cumulative Doses of Ribavirin on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of cumulative doses of ribavirin on SVR. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks
| Intervention | odds ratio (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 0.99 |
PPV of Complete Early Viral Response (cEVR) on SVR
cEVR was defined as HCV RNA <=25 IU/mL at Week 12, but not at Week 4 using CAP/CTM test. The percentage of participants with probability that the participant who develops cEVR would achieve SVR was termed as PPV of cEVR on SVR. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks
| Intervention | percentage of participants (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 60.3 |
Positive Predictive Value (PPV) of Rapid Viral Response (RVR) on SVR
RVR was defined as HCV RNA less than or equal to (<=) 25 IU/mL at Week 4 using CAP/CTM test. The percentage of participants with probability that the participant who develops RVR would achieve SVR was termed as PPV of RVR on SVR. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks
| Intervention | percentage of participants (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 93.1 |
Percentage of Participants Achieving Sustained Virological Response (SVR)
SVR was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) level undetectable (less than [<] 15 international units per milliliter [IU/mL]) 24 weeks after completion of the actual treatment period (measured using the COBAS AmpliPrep [CAP]/ COBAS TaqMan [CTM] test). Percentage of participants achieving SVR was reported. (NCT01659567)
Timeframe: At 24 weeks after end of treatment (EOT) (up to 96 weeks), where EOT = up to 72 weeks
| Intervention | percentage of participants (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 79.1 |
OR for Impact of Overall Duration of Treatment on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of overall duration of treatment on SVR. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: Baseline up to 96 weeks (assessed at Baseline, EOT, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
| Intervention | odds ratio (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 1.05 |
OR for Impact of Gender on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of gender (male versus female) on SVR. SVR was defined as HCV RNA level undetectable (<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). (NCT01659567)
Timeframe: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
| Intervention | odds ratio (Number) |
|---|
| Pegylated Interferon Alfa-2a and Ribavirin | 0.48 |
Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96
Change is calculated by HBsAg titer at baseline - HBsAg titer at week of assessments. (NCT01706575)
Timeframe: Baseline, Week 24, 72 and 96
| Intervention | international units per millilitre (Mean) |
|---|
| Baseline (n= 56) | Change at Week 24 (n= 56) | Change at Week 72 (n= 55) | Change at Week 96 (n= 55) |
|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | 0 | -546.32 | -815.69 | -728.16 |
Efficacy: Percentage of Participants With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48
(NCT01706575)
Timeframe: Baseline, Week 48
| Intervention | percentage of participants (Number) |
|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | 13.95 |
Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48)
(NCT01706575)
Timeframe: Baseline up to Week 48
| Intervention | percent change (Mean) |
|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | 59.13 |
Safety: Percentage of Participants With Adverse Events (AE)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. (NCT01706575)
Timeframe: Baseline up to Week 48
| Intervention | percentage of participants (Number) |
|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | 92.75 |
Efficacy: Number of Participants With Serum HBsAg Loss at Week 12 That Persisted up to Week 96
HBsAg loss is defined as HBsAg less than or equal to (NCT01706575)
Timeframe: Week 12 up to Week 96
| Intervention | participants (Number) |
|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | 1 |
Efficacy: Percentage of Participants With Serum Hepatitis B Surface Antigen (HBsAg) Decrease >/= 50% From Baseline at End of the Combination Treatment (Week 48)
Participants who stopped pegylated interferon (PEG-IFN) treatment during the add-on phase due to serum HBsAg loss and HBsAg seroconversion were considered as responders. (NCT01706575)
Timeframe: Baseline and Week 48
| Intervention | percentage of participants (Number) |
|---|
| Pegylated Interferon (Peginterferon) Alfa-2a | 67.44 |
Overall Survival
Time from randomization to death (event), or censored at last date known alive. (NCT01708941)
Timeframe: Assessed every 3 months for two years, then every 6 months for 3 years, then every 12 months for up to 10 years
| Intervention | months (Median) |
|---|
| Higher Dose Ipilimumab (With or Without HDI) | 20.1 |
| Lower Dose Ipilimumab (With or Without HDI) | 23.5 |
Overall Survival (OS)
Time from randomization to death (event), or censored at last date known alive (NCT01708941)
Timeframe: Assessed every 3 months for two years, then every 6 months for 3 years, then every 12 months for up to 10 years
| Intervention | months (Median) |
|---|
| Ipilimumab + HDI | 20.1 |
| Ipilimumab Alone | 24.7 |
Progression-free Survival
Progression-free survival (PFS) was defined as time from randomization to any documented disease progression or death from any cause, whichever occurred first (event), or censored at last date known alive. (NCT01708941)
Timeframe: Assessed every 3 months for two years, then every 6 months for 3 years, then every 12 months for up to 10 years
| Intervention | months (Median) |
|---|
| Higher Dose Ipilimumab (With or Without HDI) | 6.5 |
| Lower Dose Ipilimumab (With or Without HDI) | 3.8 |
Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as time from randomization to any documented disease progression or death from any cause, whichever occurred first (event), or censored at last date known alive. (NCT01708941)
Timeframe: Assessed every 3 months for two years, then every 6 months for 3 years, then every 12 months for up to 10 years
| Intervention | months (Median) |
|---|
| Ipilimumab + HDI | 7.5 |
| Ipilimumab Alone | 4.4 |
Percentage of Participants Achieving Undetectable HCV RNA During Treatment by Time Point
HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment. The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as HCV RNA < 9.3 IU/mL. (NCT01710501)
Timeframe: From Treatment Week (TW) 2 through end of treatment (up to 24 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Week 2 (n=29, 25, 29) | Week 4 (n=28, 26, 29) | Week 12 (n=28, 26, 28) | End of All Therapy (n=26, 25, 26) |
|---|
| Grazoprevir 100 mg + PEG-IFN + RBV | 55.2 | 89.7 | 100.0 | 100.0 |
,| Grazoprevir 25 mg + PEG-IFN + RBV | 34.5 | 82.1 | 96.4 | 92.3 |
,| Grazoprevir 50 mg + PEG-IFN + RBV | 32.0 | 76.9 | 92.3 | 92.0 |
Percentage of Participants Achieving SVR4
HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR4 was defined as HCV RNA <25 IU/mL (either target detected, unquantifiable or target not detected) 4 weeks after the end of all study therapy. (NCT01710501)
Timeframe: 4 weeks after end of treatment (up to 28 weeks total)
| Intervention | percentage of participants (Number) |
|---|
| Grazoprevir 25 mg + PEG-IFN + RBV | 76.9 |
| Grazoprevir 50 mg + PEG-IFN + RBV | 88.0 |
| Grazoprevir 100 mg + PEG-IFN + RBV | 92.3 |
Number of Participants Developing Post-baseline Antiviral Resistance to Grazoprevir Among Participants Not Achieving SVR24 Response
Post-baseline resistance associated variants (RAV) analysis was conducted by comparing the amino acid sequences at virologic failure time points to those at baseline (BL): Day 1, pre-dose. A post-BL variant was defined as an amino acid substitution within HCV NS3/4A that was present after the first dose at virologic failure and follow-up visits but not at BL. Post-BL variant analysis was conducted for participants who did not achieve SVR24 who had sequence data available. (NCT01710501)
Timeframe: From Day 1 up to Follow-up Week 24 (up to 48 weeks total)
| Intervention | participants (Number) |
|---|
| Grazoprevir 25 mg + PEG-IFN + RBV | 9 |
| Grazoprevir 50 mg + PEG-IFN + RBV | 5 |
| Grazoprevir 100 mg + PEG-IFN + RBV | 3 |
Number of Participants Discontinued From Study Treatment Due to AEs During the Treatment Period and First 14 Follow-up Days
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol -specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. (NCT01710501)
Timeframe: Up to 24 weeks
| Intervention | participants (Number) |
|---|
| Grazoprevir 25 mg + PEG-IFN + RBV | 1 |
| Grazoprevir 50 mg + PEG-IFN + RBV | 1 |
| Grazoprevir 100 mg + PEG-IFN + RBV | 1 |
Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12)
Hepatitis C virus ribonucleic acid (HCV RNA) was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR12 was defined as HCV RNA <25 IU/mL (either target detected, unquantifiable or target not detected) 12 weeks after the end of all study therapy. (NCT01710501)
Timeframe: 12 weeks after end of treatment (up to 36 weeks total)
| Intervention | percentage of participants (Number) |
|---|
| Grazoprevir 25 mg + PEG-IFN + RBV | 54.2 |
| Grazoprevir 50 mg + PEG-IFN + RBV | 84.0 |
| Grazoprevir 100 mg + PEG-IFN + RBV | 88.5 |
Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment by Time Point
HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment. The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. (NCT01710501)
Timeframe: From TW 2 through end of treatment (up to 24 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Week 2 (n=29, 25, 29) | Week 4 (n=28, 26, 29) | Week 12 (n=28, 26, 28) | End of all Therapy (n=26, 25, 26) |
|---|
| Grazoprevir 100 mg + PEG-IFN + RBV | 96.6 | 100.0 | 100.0 | 100.0 |
,| Grazoprevir 25 mg + PEG-IFN + RBV | 86.2 | 96.4 | 96.4 | 92.3 |
,| Grazoprevir 50 mg + PEG-IFN + RBV | 88.0 | 100.0 | 100.0 | 100.0 |
Number of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol -specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. (NCT01710501)
Timeframe: 14 days following last dose of study drug (up to 26 weeks)
| Intervention | participants (Number) |
|---|
| Grazoprevir 25 mg + PEG-IFN + RBV | 28 |
| Grazoprevir 50 mg + PEG-IFN + RBV | 28 |
| Grazoprevir 100 mg + PEG-IFN + RBV | 28 |
Percentage of Subjects Achieving SVR24
HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR24 was defined as HCV RNA <25 IU/mL (either target detected, unquantifiable or target not detected) 24 weeks after the end of all study therapy. (NCT01710501)
Timeframe: 24 weeks after end of treatment (up to 48 weeks total)
| Intervention | percentage of participants (Number) |
|---|
| Grazoprevir 25 mg + PEG-IFN + RBV | 54.2 |
| Grazoprevir 50 mg + PEG-IFN + RBV | 84.0 |
| Grazoprevir 100 mg + PEG-IFN + RBV | 84.6 |
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death
AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug. (NCT01741545)
Timeframe: From Day 1 to end of follow-up (maximum of 60 weeks for Cohort A and 72 weeks for Cohort B)
| Intervention | Percentage of participants (Number) |
|---|
| AEs on treatment | SAEs | Death | AE leading to discontinuation | Dose reduction - Lambda | Dose reduction - RBV |
|---|
| Cohort A | 10 | 0 | 0 | 1 | 0 | 0 |
,| Cohort B | 38 | 4 | 0 | 3 | 1 | 2 |
Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment
Flu-like symptoms were defined as pyrexia or chills or pain. Musculoskeletal symptoms were defined as arthralgia or myalgia or back pain. (NCT01741545)
Timeframe: After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)
| Intervention | Percentage of participants (Number) |
|---|
| Flu-like symptoms | Musculoskeletal symptoms |
|---|
| Cohort A | 8.3 | 0 |
,| Cohort B | 12.8 | 15.4 |
Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-Up Week 12
SVR12 was defined as HCV ribonucleic acid (RNA) less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. (NCT01741545)
Timeframe: Follow-up Week 12
| Intervention | Percentage of participants (Number) |
|---|
| Cohort A | 91.7 |
| Cohort B | 89.7 |
Percentage of Participants With Complete Early Virologic Response (cEVR)
cEVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 12. (NCT01741545)
Timeframe: Treatment Week 12
| Intervention | Percentage of participants (Number) |
|---|
| Cohort A | 91.7 |
| Cohort B | 92.3 |
Percentage of Participants With End of the Treatment Response (EOTR)
EOTR was defined as HCV RNA less than the lower limit of quantitation, target not detected at end of treatment. (NCT01741545)
Timeframe: End of the treatment (Week 12 for Cohort A, Week 24 for Cohort B)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort A | 100 |
| Cohort B | 100 |
Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities
Laboratory abnormalities were determined and graded using the Division of acquired immunodeficiency syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, version 1.0. International Normalized Ratio (INR): >2.0*Upper limit of normal (ULN); Alanine aminotransferase (ALT) : >5*ULN; Aspartate aminotransferase (AST): >5*ULN; Prothrombin Time (PT): >1.50*ULN; Bilirubin (Total): >2.5*ULN; Triglycerides (fasting): >750 mg/dL. (NCT01741545)
Timeframe: After day 1 to to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)
| Intervention | Participants (Count of Participants) |
|---|
| INR | ALT | AST | PT | Bilirubin | Triglycerides |
|---|
| Cohort A | 0 | 2 | 0 | 0 | 2 | 0 |
,| Cohort B | 1 | 1 | 2 | 1 | 7 | 1 |
Percentage of Participants With Rapid Virologic Response (RVR)
RVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 4. (NCT01741545)
Timeframe: Treatment Week 4
| Intervention | Percentage of participants (Number) |
|---|
| Cohort A | 91.7 |
| Cohort B | 76.9 |
Percentage of Participants With Treatment-Emergent Cytopenic Abnormalities On-Treatment
Cytopenic abnormalities were defined as anemia: Hemoglobin (Hb) <10 g/dL, and/or neutropenia: absolute neutrophils and bands (ANC) <750 mm^3, and/or thrombocytopenia: platelets <50,000 mm^3. (NCT01741545)
Timeframe: After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort A | 0 |
| Cohort B | 0 |
Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24)
SVR24 was defined as HCV RNA less than the lower limit of quantitation, target detected or target not detected at follow-up week 24. (NCT01741545)
Timeframe: Follow-up Week 24
| Intervention | Percentage of participants (Number) |
|---|
| Cohort A | 66.7 |
| Cohort B | 30.8 |
Cmax of Interferon Beta-1a
Primary outcome measure for pharmacokinetics analysis Blood samples were taken before the injection, then after 15 min, 30 min, 45 min, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours and 48 hours. (NCT01766024)
Timeframe: 0 to 48 hours post-dose
| Intervention | pg/ml (Median) |
|---|
| BCD-033 | 104.9 |
| Rebif | 102.4 |
AUC(0-168) and AUC(0-∞) of Neopterin and MxA Protein
Primary outcome measure for pharmacodynamics analysis. Blood samples were taken before the injection, then after 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours. (NCT01766024)
Timeframe: 0 to 168 hours post-dose
| Intervention | (ng/ml)*h (Median) |
|---|
| neopterin | MxA protein |
|---|
| BCD-033 | 552.7 | 2444.2 |
,| Rebif | 537.6 | 2131.2 |
Area Under Concentration-time Curve (AUC) of Interferon (IFN) Beta-1a From the Moment of Drug Administration Until 48 Hours and to Infinity(AUC(0-48) and AUC(0-∞) Respectively)
Primary outcome measure for pharmacokinetics analysis. Blood samples were taken before the injection, then after 15 min, 30 min, 45 min, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours and 48 hours. (NCT01766024)
Timeframe: 0 to 48 hours post-dose
| Intervention | (pg/ml)•h (Median) |
|---|
| BCD-033 | 6318.3 |
| Rebif | 6807.9 |
Normalization of Alanine Transferase Test
Liver function test,showing resolution of the inflammation of liver parenchyma (NCT01770483)
Timeframe: 48week
| Intervention | participants (Number) |
|---|
| Control Group | 11 |
| Study Group | 11 |
Sustained Viral Response,
Sustained viral response ,is negative Hepatitis C Virus(PCR)RNA test six months after end of treatment. (NCT01770483)
Timeframe: 48 WEEK
| Intervention | participants (Number) |
|---|
| Control Group | 13 |
| Study Group | 11 |
Percentage of Participants With Virologic Failure During Treatment
Virologic failure during treatment was defined as HCV ribonucleic acid (RNA) confirmed greater than or equal to the lower limit of quantification (≥ LLOQ) after HCV RNA < LLOQ during treatment or confirmed HCV RNA ≥ LLOQ at the end of treatment. (NCT01854528)
Timeframe: Baseline to end of treatment (12 weeks for 3-DAA/RBV and 24 or 48 weeks for TPV/RBV)
| Intervention | percentage of participants (Number) |
|---|
| 3-DAA/RBV | 0 |
| TPV/RBV | 19.1 |
Percentage of Participants With Virologic Relapse After Treatment
Participants who completed treatment with plasma HCV RNA less than the lower limit of quantification (NCT01854528)
Timeframe: Between end of treatment (Week 12 for 3-DAA/RBV and Week 24 or 48 for TPV/RBV) and Post-treatment (up to Week 12 Post-treatment)
| Intervention | percentage of participants (Number) |
|---|
| 3-DAA/RBV | 0 |
| TPV/RBV | 6.3 |
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL. (NCT01854528)
Timeframe: 12 weeks after the last dose of study drug
| Intervention | percentage of participants (Number) |
|---|
| 3-DAA/RBV | 100.0 |
| TPV/RBV | 66.0 |
Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 24 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL. (NCT01854528)
Timeframe: 24 weeks after the last dose of study drug
| Intervention | percentage of participants (Number) |
|---|
| 3-DAA/RBV | 99.0 |
| TPV/RBV | 66.0 |
Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS)
SF-36V2 is a generic 36-item questionnaire measuring HRQoL covering 2 summary measures: PCS and MCS; it consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, bodily pain, and general health perception. Participants self-report on items in a subscale that have choices per item. Scoring is done for both PCS subscale scores and summary scores; for each, the range is 0 (worst HRQoL) to 100 (best HRQoL). (NCT01854697)
Timeframe: From Day 1 of treatment up to 12 weeks for Arms A, C and D and up to 24 or 48 weeks for Arms B and E
| Intervention | units on a scale (Mean) |
|---|
| Arm A: 3-DAA + RBV in GT1a | 0.5 |
| Arm B: TPV/PR in GT1a | -5.5 |
| Arm C: 3-DAA + RBV in GT1b | 0.4 |
| Arm D: 3-DAA in GT1b | 2.2 |
| Arm E: TPV/PR in GT1b | -5.5 |
Percentage of Participants With Virologic Failure During Treatment
"Participants in Arms A, C or D demonstrating any of the following were considered virologic failures and discontinued therapy:~Confirmed increase from nadir in HCV RNA (defined as 2 consecutive HCV RNA measurements of >1 log10 IU/mL above nadir) at any time point during treatment~Failure to achieve HCV RNA < LLOQ by Week 6 or~Confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) at any point after HCV RNA < LLOQ during treatment after HCV RNA < LLOQ.~Participants in Arms B and E followed virologic stopping criteria described in the TPV Summary of Product Characteristics; they were considered virologic failures and discontinued therapy as follows:~HCV RNA > 1000 IU/mL at Week 4 to Week 12, discontinue TPV and pegIFN and RBV~HCV RNA > 1000 IU/mL at Week 12, discontinue pegIFN and RBV~Confirmed HCV RNA > lower limit of detection (LLOD) at Week 24, discontinue pegIFN and RBV~Confirmed HCV RNA > LLOD at Week 36, discontinue pegIFN and RBV." (NCT01854697)
Timeframe: 12 weeks for Arms A, C and D and 24 weeks or 48 weeks for Arms B and E
| Intervention | percentage of participants (Number) |
|---|
| Arm A: 3-DAA + RBV in GT1a | 2.9 |
| Arm B: TPV/PR in GT1a | 5.9 |
| Arm C: 3-DAA + RBV in GT1b | 0 |
| Arm D: 3-DAA in GT1b | 1.2 |
| Arm E: TPV/PR in GT1b | 12.2 |
Percentage of Participants With Post-treatment Relapse
Hepatitis C virus (HCV) ribonucleic acid (RNA) confirmed greater than or equal to the lower limit of quantification (LLOQ) between the end of treatment and 24 weeks post treatment among participants completing treatment and with HCV RNA less than the LLOQ at the end of treatment. (NCT01854697)
Timeframe: Within 24 weeks post treatment
| Intervention | percentage of participants (Number) |
|---|
| Arm A: 3-DAA + RBV in GT1a | 0 |
| Arm B: TPV/PR in GT1a | 0 |
| Arm C: 3-DAA + RBV in GT1b | 1.2 |
| Arm D: 3-DAA in GT1b | 0 |
| Arm E: TPV/PR in GT1b | 6.3 |
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. (NCT01854697)
Timeframe: 12 weeks after the last actual dose of active study drug
| Intervention | percentage of participants (Number) |
|---|
| Arm A: 3-DAA + RBV in GT1a | 97.1 |
| Arm B: TPV/PR in GT1a | 82.4 |
| Arm C: 3-DAA + RBV in GT1b | 98.8 |
| Arm D: 3-DAA in GT1b | 97.6 |
| Arm E: TPV/PR in GT1b | 78.0 |
Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24)
The percentage of participants with sustained virologic response (plasma HCV RNA level < LLOQ) 24 weeks after the last dose of study drug. (NCT01854697)
Timeframe: 24 weeks after the last actual dose of active study drug
| Intervention | percentage of participants (Number) |
|---|
| Arm A: 3-DAA + RBV in GT1a | 95.7 |
| Arm B: TPV/PR in GT1a | 82.4 |
| Arm C: 3-DAA + RBV in GT1b | 97.6 |
| Arm D: 3-DAA in GT1b | 97.6 |
| Arm E: TPV/PR in GT1b | 78.0 |
Percentage of Participants With SVR12 - Secondary Efficacy Analyses
The percentage of participants with sustained virologic response (plasma HCV RNA level < LLOQ) 12 weeks after the last dose of study drug. (NCT01854697)
Timeframe: 12 weeks after the last actual dose of active study drug
| Intervention | percentage of participants (Number) |
|---|
| Arm A: 3-DAA + RBV in GT1a | 97.1 |
| Arm B: TPV/PR in GT1a | 82.4 |
| Arm C: 3-DAA + RBV in GT1b | 98.8 |
| Arm D: 3-DAA in GT1b | 97.6 |
| Arm E: TPV/PR in GT1b | 78.0 |
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs
An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the participant at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above. (NCT01864148)
Timeframe: Up to 84 weeks
| Intervention | participants (Number) |
|---|
| Any event | Moderate or severe event | Severe event | BIIB033/placebo-related event | Avonex-related event | Serious event | BIIB033/placebo-related serious event | Avonex-related serious event | Event leading to discontinuation of treatment | Event leading to withdrawal from study |
|---|
| BIIB033 Total | 275 | 202 | 21 | 51 | 190 | 51 | 6 | 3 | 20 | 21 |
,| BIIB033, 10 mg/kg | 84 | 59 | 6 | 15 | 58 | 11 | 0 | 0 | 3 | 4 |
,| BIIB033, 100 mg/kg | 73 | 58 | 7 | 16 | 50 | 16 | 5 | 1 | 8 | 7 |
,| BIIB033, 3 mg/kg | 39 | 26 | 2 | 8 | 28 | 4 | 0 | 0 | 2 | 2 |
,| BIIB033, 30 mg/kg | 79 | 59 | 6 | 12 | 54 | 20 | 1 | 2 | 7 | 8 |
,| Placebo | 79 | 59 | 7 | 8 | 51 | 13 | 1 | 1 | 4 | 4 |
Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84
(NCT01864148)
Timeframe: Up to 84 weeks
| Intervention | µg/mL (Mean) |
|---|
| Baseline, predose; n=44, 95, 92, 92 | Baseline, postdose; n=44, 95, 91, 92 | Week 4, predose; n=45, 93, 91, 88 | Week 4, postdose; n=45, 94, 89, 85 | Week 8, predose; n=45, 95, 89, 85 | Week 8, postdose; n=44, 94, 88, 79 | Week 16, predose; n=43, 94, 86, 79 | Week 16, postdose; n=41, 93, 85, 78 | Week 24, predose; n=42, 93, 85, 74 | Week 24, postdose; n=42, 92, 82, 76 | Week 36, predose; n=41, 88, 79, 74 | Week 36, postdose; n=42, 88, 77, 73 | Week 48, predose; n=39, 85, 74, 70 | Week 48, postdose; n=42, 85, 75, 72 | Week 60, predose; n=41, 84, 70, 68 | Week 60, postdose; n=42, 84, 71, 71 | Week 72, predose; n=41, 85, 72, 68 | Week 72, postdose; n=38, 84, 69, 68 | Week 84; n=40, 81, 69, 69 |
|---|
| BIIB033, 10 mg/kg | 0.01 | 244.76 | 46.28 | 279.67 | 65.48 | 294.44 | 71.80 | 309.38 | 77.88 | 318.01 | 85.05 | 339.17 | 80.28 | 334.12 | 81.77 | 335.10 | 78.94 | 313.13 | 12.77 |
,| BIIB033, 100 mg/kg | 0.42 | 2298.20 | 457.96 | 2763.26 | 603.11 | 2751.25 | 695.11 | 2921.09 | 699.63 | 2870.29 | 725.22 | 3048.66 | 806.70 | 3167.07 | 694.12 | 3330.70 | 819.39 | 3145.82 | 127.69 |
,| BIIB033, 3 mg/kg | 0.00 | 66.70 | 10.82 | 123.96 | 23.55 | 86.29 | 19.96 | 85.95 | 36.41 | 144.12 | 25.33 | 94.62 | 20.78 | 90.07 | 21.29 | 93.11 | 19.53 | 82.96 | 2.44 |
,| BIIB033, 30 mg/kg | 7.79 | 688.47 | 138.54 | 784.08 | 195.29 | 861.60 | 231.94 | 881.45 | 230.46 | 940.29 | 238.48 | 197.86 | 272.88 | 955.25 | 243.18 | 939.17 | 215.09 | 868.39 | 46.16 |
Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint
Estimated proportion of participants experiencing confirmed clinical worsening in 1 or more components of the multicomponent endpoint (EDSS, T25FW, 9HPT, or PASAT-3) over 72 weeks, defined as: a ≥1.0 point increase in EDSS from a baseline score of ≤5.5 or a ≥0.5 point increase from a baseline score equal to 6.0 (increase sustained for 3 months or greater); a ≥15%worsening from baseline in time to complete T25FW test (worsening sustained for 3 months or greater), where the time is the average of 2 trials at the same visit; a ≥15% worsening from baseline in time to complete 9HPT by either hand (worsening sustained for 3 months or greater for the same hand), where the time is the average of 2 trials for each hand at the same visit; a ≥15% worsening from baseline in PASAT-3 score (worsening sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for MS type, region and baseline component assessments. (NCT01864148)
Timeframe: 72 weeks
| Intervention | proportion of participants (Number) |
|---|
| Placebo | 0.403 |
| BIIB033, 3 mg/kg | 0.304 |
| BIIB033, 10 mg/kg | 0.509 |
| BIIB033, 30 mg/kg | 0.489 |
| BIIB033, 100 mg/kg | 0.369 |
Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint
Estimated proportion of participants experiencing confirmed improvement in any 1 or more of the following components: a ≥1 point decrease in the Expanded Disability Status Scale (EDSS) score from a baseline score of <=6.0 (decrease sustained for ≥3 months); a ≥15% improvement from baseline in time to complete 9-Hole Peg Test (9HPT) by either hand (improvement sustained for ≥3 months for the same hand), where the time is the average time of 2 trials per hand at the same visit; a ≥15% improvement from baseline in time to complete Timed 25-Foot Walk (T25FW) test (improvement sustained for ≥3 months), where the time is the average time of 2 trials at the same visit; or a ≥15% improvement from baseline 3-Second Paced Auditory Serial Addition Test (PASAT-3) score (improvement sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for multiple sclerosis (MS) type, region and baseline component assessments. (NCT01864148)
Timeframe: 72 weeks
| Intervention | proportion of participants (Number) |
|---|
| Placebo | 0.516 |
| BIIB033, 3 mg/kg | 0.511 |
| BIIB033, 10 mg/kg | 0.656 |
| BIIB033, 30 mg/kg | 0.688 |
| BIIB033, 100 mg/kg | 0.412 |
Number of Participants With Treatment-emergent Grade 3/4 Lab Abnormalities
Grade 3/4 treatment-emergent lab abnormalities that occurred in >=5% of subjects in either cohort are reported. The analysis included all treated subjects up to the end of the treatment period (Day 1 to week 24, or Day 1 to week 48 for subjects requiring those visits). Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. AST = Aspartate aminotransferase, ALT = Alanine aminotransferase. (NCT01866930)
Timeframe: After Day 1 to end of treatment; up to Weeks 24 or 48
| Intervention | Participants (Count of Participants) |
|---|
| Total Bilirubin | AST | ALT |
|---|
| Cohort A: HCV GT-2 or GT-3 | 26 | 10 | 2 |
,| Cohort B: HCV GT-1 or GT-4 | 63 | 13 | 10 |
Number of Participants With Rapid Virologic Response (RVR) and Extended Rapid Virologic Response (eRVR)
RVR is defined as HCV RNA < LLOQ target not detected at Week 4 and eRVR defined as HCV RNA < LLOQ target not detected at Weeks 4 and 12 (NCT01866930)
Timeframe: Treatment weeks 4 and 12
| Intervention | Participants (Count of Participants) |
|---|
| RVR | eRVR |
|---|
| Cohort A: HCV GT-2 or GT-3 | 82 | 80 |
,| Cohort B: HCV GT-1 or GT-4 | 149 | 138 |
Number of Participants With On-treatment IFN-associated Flu-like or Musculoskeletal Symptoms
All treated participants were monitored for IFN-associated Flu-like and Musculoskeletal symptoms. Flu-like symptoms were defined as pyrexia, chills, or pain. Musculoskeletal symptoms were defined as arthralgia, myalgia, or back pain. Subjects were monitored throughout the treatment period during the treatment period (After day 1 up to week 24, or After day 1 up to week 48 for subjects requiring those visits). (NCT01866930)
Timeframe: After Day 1 to end of treatment; up to Weeks 24 or 48
| Intervention | Participants (Count of Participants) |
|---|
| Musculoskeletal symptoms | Flu-like symptoms |
|---|
| Cohort A: HCV GT-2 or GT-3 | 6 | 6 |
,| Cohort B: HCV GT-1 or GT-4 | 21 | 19 |
Number of Participants Who Died or Experienced Severe Adverse Events (SAEs), Dose Reductions of Lambda or Discontinuation Due to Adverse Events (AEs)
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that. at any dose, results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. (NCT01866930)
Timeframe: After Day 1 to end of treatment; up to Weeks 24 or 48
| Intervention | Participants (Count of Participants) |
|---|
| Deaths | SAEs | Lambda Dose Reduction | Discontinuation due to AEs |
|---|
| Cohort A: HCV GT-2 or GT-3 | 0 | 6 | 4 | 4 |
,| Cohort B: HCV GT-1 or GT-4 | 3 | 12 | 19 | 13 |
Number of Participants With Treatment Emergent Cytopenic Abnormalities
All treated participants were monitored for treatment emergent cytopenic abnormalities (anemia as defined by hemoglobin (Hb) < 10 g/dL, and/or neutropenia as defined by absolute neutrophil count (ANC) < 750 mm3 and/or thrombocytopenia as defined by platelets < 50,000/mm3) during the treatment period (Weeks 1, 2, 4, 6, 8, 12, 20, and 24, and at Weeks 28, 32, 36, 40, 44, and 48 for subjects requiring those visits). (NCT01866930)
Timeframe: After Day 1 to end of treatment; up to Weeks 24 or 48
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A: HCV GT-2 or GT-3 | 4 |
| Cohort B: HCV GT-1 or GT-4 | 15 |
Number of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12)
SVR12 was defined as HCV RNA less than lower limit of quantification (< LLOQ) (25 IU/mL; target detected or not detected) at follow-up week 12. (NCT01866930)
Timeframe: Follow-up week 12
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A: HCV GT-2 or GT-3 | 88 |
| Cohort B: HCV GT-1 or GT-4 | 149 |
Mean Percent Change in Total Lymphocyte Count From Baseline to End of Treatment
All treated participants were monitored for percent change in Total Lymphocyte Count from Baseline to the end of the treatment period. The mean percent change in each arm is presented for all evaluable participants. (NCT01866930)
Timeframe: Day 1 to end of treatment; up to week 24 or week 48
| Intervention | Percent change (Mean) |
|---|
| Cohort A: HCV GT-2 or GT-3 | -15.33 |
| Cohort B: HCV GT-1 or GT-4 | -22.95 |
Mean Percent Change in Absolute CD4 T Lymphocyte Count From Baseline to End of Treatment
All treated participants were monitored for percent change in CD4 T Lymphocyte count from Baseline to the end of the treatment period. The mean percent change in each arm is presented for all evaluable participants. (NCT01866930)
Timeframe: Day 1 to end of treatment; up to week 24 or week 48
| Intervention | Percent change (Mean) |
|---|
| Cohort A: HCV GT-2 or GT-3 | -4.0 |
| Cohort B: HCV GT-1 or GT-4 | -13.4 |
Mean Change in Total Lymphocyte Count From Baseline to End of Treatment
All treated participants were monitored for change in Total Lymphocyte Count from Baseline to the end of the treatment period. The mean change in each arm for all evaluable participants is reported in Cells/µL. (NCT01866930)
Timeframe: Day 1 to end of treatment; up to week 24 or week 48
| Intervention | Cells/µL (Mean) |
|---|
| Cohort A: HCV GT-2 or GT-3 | -0.38 |
| Cohort B: HCV GT-1 or GT-4 | -0.50 |
Mean Percent Change in Platelet Count From Baseline to End of Treatment
All treated participants were monitored for percent change in Platelet Count from Baseline to the end of the treatment period. The mean percent change in each arm is presented for all evaluable participants. (NCT01866930)
Timeframe: Day 1 to end of treatment; up to week 24 or week 48
| Intervention | Percent change (Mean) |
|---|
| Cohort A: HCV GT-2 or GT-3 | 16.9 |
| Cohort B: HCV GT-1 or GT-4 | 20.1 |
Mean Change in Absolute CD4 T Lymphocyte Count From Baseline to End of Treatment
All treated participants were monitored for change in Absolute CD4 T Lymphocyte count from Baseline to the end of the treatment period. The mean change in each arm for all evaluable participants is reported in Cells/µL. (NCT01866930)
Timeframe: Day 1 to end of treatment; up to week 24 or week 48
| Intervention | Cells/uL (Mean) |
|---|
| Cohort A: HCV GT-2 or GT-3 | -42.4 |
| Cohort B: HCV GT-1 or GT-4 | -104.9 |
Mean Change in Platelet Count From Baseline to End of Treatment
All treated participants were monitored for change in Platelet Count from Baseline to the end of the treatment period. The mean change in each arm for all evaluable participants (units of measurement = x10^9 cells/L). (NCT01866930)
Timeframe: Day 1 to end of treatment; up to week 24 or week 48
| Intervention | 10^9 cells/L (Mean) |
|---|
| Cohort A: HCV GT-2 or GT-3 | 32.7 |
| Cohort B: HCV GT-1 or GT-4 | 33.3 |
Frequency of Relapses in Patients Treated for up to 24 Months
Frequency of relapses assessed by the annualized relapse rate (ARR). The ARR is defined as the average number of confirmed relapses per year (total number of confirmed relapses divided by the total days in the study multiplied by 365.25). (NCT01892722)
Timeframe: 24 months
| Intervention | Confirmed relapse per year (Mean) |
|---|
| Fingolimod | 0.122 |
| Interferon Beta-1a | 0.675 |
Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
(NCT01925183)
Timeframe: Baseline (BL) to Follow-up week 12 (FU12)
| Intervention | Participants (Count of Participants) |
|---|
| Adverse events (AEs) | Serious adverse events (SAEs) |
|---|
| 28 Weeks of Treatment Duration | 3 | 0 |
,| 48 Weeks of Treatment Duration | 3 | 1 |
Proportion of Subjects With Sustained Virologic Response (SVR12)
Defined as HCV-RNA negativity by a sensitive assay (NCT01925183)
Timeframe: Follow-up week 12 (FU12)
| Intervention | Participants (Count of Participants) |
|---|
| 28 Weeks of Treatment Duration | 3 |
| 48 Weeks of Treatment Duration | 2 |
Change From Baseline in Copies of HIV DNA Per CD4+ T Cell at Week 24
Difference in copies of HIV DNA per CD4+ T cell between baseline and week 24, assessed by Alu-HIVgag polymerase chain reaction (NCT01935089)
Timeframe: Week 3 and 24
| Intervention | HIV DNA copies per CD4+ T cell (Median) |
|---|
| Baseline | Week 24 |
|---|
| Interferon Alpha | 113 | 98 |
Summary of Average Duration of FLS in the First 8 Weeks of Treatment
Duration of FLS for a treatment was defined as the sum of hours from the time of treatment to 48 hours with an FLS-S score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. If an FLS is > 0 at an evaluation time, 6 hours were counted as the duration assuming the event started from previous evaluation time. Average duration of FLS for the first 8 weeks was defined as the mean duration from Weeks 0, 2, 4, 6, and 8. 4WRI=4-week run-in period; F8W=first 8 weeks. (NCT01939002)
Timeframe: 4-week run-in period, first 8 weeks of treatment
| Intervention | hours (Median) |
|---|
| Average duration in 4WRI; n=88, 86, 174 | Average duration in F8W; n=91, 83, 174 | Change from 4WRI to F8W; n=85, 78, 163 |
|---|
| BIIB017 Plus Current FLS Therapy | 16 | 18 | 2.1 |
,| BIIB017 Plus Naproxen | 12.8 | 18 | 3.8 |
,| Overall Population | 13.75 | 18 | 3 |
Percentage of Participants With Any FLS in the 4-Week Run-In Period, During the First 8 Weeks of Treatment, and During 48 Weeks of Treatment
Any FLS is defined as an FLS-S total score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. 4WRI=4-week run-in; F8W=first 8 weeks; 48W=48 weeks. (NCT01939002)
Timeframe: 4-week run-in period, first 8 weeks of treatment, 48 weeks of treatment
| Intervention | percentage of participants (Number) |
|---|
| 4WRI | F8W | 48W |
|---|
| BIIB017 Plus Current FLS Therapy | 88 | 91 | 95 |
,| BIIB017 Plus Naproxen | 91.5 | 88.3 | 94.7 |
,| Overall Population | 89.7 | 89.7 | 94.8 |
Summary of Average Duration of FLS in the 48 Weeks of Treatment
Duration of FLS for a treatment was defined as the sum of hours from the time of treatment to 48 hours with a FLS-S score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. If a FLS is > 0 at an evaluation time, 6 hours were counted as the duration assuming the event started from previous evaluation time. Average duration of FLS for the first 8 weeks was defined as the mean duration from Weeks 0, 2, 4, 6, and 8. 4WRI=4-week run-in period; 48W=48 weeks. (NCT01939002)
Timeframe: 4-week run-in period, 48 weeks of treatment
| Intervention | hours (Median) |
|---|
| Average duration in 4WRI; n=88, 86, 174 | Average duration in 48W; n=95, 89, 184 | Change from 4WRI to 48W; n=86, 82, 168 |
|---|
| BIIB017 Plus Current FLS Therapy | 16 | 16.75 | 2.82 |
,| BIIB017 Plus Naproxen | 12.8 | 16.96 | 2 |
,| Overall Population | 13.75 | 16.96 | 2.16 |
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Effectiveness Scale Factor: Between FLS Management Arms
The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for effectiveness (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in. (NCT01939002)
Timeframe: 4-week run-in period, Week 4
| Intervention | units on a scale (Mean) |
|---|
| Effectiveness at 4WRI; n=100, 94 | Change at Week 4; n=95, 90 |
|---|
| BIIB017 Plus Current FLS Therapy | 75.16 | 0.979 |
,| BIIB017 Plus Naproxen | 72.5 | -6.356 |
Summary of FLS-Visual Analogue Scale (VAS) During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment
Participants reported the effectiveness of their FLS management regimen on a 100-mm VAS between not effective (0) and very effective (100). 4WRI=4-week run-in period; F8W=first 8 weeks. (NCT01939002)
Timeframe: 4-week run-in period, first 8 weeks of treatment
| Intervention | units on a scale (Mean) |
|---|
| Effectiveness in 4WRI; n=91, 86, 177 | Effectiveness in F8W; n=96, 91, 187 | Change from 4WRI to F8W; n=87, 83, 170 |
|---|
| BIIB017 Plus Current FLS Therapy | 64.5 | 69.695 | 6.525 |
,| BIIB017 Plus Naproxen | 66.398 | 74.253 | 5.694 |
,| Overall Population | 65.422 | 71.913 | 6.119 |
Summary of FLS-VAS During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment
Participants reported their satisfaction with the effectiveness of their FLS management regimen on a 100-mm VAS between not satisfied (0) and very satisfied (100). 4WRI=4-week run-in period; F8W=first 8 weeks. (NCT01939002)
Timeframe: 4-week run-in period, first 8 weeks of treatment
| Intervention | units on a scale (Mean) |
|---|
| Satisfaction in 4WRI; n=91, 86, 177 | Satisfaction in F8W; n=96, 91, 187 | Change from 4WRI to F8W; n=87, 83, 170 |
|---|
| BIIB017 Plus Current FLS Therapy | 68.654 | 71.153 | 3.715 |
,| BIIB017 Plus Naproxen | 72.778 | 74.684 | 0.759 |
,| Overall Population | 70.658 | 72.871 | 2.272 |
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Global Satisfaction Scale Factor: Between FLS Management Arms
The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for global satisfaction (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in. (NCT01939002)
Timeframe: 4-week run-in period, Week 4
| Intervention | units on a scale (Mean) |
|---|
| Global Satisfaction at 4WRI; n=100, 94 | Change at Week 4; n=95, 90 |
|---|
| BIIB017 Plus Current FLS Therapy | 75.86 | 8.663 |
,| BIIB017 Plus Naproxen | 76.117 | 4.811 |
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Side Effects Scale Factor: Between FLS Management Arms
The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for side effects (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in. (NCT01939002)
Timeframe: 4-week run-in period, Week 4
| Intervention | units on a scale (Mean) |
|---|
| Side Effects at 4WRI; n=100, 94 | Change at Week 4; n=95, 90 |
|---|
| BIIB017 Plus Current FLS Therapy | 83.78 | 8.579 |
,| BIIB017 Plus Naproxen | 86.649 | 3.411 |
Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs
An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could jeopardize the subject or could require intervention to prevent one of the other outcomes listed in the definition above. ISR=injection site reactions. (NCT01939002)
Timeframe: Day 1 to Week 52
| Intervention | participants (Number) |
|---|
| Any event | Moderate or severe event | Severe event | Related event | Serious event | Discontinuations due to AEs | Treatment discontinuation due to FLS event | Treatment discontinuation due to ISR events | Study discontinuation due to an event |
|---|
| BIIB017 Plus Current FLS Therapy | 93 | 54 | 7 | 80 | 4 | 14 | 3 | 5 | 13 |
,| BIIB017 Plus Naproxen | 90 | 60 | 12 | 71 | 6 | 13 | 2 | 3 | 13 |
Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to the First 8 Weeks
Any FLS is defined as an FLS-S total score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. Pre-dose data not were used. Data up to 48-hours after dosing were used. Total score was imputed as the highest score after dose. 4WRI=4-week run-in period; F8W=first 8 weeks. (NCT01939002)
Timeframe: 4-week run-in period, first 8 weeks of treatment
| Intervention | percentage of participants (Number) |
|---|
| With FLS in 4WRI / With FLS during F8W | With FLS in 4WRI / Without FLS during F8W | Without FLS in 4WRI / With FLS during F8W | Without FLS in 4WRI / Without FLS during F8W |
|---|
| BIIB017 Plus Current FLS Therapy | 85.00 | 3.00 | 6.00 | 6.00 |
,| BIIB017 Plus Naproxen | 82.98 | 8.51 | 5.32 | 3.19 |
,| Overall Population | 84.02 | 5.67 | 5.67 | 4.64 |
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Symptoms: Overall Population
Categorical questions in the Absenteeism Questionnaire asked participants to report the number of usual work days per week, the number of days missed in 2 weeks from MS symptoms, and the number of days missed in 2 weeks from MS treatment. This secondary endpoint was targeted to analyze the Overall Population only. 4WRI=4-week run-in. (NCT01939002)
Timeframe: Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination
| Intervention | days (Mean) |
|---|
| Days in 4WRI; n=123 | Change at Week 12; n=106 | Change at Week 24; n=99 | Change at Week 36; n=96 | Change at Week 48; n =95 | Change at Early Termination; n=15 |
|---|
| Overall Population | 0.016 | 0.057 | 0.061 | 0 | 0.137 | 0 |
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Treatment: Overall Population
Categorical questions in the Absenteeism Questionnaire asked participants to report the number of usual work days per week, the number of days missed in 2 weeks from MS symptoms, and the number of days missed in 2 weeks from MS treatment. This secondary endpoint was targeted to analyze the Overall Population only. 4WRI=4-week run-in. (NCT01939002)
Timeframe: Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination
| Intervention | days (Mean) |
|---|
| Days in 4WRI; n=123 | Change at Week 12; n=106 | Change at Week 24; n=99 | Change at Week 36; n=96 | Change at Week 48; n =95 | Change at Early Termination; n=15 |
|---|
| Overall Population | 0.016 | 0.019 | 0.02 | -0.021 | 0.126 | 0.2 |
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Usual Work Days Per Week: Overall Population
Categorical questions in the Absenteeism Questionnaire asked participants to report the number of usual work days per week, the number of days missed in 2 weeks from multiple sclerosis (MS) symptoms, and the number of days missed in 2 weeks from MS treatment. This secondary endpoint was targeted to analyze the Overall Population only. 4WRI=4-week run-in. (NCT01939002)
Timeframe: Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination
| Intervention | days (Mean) |
|---|
| Days in 4WRI; n=123 | Change at Week 12; n=106 | Change at Week 24; n=99 | Change at Week 36; n=96 | Change at Week 48; n=95 | Change at Early Termination; n=15 |
|---|
| Overall Population | 4.691 | -0.019 | -0.081 | -0.052 | 0.032 | 0.2 |
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population
The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for convenience (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in. (NCT01939002)
Timeframe: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination)
| Intervention | units on a scale (Mean) |
|---|
| Convenience at 4WRI; n=194 | Change at Week 4; n=185 | Change at Week 12; n=175 | Change at Week 24; n=167 | Change at Week 36; n =162 | Change at Week 48; n=153 | Change at Early Termination; n=26 |
|---|
| Overall Population | 66.665 | 18.703 | 18.12 | 18.419 | 18.704 | 19.588 | 7.808 |
Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment
Participants reported the effectiveness of their FLS management regimen on a 100-mm VAS between not effective (0) and very effective (100). 4WRI=4-week run-in period; 48W=48 weeks. (NCT01939002)
Timeframe: 4-week run-in period, 48 weeks of treatment
| Intervention | units on a scale (Mean) |
|---|
| Effectiveness in 4WRI; n=91, 86, 177 | Effectiveness in 48W; n=99, 94, 193 | Change from 4WRI to 48W; n=90, 86, 176 |
|---|
| BIIB017 Plus Current FLS Therapy | 64.5 | 70.547 | 6.803 |
,| BIIB017 Plus Naproxen | 66.398 | 75.416 | 8.042 |
,| Overall Population | 65.422 | 72.918 | 7.408 |
Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population
The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for effectiveness (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in. (NCT01939002)
Timeframe: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination)
| Intervention | units on a scale (Mean) |
|---|
| Effectiveness at 4WRI; n=194 | Change at Week 4; n=185 | Change at Week 12; n=175 | Change at Week 24; n=167 | Change at Week 36; n =162 | Change at Week 48; n=153 | Change at Early Termination; n=26 |
|---|
| Overall Population | 73.871 | -2.589 | -1.274 | 0.341 | 1.864 | 2.863 | -17.308 |
Change From Baseline Visit (Day 1) to Week 48 in Walking Disability Status as Measured by Patient Determined Disease Steps (PDDS): Overall Population
Subjects rated their perceived walking disability on a scale of 0 to 8 using the PDDS, with higher scores indicating more severe disability. This secondary endpoint was targeted to analyze the Overall Population only. (NCT01939002)
Timeframe: Day 1 (Baseline, pre-dose), Week 12, Week 48, Early Termination
| Intervention | units on a scale (Mean) |
|---|
| Baseline; n=194 | Change at Week 12; n=174 | Change at Week 48; n=153 | Change Early Termination; n=26 |
|---|
| Overall Population | 0.83 | 0.029 | 0.15 | 0.346 |
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing
The number of participants who tested positive for IFN β-1a Nabs. Value was coded as 'positive' if observed value > 0 or coded as 'negative' if observed value < 0. This secondary endpoint was targeted to analyze the Overall Population only. (NCT01939002)
Timeframe: Baseline (Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW)
| Intervention | participants (Number) |
|---|
| Baseline: Positive; n=22 | Baseline: Negative; n=22 | Any post-baseline visit: Positive; n=35 | Any post-baseline visit: Negative; n=35 | Week 12: Positive; n=26 | Week 12: Negative; n=26 | Week 24: Positive; n=22 | Week 24: Negative; n=22 | Week 36: Positive; n=18 | Week 36: Negative; n=18 | Week 48/EW: Positive; n=25 | Week 48/EW: Negative; n=25 | Negative at BL with ≥ 1 positive post-BL; n=7 |
|---|
| Overall Population | 14 | 8 | 17 | 20 | 15 | 11 | 11 | 11 | 11 | 7 | 12 | 13 | 1 |
Antibody Data in the Overall Population: IFN β-1a Antibody Screening
The number of participants who tested positive for IFN β-1a binding antibodies (BAbs). Value was coded as 'positive' if observed value > 0 or coded as 'negative' if observed value < 0. This secondary endpoint was targeted to analyze the Overall Population only. (NCT01939002)
Timeframe: Baseline (BL; Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW)
| Intervention | participants (Number) |
|---|
| Baseline: Positive; n=199 | Baseline: Negative; n=199 | Any post-baseline visit: Positive; n=198 | Any post-baseline visit: Negative; n=198 | Week 12: Positive; n=183 | Week 12: Negative; n=183 | Week 24: Positive; n=171 | Week 24: Negative; n=171 | Week 36: Positive; n=167 | Week 36: Negative; n=167 | Week 48/EW: Positive; n=193 | Week 48/EW: Negative; n=193 | Negative at BL with ≥ 1 positive post-BL; n=174 |
|---|
| Overall Population | 22 | 177 | 35 | 178 | 26 | 157 | 22 | 149 | 18 | 149 | 25 | 168 | 13 |
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing
The number of participants who tested positive or negative for IFN β-1a anti-PEG antibodies. Value was coded as 'positive' if observed value > 0 or coded as 'negative' if observed value < 0. This secondary endpoint was targeted to analyze the Overall Population only. (NCT01939002)
Timeframe: Baseline (BL; Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW)
| Intervention | participants (Number) |
|---|
| Baseline: Positive; n=201 | Baseline: Negative; n=201 | Any post-baseline visit: Positive; n=198 | Any post-baseline visit: Negative; n=198 | Week 12: Positive; n=182 | Week 12: Negative; n=182 | Week 24: Positive; n=173 | Week 24: Negative; n=173 | Week 36: Positive; n=168 | Week 36: Negative; n=168 | Week 48/EW: Positive; n=193 | Week 48/EW: Negative; n=193 | Negative at BL with ≥ 1 positive post-BL; n=192 |
|---|
| Overall Population | 7 | 194 | 8 | 196 | 6 | 176 | 3 | 170 | 1 | 167 | 3 | 190 | 4 |
Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Overall Population
The total Flu-like Symptoms Score (FLS-S) is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. New or increased FLS is defined as an FLS overall score of 2 points or greater over Screening. Pre-dose data were not used; up to 48-hour data after dosing were used. Overall score was imputed as the average score after dose. (NCT01939002)
Timeframe: during the first 8 weeks of treatment
| Intervention | percentage of participants (Number) |
|---|
| Overall Population | 10.3 |
Summary of Average Duration of FLS Within the Last 4 Weeks of the BIIB017 Treatment Period Compared With the Duration of FLS in the 4-Week Run-In Period
Average duration of FLS for the last 4 weeks (L4W) is defined as the mean duration of last 4 weeks. Duration of FLS for a treatment is defined as the sum of hours from the treatment to 48 hours with a FLS-S score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. If a FLS is > 0 at an evaluation time, 6 hours were counted as the duration assuming the event started from previous evaluation time. 4WRI=4-week run-in. (NCT01939002)
Timeframe: Weeks -4 to -1 (Screening), Weeks 45-48 (last 4 weeks of study)
| Intervention | hours (Mean) |
|---|
| Average duration in 4WRI; n=88, 86, 174 | Average duration in L4W; n=87, 83, 170 | Change from 4WRI to L4W; n=80, 77, 157 |
|---|
| BIIB017 Plus Current FLS Therapy | 16.067 | 18.057 | 2.612 |
,| BIIB017 Plus Naproxen | 14.915 | 15.892 | 0.943 |
,| Overall Population | 15.497 | 17 | 1.793 |
Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to 48 Weeks
Any FLS is defined as an FLS-S total score > 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. Pre-dose data not were used. Data up to 48-hours after dosing were used. Total score was imputed as the highest score after dose. 4WRI=4-week run-in period; 48W=48 weeks. (NCT01939002)
Timeframe: 4-week run-in period, 48 weeks of treatment
| Intervention | percentage of participants (Number) |
|---|
| With FLS in 4WRI / With FLS during 48W | With FLS in 4WRI / Without FLS during 48W | Without FLS in 4WRI / With FLS during 48W | Without FLS in 4WRI / Without FLS during 48W |
|---|
| BIIB017 Plus Current FLS Therapy | 86.00 | 2.00 | 9.00 | 3.00 |
,| BIIB017 Plus Naproxen | 87.23 | 4.26 | 7.45 | 1.06 |
,| Overall Population | 86.60 | 3.09 | 8.25 | 2.06 |
Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Between FLS Management Arms
The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. New or increased FLS is defined as an FLS overall score of 2 points or greater over Screening. Pre-dose data were not used; up to 48-hour data after dosing were used. Overall score was imputed as the average score after dose. (NCT01939002)
Timeframe: during the first 8 weeks of treatment
| Intervention | percentage of participants (Number) |
|---|
| BIIB017 Plus Current FLS Therapy | 13 |
| BIIB017 Plus Naproxen | 7.4 |
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Convenience Scale Factor: Between FLS Management Arms
The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for convenience (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in. (NCT01939002)
Timeframe: 4-week run-in period, Week 4
| Intervention | units on a scale (Mean) |
|---|
| Convenience at 4WRI; n=100, 94 | Change at Week 4; n=95, 90 |
|---|
| BIIB017 Plus Current FLS Therapy | 65.94 | 19.768 |
,| BIIB017 Plus Naproxen | 67.436 | 17.578 |
Summary of Severity of FLS (Per FLS-S) in the First 8 Weeks Compared to 4-Week Run-In Period Between Arms
The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. 4WRI=4-week run-in period; F8W=first 8 weeks. (NCT01939002)
Timeframe: 4-week run-in period, first 8 weeks of treatment
| Intervention | units on a scale (Mean) |
|---|
| Severity of FLS in 4WRI | Severity of FLS in F8W | Mean Change from 4WRI to F8W |
|---|
| BIIB017 Plus Current FLS Therapy | 1.198 | 1.311 | 0.113 |
,| BIIB017 Plus Naproxen | 1.05 | 1.036 | -0.013 |
,| Overall Population | 1.126 | 1.178 | 0.052 |
Summary of Severity of FLS (Per FLS-S) in the 48 Weeks of Treatment Compared to 4-Week Run-In Period Between Arms
The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. 4WRI=4-week run-in period; 48W=48 weeks. (NCT01939002)
Timeframe: 4-week run-in period, 48 weeks of treatment
| Intervention | units on a scale (Mean) |
|---|
| Severity of FLS in 4WRI | Severity of FLS in 48W | Mean Change from 4WRI to 48W |
|---|
| BIIB017 Plus Current FLS Therapy | 1.2 | 1.28 | 0.08 |
,| BIIB017 Plus Naproxen | 1.05 | 0.98 | -0.07 |
,| Overall Population | 1.13 | 1.14 | 0.01 |
Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment
Participants reported their satisfaction with the effectiveness of their FLS management regimen on a 100-mm VAS between not satisfied (0) and very satisfied (100). 4WRI=4-week run-in period; 48W=48 weeks. (NCT01939002)
Timeframe: 4-week run-in period, 48 weeks of treatment
| Intervention | units on a scale (Mean) |
|---|
| Satisfaction in 4WRI; n=91, 86, 177 | Satisfaction in 48W; n=99, 94, 193 | Change from 4WRI to 48W; n=90, 86, 176 |
|---|
| BIIB017 Plus Current FLS Therapy | 68.654 | 72.192 | 4.607 |
,| BIIB017 Plus Naproxen | 72.778 | 76.061 | 2.274 |
,| Overall Population | 70.658 | 74.076 | 3.467 |
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population
The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for global satisfaction (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in. (NCT01939002)
Timeframe: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination)
| Intervention | units on a scale (Mean) |
|---|
| Global Satisfaction at 4WRI; n=194 | Change at Week 4; n=185 | Change at Week 12; n=175 | Change at Week 24; n=167 | Change at Week 36; n =162 | Change at Week 48; n=153 | Change at Early Termination; n=26 |
|---|
| Overall Population | 75.985 | 6.789 | 7.354 | 7.575 | 9.179 | 8.556 | -38.538 |
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population
The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for side effects (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in. (NCT01939002)
Timeframe: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination)
| Intervention | units on a scale (Mean) |
|---|
| Side Effects at 4WRI; n=194 | Change at Week 4; n=185 | Change at Week 12; n=175 | Change at Week 24; n=167 | Change at Week 36; n=162 | Change at Week 48; n=153 | Change at Early Termination; n=26 |
|---|
| Overall Population | 85.17 | 6.065 | 5.109 | 2.958 | 3.37 | 1.418 | -18.731 |
Percentage of Participants With Undetectable HCV RNA Who Achieve Sustained Viral Response at Follow-up Week 12 (SVR12) [16-Week Arm vs. 28-Week Arm]
SVR12 was declared when participants who had undetectable HCV RNA (HCV RNA < Lower Limit of Quantification [LLoQ]) after the 12-week lead-in also had undetectable HCV RNA 12 weeks after completing their assigned BOC treatment regimen. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL. (NCT01945294)
Timeframe: Follow-up Week (FW) 12 (up to 40 weeks)
| Intervention | Percentage of Participants (Number) |
|---|
| Arm 1: 16-week Treatment Arm | 70.6 |
| Arm 2: 28-week Treatment Arm | 81.9 |
Percentage of Participants With Relapse
The percentage of viral relapse (defined as confirmed HCV RNA >15 IU/mL after End-of-Treatment [EOT]) among participants who had undetectable HCV RNA at EOT was determined for each arm. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL. (NCT01945294)
Timeframe: From EOT to FW12 (up to 12 weeks)
| Intervention | Percentage of Participants (Number) |
|---|
| Arm 1: 16-week Treatment Arm | 20.4 |
| Arm 2: 28-week Treatment Arm | 1.1 |
| Arm 3: 48-week Treatment Arm | 0.0 |
Percentage of Participants With Neutropenia
The percentage of participants with neutropenia (neutrophil count <0.75 x10^9/L) is summarized for each arm. (NCT01945294)
Timeframe: Up to 60 weeks
| Intervention | Percentage of Participants (Number) |
|---|
| Arm 1: 16-week Treatment Arm | 10.8 |
| Arm 2: 28-week Treatment Arm | 12.4 |
| Arm 3: 48-week Treatment Arm | 4.0 |
Percentage of Participants With Anemia
The percentage of participants with anemia (hemoglobin [Hgb] <10 g/dL) was determined in each arm. (NCT01945294)
Timeframe: Up to 60 weeks
| Intervention | Percentage of Participants (Number) |
|---|
| Arm 1: 16-week Treatment Arm | 33.3 |
| Arm 2: 28-week Treatment Arm | 43.8 |
| Arm 3: 48-week Treatment Arm | 26.0 |
Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment
The percentage of participants achieving SVR12 who had undetectable HCV RNA (HCV RNA NCT01945294)
Timeframe: TW4, TW8, and TW12
| Intervention | Percentage of Participants (Number) |
|---|
| % Undetectable HCV RNA at TW4 (n=25, 18, 0) | % Undetectable HCV RNA at TW8 (n=101, 104, 0) | % Undetectable HCV RNA at TW12 (n=100, 103, 20) |
|---|
| Arm 1: 16-week Treatment Arm | 24.5 | 69.6 | 68.6 |
,| Arm 2: 28-week Treatment Arm | 14.3 | 81.0 | 80.0 |
,| Arm 3: 48-week Treatment Arm | 0.0 | 0.0 | 41.4 |
Percentage of Participants With Undetectable HCV RNA Across Treatment
The percentage of participants with undetectable HCV RNA (HCV RNA NCT01945294)
Timeframe: TW4, TW8, and TW12
| Intervention | Percentage of Participants (Number) |
|---|
| TW4 | TW8 | TW12 |
|---|
| Arm 1: 16-week Treatment Arm | 24.8 | 100.0 | 99.0 |
,| Arm 2: 28-week Treatment Arm | 17.1 | 100.0 | 100.0 |
,| Arm 3: 48-week Treatment Arm | 0.0 | 0.0 | 69.0 |
Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The percentage of participants who discontinued from BOC, BOC + RBV, or all medications due to an AE are reported. (NCT01945294)
Timeframe: From TW1 through TW48
| Intervention | Percentage of Participants (Number) |
|---|
| Discontinued from BOC | Discontinued from BOC + R | Discontinued from all Study Medication |
|---|
| Arm 1: 16-week Treatment Arm | 2.9 | 0.0 | 0.0 |
,| Arm 2: 28-week Treatment Arm | 7.6 | 5.7 | 5.7 |
,| Arm 3: 48-week Treatment Arm | 16.0 | 8.0 | 8.0 |
Change in Class I Major Histocompatibility Complex (MHC) Expression After Treatment With IFN Gamma
It would be highly relevant to observe marked increase macrophages (effect size > 2.5). Four patients gives over 90% power to detect such a large increase with a two-tailed alpha of 0.05. (NCT01957709)
Timeframe: Baseline to up to 2 weeks post-surgery
| Intervention | percentage of MHC Class I+ on tumor cell (Median) |
|---|
| Pre-treatment | Post-treatment |
|---|
| Basic Science (Interferon Gamma and MHC Expression) | 8.91 | 26.6 |
MHC Class II Expression
To determine whether systemic administration of IFNg will increase class II MHC expression in SS and MRCL tumors. (NCT01957709)
Timeframe: Baseline to 2 weeks post biopsy.
| Intervention | percentage of MHC Class II on tumor cell (Median) |
|---|
| Pre-treatment | Post-treatment |
|---|
| Basic Science (Interferon Gamma and MHC Expression) | 2.556 | 6.125 |
Changes in Immune Response
To examine changes in the immune response to MRCL and SS by examining changes in the immune infiltrates, antibody response and antigen specific T cell response before and after IFNg treatment. (NCT01957709)
Timeframe: Baseline to 2 weeks post biopsy
| Intervention | percentage of T cells (Median) |
|---|
| Pre-treatment | Post-treatment |
|---|
| Basic Science (Interferon Gamma and MHC Expression) | 0.14 | 0.82 |
Change in Whole Blood Frataxin Levels
Assessment of the change in whole blood frataxin levels as assessed by lateral flow assay using an immunoassay for frataxin. Frataxin levels in the blood were measured at each study visit. Change in frataxin level at the end of treatment (week 12) relative to frataxin level at baseline was analyzed. (NCT01965327)
Timeframe: Frataxin levels were measured at the beginning and conclusion of treatment (baseline and 12 weeks)
| Intervention | percentage of baseline frataxin level (Mean) |
|---|
| Interferon Gamma-1b (ACTIMMUNE) | -1.5 |
Change in Total Friedreich Ataxia Rating Scale (FARS) Score
The Friedreich Ataxia Rating Scale (FARS) is neurological rating scale specifically developed and validated for FRDA. The FARS includes assessments of stance, gait, upper and lower limb coordination, speech, proprioception and strength. In addition to the standard neurological examination, the FARS contains three quantitative performance measures and a component that assesses activities of daily living (ADL). Quantitative performance measures include the nine-hole peg test, and a timed 25-foot walk. FARS scores correlate significantly with functional disability, activities of daily living scores and disease duration. The scores from the three subscales are added to generate a total score ranging from 0 to 159, with a higher score indicating a greater level of disability. (NCT01965327)
Timeframe: FARS score was calculated at the beginning and conclusion of treatment (baseline and 12 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Interferon Gamma-1b (ACTIMMUNE) | -4.98 |
Percent Change From Baseline in Normalized Brain Volume to Month 24 Based on Rank ANCOVA
"Brain volume (a measure of brain atrophy) was measured by brain MRI scans that were read at a centralized MRI reading facility by a blinded reader.~Due to the non-normal distribution of the data for brain volume loss, the analyses for percent change from Baseline in normalized brain volume was repeated using rank-analysis of covariance (ANCOVA) and observed values." (NCT02047734)
Timeframe: Baseline and Month 24
| Intervention | percent change (Median) |
|---|
| Interferon Beta-1a | -0.940 |
| Ozanimod 0.5 mg | -0.710 |
| Ozanimod 1 mg | -0.690 |
Percent Change From Baseline in Normalized Brain Volume to Month 24
Brain volume (a measure of brain atrophy) was measured by brain MRI scans that were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes. (NCT02047734)
Timeframe: Baseline and Month 24
| Intervention | percent change (Mean) |
|---|
| Interferon Beta-1a | -0.937 |
| Ozanimod 0.5 mg | -0.707 |
| Ozanimod 1 mg | -0.707 |
Change From Baseline to Month 24 in Multiple Sclerosis Functional Composite (MSFC) Score Including the Low-Contrast Letter Acuity (LCLA) Test
"The MSFC-LCLA is a battery including the following 4 individual scales:~Timed 25-Foot Walk is an ambulation measure of walking 25 feet with time taken recorded in seconds~9-Hole Peg Test (9HPT) is a quantitative measure of upper extremity (arm and hand) function~Symbol Digit Modalities Test (SDMT) is a measure of executive cognitive function that assesses processing speed, flexibility, and calculation ability~Low-Contrast Letter Acuity Test (LCLA) used a standardized set of charts to assess low contrast visual acuity, charts are scored according to the number of letters that are identified correctly~Z-scores were calculated for for each component and averaged to create an overall composite score, using the study population as the reference population. A Z-score represents the number of standard deviations a patient's test result is higher (Z > 0) or lower (Z < 0) than the average test result (Z = 0) of the reference population. A positive change indicates improvement." (NCT02047734)
Timeframe: Baseline to Month 24
| Intervention | Z-score (Mean) |
|---|
| Interferon Beta-1a | -0.052 |
| Ozanimod 0.5 mg | 0.036 |
| Ozanimod 1 mg | -0.010 |
Adjusted Mean Number of New or Enlarging Hyperintense T2-Weighted Brain Magnetic Resonance Imaging (MRI) Lesions Per Scan Over 24 Months
"The adjusted mean number of new or enlarging hyperintense T2-weighted brain MRI lesions per scan was based on the cumulative number of new or enlarging T2 lesions since Baseline over 24 months. MRI images were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.~The adjusted mean per scan over 24 months was based based on a negative binomial regression model using observed data, adjusted for region (Eastern Europe vs. Rest of the World), age at Baseline, and Baseline number of GdE lesions. The natural log transformation of the number of available MRI scans over 24 months is used as an offset term." (NCT02047734)
Timeframe: 24 month treatment period; MRI scans were performed at Months 12 and 24
| Intervention | lesions/scan (Least Squares Mean) |
|---|
| Interferon Beta-1a | 3.183 |
| Ozanimod 0.5 mg | 2.092 |
| Ozanimod 1 mg | 1.835 |
Adjusted Mean Number of Gadolinium Enhancing Brain Lesions at Month 24
"MRI images were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.~The number of gadolinium-enhancing (GdE) lesions at 24 months was analyzed based on observed data using a negative binomial regression model adjusted for region (Eastern Europe vs Rest of World), Baseline age, and Baseline number of GdE lesions, with natural log transformation of number of available MRI scans over 24 months as an offset term (1 scan for per participant)." (NCT02047734)
Timeframe: Month 24
| Intervention | lesions (Least Squares Mean) |
|---|
| Interferon Beta-1a | 0.373 |
| Ozanimod 0.5 mg | 0.197 |
| Ozanimod 1 mg | 0.176 |
Number of Participants With Treatment Emergent Adverse Events
"An adverse event (AE) is any untoward medical occurrence that does not necessarily have a causal relationship with the investigational product (IP), including an abnormal laboratory finding, symptom or disease temporally associated with the use of an IP whether or not considered related to the IP. Serious AEs were events that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, were congenital abnormalities/birth defects, or important medical events which may have required medical intervention to prevent one of the above outcomes.~The investigator assessed the severity of AEs as mild, moderate, or severe and the relationship of each AE to treatment as unrelated, unlikely, possible, probable, or related based on timing and other known factors such as clinical state, environment, or other therapies." (NCT02047734)
Timeframe: From the first dose of study drug up to the first dose of the open-label extension study RPC01-3001, or up to 28 days after last dose for participants who did not continue into the open-label extension study; median duration of treatment was 24 months.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Any Moderate or Severe TEAE | Any Severe TEAE | Any Related TEAE | Any Serious TEAE | Any Related Serious TEAE | Any TEAE Leading to discontinuation of Study Drug | Any TEAE Leading to Study Withdrawal | Any Death on Study |
|---|
| Interferon Beta-1a | 365 | 235 | 19 | 30 | 28 | 0 | 18 | 20 | 0 |
,| Ozanimod 0.5 mg | 326 | 169 | 19 | 12 | 31 | 1 | 14 | 13 | 1 |
,| Ozanimod 1 mg | 324 | 170 | 15 | 19 | 28 | 1 | 13 | 13 | 0 |
Mean Change From Baseline in Multiple Sclerosis Quality of Life (MSQOL)-54 Physical Health Composite Summary and Mental Health Composite Summary Scores
"The MSQOL-54 is a multidimensional health-related QOL measure that combines both generic and MS-specific items into a single instrument. The instrument includes 12 subscales, two summary scores, and two single-item measures.~The two summary scores - physical health and mental health - are derived from a weighted combination of scale scores.~The physical health composite score includes Physical function, Health perceptions, Energy/fatigue, Role limitations - physical, Pain, Sexual function, Social function, and Health distress.~The mental health composite score includes Health distress, Overall quality of life, Emotional well-being, Role limitations - emotional, and Cognitive function.~Each composite summary score has a range from 0 to 100 where higher scores indicate better quality of life. A positive change from Baseline indicates improvement." (NCT02047734)
Timeframe: Baseline to Month 24
| Intervention | units on a scale (Mean) |
|---|
| Physical Health Composite Summary | Mental Health Composite Summary |
|---|
| Interferon Beta-1a | -1.526 | -1.831 |
,| Ozanimod 0.5 mg | 0.609 | -1.182 |
,| Ozanimod 1 mg | 0.209 | -1.517 |
Time to Onset of Disability Progression Confirmed After 6 Months
"EDSS is used to quantify disability and disability progression over time in MS. Based on a neurological examination, 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, and other functions) are scored from 0 (no disability) to 5 or 6 (more severe disability). Ambulation is assessed based on distance the patient is able to walk, whether assistance is required or restrictions are present.~The EDSS score ranges from 0 (normal) to 10 (death due to MS) in 0.5 unit increments.~Disability progression is defined by a sustained worsening in EDSS score of 1.0 point or more confirmed after 3 months. Time to onset of disability progression was calculated from the date of first dose to the date of the first visit at which the 1.0 point increase in EDSS was met using Kaplan-Meier methods. Participants without a sustained disease progression event were censored on the date of their last assessment or last dose of study drug, whichever was later." (NCT02047734)
Timeframe: From first dose to the end of the 24-month treatment period
| Intervention | days (Median) |
|---|
| Interferon Beta-1a | NA |
| Ozanimod 0.5 mg | NA |
| Ozanimod 1 mg | NA |
Time to Onset of Disability Progression Confirmed After 3 Months
"EDSS is used to quantify disability and disability progression over time in MS. Based on a neurological examination, 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, and other functions) are scored from 0 (no disability) to 5 or 6 (more severe disability). Ambulation is assessed based on distance the patient is able to walk, whether assistance is required or restrictions are present.~The EDSS score ranges from 0 (normal) to 10 (death due to MS) in 0.5 unit increments.~Disability progression is defined by a sustained worsening in EDSS score of 1.0 point or more confirmed after 3 months. Time to onset of disability progression was calculated from the date of first dose to the date of the first visit at which the 1.0 point increase in EDSS was met using Kaplan-Meier methods. Participants without a sustained disease progression event were censored on the date of their last assessment or last dose of study drug, whichever was later." (NCT02047734)
Timeframe: From first dose to the end of the 24-month treatment period
| Intervention | days (Median) |
|---|
| Interferon Beta-1a | NA |
| Ozanimod 0.5 mg | NA |
| Ozanimod 1 mg | NA |
Percentage of Participants Who Were New or Enlarging T2 Lesion-Free at Month 24
MRI images were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes. (NCT02047734)
Timeframe: Month 24
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a | 18.4 |
| Ozanimod 0.5 mg | 23.5 |
| Ozanimod 1 mg | 23.8 |
Percentage of Participants Who Were Gadolinium Enhancing (GdE) Lesion-Free at Month 24
"Participants were considered lesion free at Month 24 if they did not show evidence of GdE lesions at the Month 24 MRI scan.~MRI images were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes." (NCT02047734)
Timeframe: Month 24
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a | 56.2 |
| Ozanimod 0.5 mg | 63.3 |
| Ozanimod 1 mg | 65.6 |
Adjusted Annualized Relapse Rate (ARR) at the End of Month 24
"A relapse was defined as new or worsening neurological symptoms attributable to MS and preceded by a relatively stable or improving neurological state for at least 30 days. Symptoms must have persisted for > 24 hours and not be attributable to confounding clinical factors. Relapses were confirmed when accompanied by objective neurological worsening based on examination by the blinded evaluator, consistent with an increase of ≥ 0.5 on the overall EDSS score relative to the most recent EDSS assessment, or 2 points on one of the functional system scale scores, or 1 point on ≥ two functional system scale scores.~Relapse rate was calculated as the total number of confirmed relapses divided by the total number of days in the study * 365.25.~ARR was based on a Poisson regression model, adjusted for region (Eastern Europe vs Rest of the World), age, and the Baseline number of gadolinium-enhancing lesions, and included the natural log transformation of time on study as an offset term." (NCT02047734)
Timeframe: At the end of month 24
| Intervention | relapses/year (Number) |
|---|
| Interferon Beta-1a | 0.276 |
| Ozanimod 0.5 mg | 0.218 |
| Ozanimod 1 mg | 0.172 |
Number of Participants With Shifts From Baseline in Hematology
Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. (NCT02097849)
Timeframe: Screening to Week 4
| Intervention | participants (Number) |
|---|
| Hemoglobin: Shift to Low; n=28, 36 | Hemoglobin: Shift to High; n=32, 38 | Hematocrit: Shift to Low; n=31, 37 | Hematocrit: Shift to High; n=32, 38 | Red Blood Cell Count: Shift to Low; n=25, 32 | Red Blood Cell Count: Shift to High; n=33, 37 | White Blood Cell Count: Shift to Low; n=27, 30 | White Blood Cell Count: Shift to High; n=33, 38 | Neutrophils: Shift to Low; n=27, 34 | Neutrophils: Shift to High; n=33, 37 | Basophils: Shift to Low; n=33, 38 | Basophils: Shift to High; n=33, 38 | Monocytes: Shift to Low; n=33, 38 | Monocytes: Shift to High; n=33, 38 | Lymphocytes: Shift to Low; n=33, 22 | Lymphocytes: Shift to High; n=33, 38 | Eosinophils: Shift to Low; n=33, 38 | Eosinophils: Shift to High; n=33, 38 | Platelet Count: Shift to Low; n=31, 38 | Platelet Count: Shift to High; n=32, 37 |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 1 | 0 | 2 | 0 | 1 | 0 | 2 | 2 | 3 | 2 | 0 | 0 | 0 | 2 | 4 | 0 | 0 | 0 | 1 | 0 |
,| Tecfidera Treated Plus Vaccinations | 0 | 0 | 1 | 0 | 4 | 0 | 4 | 0 | 2 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With Shifts From Baseline in Blood Chemistry
Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high. (NCT02097849)
Timeframe: Screening to Week 4
| Intervention | participants (Number) |
|---|
| Alanine Aminotransferase: Shift to Low; n=33, 38 | Alanine Aminotransferase: Shift to High; n=30, 35 | Aspartate Aminotransferase: Shift to Low; n=33, 37 | Aspartate Aminotransferase: Shift to High; n=33,36 | Total Bilirubin: Shift to Low; n=32, 37 | Total Bilirubin: Shift to High; n=33, 38 | Gamma-glutamyl Transferase: Shift to Low; n=33, 38 | Gamma-glutamyl Transferase: Shift to High; n=33,38 | Blood Urea Nitrogen: Shift to Low; n=33, 38 | Blood Urea Nitrogen: Shift to High; n=33, 38 | Creatinine: Shift to Low; n=33, 38 | Creatinine: Shift to High; n=33, 37 | Sodium: Shift to Low; n=33, 38 | Sodium: Shift to High; n=33, 38 | Potassium: Shift to Low; n=33, 38 | Potassium: Shift to High; n=33, 38 | Chloride: Shift to Low; n=33, 38 | Chloride: Shift to High; n=33, 38 |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
,| Tecfidera Treated Plus Vaccinations | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With Abnormalities in Vital Signs
Temperature increase: > 38 celcius (C) or ≥ 1 C increase from baseline. Pulse increase: > 120 beats per minute (bpm) or > 20 bpm increase from baseline. Pulse decrease: < 50 bpm or > 20 bpm decrease from baseline. Systolic blood pressure (SBP) increase: > 180 millimeters of mercury (mmHg) or > 40 mmHg from baseline. SBP decrease: < 90 mmHg or > 30 mmHg decrease from baseline. Diastolic blood pressure (DBP) increase: > 105 mmHg or > 30 mmHg increase from baseline. DBP decrease: < 50 mmHg or > 20 mmHg decrease from baseline. (NCT02097849)
Timeframe: Screening to Week 4
| Intervention | participants (Number) |
|---|
| Temperature Increase | Pulse Increase | Pulse Decrease | SBP Increase | SBP Decrease | DBP Increase | DBP Decrease |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
,| Tecfidera Treated Plus Vaccinations | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
Ratio of Serum Tetanus Level at Day 28 to Prevaccination
Median serum titer ratios from prevaccination to 4 weeks after Td vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | ratio (Median) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 6.128 |
| Tecfidera Treated Plus Vaccinations | 4.463 |
Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs
An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. A serious AE was any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the participant or required intervention to prevent one of the other outcomes listed in the definition above. (NCT02097849)
Timeframe: Day 1 to Week 4
| Intervention | participants (Number) |
|---|
| Any Event | Moderate or Severe Event | Severe Event | Event Related to Existing Therapy | Serious Event | Serious Event Related to Existing Therapy | Serious Event Related to Td Vaccine | Serious Event Related to PPSV23 Vaccine | Serious Event Related to MCV4 Vaccine | Withdrew From Study Due to an Event |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 18 | 9 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Tecfidera Treated Plus Vaccinations | 16 | 7 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
Ratio of Serum Pneumococcal Antibodies (Serotype 3) Level at Day 28 to Prevaccination
Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | ratio (Median) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 9.667 |
| Tecfidera Treated Plus Vaccinations | 4.741 |
Percentage of Pneumococcal Serotype 8 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level
Percentage of participants with a ≥ 2-fold rise in anti-pneumococcal serum IgG levels against serotype 8 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | percentage of participants (Number) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 88 |
| Tecfidera Treated Plus Vaccinations | 95 |
Percentage of Pneumococcal Serotype 8 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level
Percentage of participants with a ≥ 4-fold rise in anti-pneumococcal serum IgG levels against serotype 8 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | percentage of participants (Number) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 85 |
| Tecfidera Treated Plus Vaccinations | 82 |
Percentage of Tetanus Responders (≥ 2-Fold Rise) at Day 28 Compared to Prevaccination Level
Percentage of participants with a ≥ 2-fold rise in anti-tetanus serum immunoglobulin G (IgG) levels (responders) from prevaccination to 4 weeks after Td vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | percentage of participants (Number) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 73 |
| Tecfidera Treated Plus Vaccinations | 68 |
Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level
Percentage of participants with a ≥ 4-fold rise in anti-tetanus serum IgG levels (responders) from prevaccination to 4 weeks after Td vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | percentage of participants (Number) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 61 |
| Tecfidera Treated Plus Vaccinations | 42 |
Percentage of Meningococcal Serogroup C Responders (≥ 4-Fold Rise) Compared to Prevaccination Level
Percentage of participants with a ≥ 4-fold rise in anti-meningococcal serum IgG levels against serotype C from prevaccination to 4 weeks after MCV4 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | percentage of participants (Number) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 38 |
| Tecfidera Treated Plus Vaccinations | 37 |
Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level
Percentage of participants with a ≥ 2-fold rise in anti-pneumococcal serum IgG levels against serotype 3 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | percentage of participants (Number) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 79 |
| Tecfidera Treated Plus Vaccinations | 66 |
Percentage of Meningococcal Serogroup C Responders (≥ 2-Fold Rise) Compared to Prevaccination Level
Percentage of participants with a ≥ 2-fold rise in anti-meningococcal serum IgG levels against serotype C from prevaccination to 4 weeks after MCV4 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | percentage of participants (Number) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 53 |
| Tecfidera Treated Plus Vaccinations | 53 |
Percentage of Pneumococcal Serotype 3 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level
Percentage of participants with a ≥ 4-fold rise in anti-pneumococcal serum IgG levels against serotype 3 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | percentage of participants (Number) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 70 |
| Tecfidera Treated Plus Vaccinations | 47 |
Ratio of Serum Meningococcal Antibodies (Serogroup C) Level at Day 28 to Prevaccination
Median serum titer ratios from prevaccination to 4 weeks after MCV4 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | ratio (Median) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 3.300 |
| Tecfidera Treated Plus Vaccinations | 3.408 |
Ratio of Serum Pneumococcal Antibodies (Serotype 8) Level at Day 28 to Prevaccination
Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination. (NCT02097849)
Timeframe: Up to Week 4 (Day 28) postvaccination
| Intervention | ratio (Median) |
|---|
| Non-Pegylated IFN Treated Plus Vaccinations | 27.000 |
| Tecfidera Treated Plus Vaccinations | 13.845 |
Percentage of Participants With Sustained Virologic Response (SVR)
SVR is defined as HCV-PCR assay result below limit of detection or viral load ≤50 IU/ml and/or qualitatively negative at least 12 weeks after the end of treatment at follow up. Follow-up visit occurred at 12 to 24 weeks following discontinuation of treatment. (NCT02106156)
Timeframe: Up to Week 96
| Intervention | percentage of participants (Number) |
|---|
| Main Analysis Set | 41.4 |
| Elastography Analysis Set: Treated | 36.7 |
Duration of Peginterferon Alfa-2a Therapy
Treatment duration was evaluated for participants for whom dates of treatment start and end of therapy were documented. (NCT02106156)
Timeframe: Up to Week 72
| Intervention | weeks (Median) |
|---|
| Main Analysis Set | 27.3 |
| Elastography Analysis Set: Treated | 29.3 |
Percentage Cumulative Dose of Peginterferon Alfa-2a Received
Data for the accumulation of the cumulative dose of peginterferon alfa-2a were analyzed and reported as the percentage of the intended dose participants received. Cumulative doses were evaluated for participants for whom dosage data were documented consistently throughout the observational period. If the treatment was ongoing at the study end, the cumulative dose was aggregated for the documented observational period. (NCT02106156)
Timeframe: Up to Week 96
| Intervention | percentage of cumulated dose (Median) |
|---|
| Main Analysis Set | 97.9 |
| Elastography Analysis Set: Treated | 94.8 |
Percentage Cumulative Dose of Ribavirin Received
Data for the accumulation of the cumulative dose of ribavirin were analyzed and reported as the percentage of the intended dose participants received. Cumulative doses were evaluated for participants for whom dosage data were documented consistently throughout the observational period. If the treatment was ongoing at the study end, the cumulative dose was aggregated for the documented observational period. (NCT02106156)
Timeframe: Up to Week 96
| Intervention | percentage of cumulated dose (Median) |
|---|
| Main Analysis Set | 100.00 |
| Elastography Analysis Set: Treated | 97.92 |
Percentage of Participants With Early Virologic Response (EVR)
EVR is defined as HCV-PCR assay result qualitatively negative and/or decline of viral load of ≥2 log levels and/or viral load ≤50 IU/ml at Week 12. (NCT02106156)
Timeframe: At Week 12
| Intervention | percentage of participants (Number) |
|---|
| Main Analysis Set | 71.2 |
| Elastography Analysis Set: Treated | 77.8 |
Percentage of Participants With End of Treatment (EOT) Response
EOT Response is defined as HCV-PCR assay result below limit of detection or viral load ≤50 IU/ml and/or qualitatively negative at the end of treatment. (NCT02106156)
Timeframe: Up to Week 72
| Intervention | percentage of participants (Number) |
|---|
| Main Analysis Set | 59.2 |
| Elastography Analysis Set: Treated | 51.1 |
Percentage of Participants With Rapid Virologic Response (RVR)
RVR is defined as Hepatitis C-Virus (HCV) Polymerase Chain Reaction (PCR) assay result qualitatively negative and/or viral load ≤50 International Units/milliliter (IU/ml) at Week 4. (NCT02106156)
Timeframe: At Week 4
| Intervention | percentage of participants (Number) |
|---|
| Main Analysis Set | 40.0 |
| Elastography Analysis Set: Treated | 41.7 |
Percentage of Participants With Serious Adverse Drug Reactions (SADR)
(NCT02106156)
Timeframe: Up to Week 96
| Intervention | percentage of participants (Number) |
|---|
| Main Analysis Set | 3.5 |
| Elastography Analysis Set: Treated | 3.3 |
Percentage of Participants With the Most Frequent Concomitant Medications
Most frequent concomitant medications were defined as those, which were observed in >1 % of participants. (NCT02106156)
Timeframe: At Baseline (Day 1)
| Intervention | percentage of participants (Number) |
|---|
| Anilides | Selective serotonin reuptake inhibitors | Proton pump inhibitors | Propionic acid derivatives | Propulsives | Other antidepressants | Angiotensin-converting-enzyme (ACE) inhibitors | Thyroid hormones | Corticosteroids, potent (group III) | Benzodiazepine related drugs | Pyrazolones | Beta blocking agents, selective | Non-selective monoamine reuptake inhibitors |
|---|
| Main Analysis Set | 10.6 | 9.9 | 5.3 | 4.7 | 2.3 | 2.3 | 2.0 | 1.8 | 1.7 | 1.5 | 1.4 | 1.3 | 1.2 |
Percentage of Participants With Virological Response
Virological response is defined as HCV RNA <15 IU/mL. (NCT02118597)
Timeframe: Weeks 4, 8, 12, and 24
| Intervention | percentage of participants (Number) |
|---|
| Week 4 (n=3) | Week 8 (n=18) | Week 12 (n=17) | Week 24 (n=16) |
|---|
| Triple Combination Therapy | 0.0 | 73.7 | 73.7 | 78.9 |
Number of Participants With Treatment Discontinuation
Treatment discontinuation is reported by sub-categories of reasons for treatment discontinuation. Futility rule is defined as HCV RNA drop <3 log10 at Week 8, HCV RNA >/=100 IU/mL at Week 12, or HCV RNA >/=15 IU/mL at Week 24. (NCT02118597)
Timeframe: Up to Week 48
| Intervention | participants (Number) |
|---|
| Sponsor's decision | Adverse event | Futility rule |
|---|
| Triple Combination Therapy | 7 | 4 | 2 |
Number of Participants With Virological Relapse
Virological response is defined as HCV RNA >/=15 IU/mL during the treatment free follow-up period in participants with virological response at the end of treatment. (NCT02118597)
Timeframe: Week 49 up to Week 72
| Intervention | participants (Number) |
|---|
| Triple Combination Therapy | 1 |
Number of Participants With Virological Breakthrough
Virological breakthrough is defined as either HCV RNA >=15 IU/mL in participants with prior virological response or as an increase in HCV RNA >/=1 log10 above nadir. (NCT02118597)
Timeframe: Up to Week 48
| Intervention | participants (Number) |
|---|
| Triple Combination Therapy | 1 |
Number of Participants With Treatment Discontinuation Due to Futility
Treatment discontinuation due to futility is defined as HCV RNA drop <3 log10 at Week 8, HCV RNA >/=100 IU/mL at Week 12, or HCV RNA >/=15 IU/mL at Week 24. (NCT02118597)
Timeframe: Up to Week 48
| Intervention | participants (Number) |
|---|
| Triple Combination Therapy | 2 |
Number of Participants With Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. (NCT02118597)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Triple Combination Therapy | 17 |
Sustained Virological Response 24 (SVR24) Rate
The SVR 24 rate is defined as percentage of participants with Hepatitis C virus (HCV) Ribonucleic Acid (RNA) less than 15 international unit/milliliter (IU/mL) after the 24-weeks follow-up. (NCT02118597)
Timeframe: 24 weeks after end of treatment (EOT) at Week 72
| Intervention | percentage of participants (Number) |
|---|
| Triple Combination Therapy | 0 |
Time to Progression (TTP)
The length of time from the start of treatment until disease progression, per RECIST 1.1 considering only patients whose deaths were from cancer. Disease progression per RECIST 1.1 Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). (NCT02151448)
Timeframe: Up to18 months
| Intervention | months (Median) |
|---|
| α DC1 Vaccine + Chemokine Modulatory Regimen | 15.9 |
CXCL10 (Interferon Gamma-induced Protein 10) Levels
Chemokine CXCL10 (Interferon gamma-induced protein 10) concentration levels measures in peripheral blood as a biomarker of anti-tumor activity. Increased levels can be predictive of good prognosis. (NCT02151448)
Timeframe: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
| Intervention | pg/mL (Mean) |
|---|
| Prior to vaccine administration (Week 1) | Prior to vaccine booster (Week 4) | After vaccine booster (Week 8) |
|---|
| α DC1 Vaccine + Chemokine Modulatory Regimen | 1221.5 | 16335.0 | 137.6 |
CXCL11 (C-X-C Motif Chemokine 11) Levels
CXCL11 (C-X-C motif chemokine 11) protein concentration levels measures in peripheral blood. Increased levels can be predictive of good prognosis. (NCT02151448)
Timeframe: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
| Intervention | pg/mL (Mean) |
|---|
| Prior to vaccine administration (Week 1) | Prior to vaccine booster (Week 4) | After vaccine booster (Week 8) |
|---|
| α DC1 Vaccine + Chemokine Modulatory Regimen | 359.4 | 12893.2 | 208.9 |
Interleukin 10 (IL-10) Levels
Interleukin 10 (IL-10) (human cytokine synthesis inhibitory factor (CSIF)) concentration levels measures in peripheral blood. Increased levels of IL-10 is associated with advanced disease and poor prognosis. (NCT02151448)
Timeframe: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
| Intervention | pg/ml (Mean) |
|---|
| Prior to vaccine administration (Week 1) | Prior to vaccine booster (Week 4) | After vaccine booster (Week 8) |
|---|
| α DC1 Vaccine + Chemokine Modulatory Regimen | 1.2 | 7.9 | 7.5 |
Interleukin 6 (IL-6) Cytokine Levels
Interleukin 6 (IL-6) concentration levels measures in peripheral blood. Increased levels of IL-6 is associated with associated with advanced disease and poor prognosis. (NCT02151448)
Timeframe: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
| Intervention | pg/mL (Mean) |
|---|
| Prior to vaccine administration (Week 1) | Prior to vaccine booster (Week 4) | After vaccine booster (Week 8) |
|---|
| α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen | 15.2 | 32.8 | 11.1 |
Interleukin-8 (IL-8) Cytokine Levels
Interleukin-8 (IL-8) cytokine concentration levels measures in peripheral blood. Increased levels of IL-8 is associated with associated with advanced disease and poor prognosis. (NCT02151448)
Timeframe: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
| Intervention | pg/mL (Mean) |
|---|
| Prior to vaccine administration (Week 1) | Prior to vaccine booster (Week 4) | After vaccine booster (Week 8) |
|---|
| α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen | 9.5 | 16.9 | 28.6 |
Overall Survival (OS)
The length of time from the start of treatment that diagnosed patients are still alive. (NCT02151448)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| α DC1 Vaccine + Chemokine Modulatory Regimen | 52 |
Progression-free Survival (PFS)
The length of time during and after the treatment that patients remain alive with disease that does not progress. Per RECIST 1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). (NCT02151448)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| colon cancer | appendiceal cancer | Mesothelioma |
|---|
| α DC1 Vaccine + Chemokine Modulatory Regimen | 19 | 16 | NA |
Stromal Derived Factor 1 Alpha (SDF-1A/CXCL-12) Chemokine Levels
Levels of stromal derived factor 1 alpha (SDF-1A/CXCL-12) chemokine in peripheral blood. Higher levels of SDF-1A/CXCL-12 is associated with good prognosis. (NCT02151448)
Timeframe: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
| Intervention | pg/mL (Mean) |
|---|
| Prior to vaccine administration (Week 1) | Prior to vaccine booster (Week 4) | After vaccine booster (Week 8) |
|---|
| α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen | 1267.3 | 2160.3 | 510.0 |
Tumor Necrosis Factor (TFNα) Cytokine Levels
Tumor necrosis factor (TFNα) cytokine concentration levels measures in peripheral blood. Higher TFNα levels is associated with good prognosis. (NCT02151448)
Timeframe: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
| Intervention | pg/mL (Mean) |
|---|
| Prior to vaccine administration (Week 1) | Prior to vaccine booster (Week 4) | After vaccine booster (Week 8) |
|---|
| α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen | 10.8 | 31.0 | 17.2 |
Percentage of Participants Experiencing Adverse Events (AEs)
An adverse event was any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. (NCT02155322)
Timeframe: From first dose through follow-up; up to 13 months
| Intervention | Percentage of participants (Number) |
|---|
| PEG-IFN | 100.0 |
Percentage of Participants Discontinuing Study Drug Because of AEs
An adverse event was any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. (NCT02155322)
Timeframe: From first dose to last dose of treatment; up to 12 months
| Intervention | Percentage of participants (Number) |
|---|
| PEG-IFN | 3.1 |
Proportion of Clinical Responders (Complete Response + Partial Response)
Response determination will be made according to the RECIST criteria. Complete response defined as the disappearance of target lesion, confirmed at 1-4 weeks. Partial response defined as 30% decrease in longest dimension of target lesion, confirmed at 1-4 weeks. (NCT02159482)
Timeframe: 4 weeks
| Intervention | percentage of participants (Number) |
|---|
| Interferon-alfa-2a | 0 |
Proportion of Patients Experiencing an Increase in the Magnitude of the Tumor Antigen-specific Immune Response
The proportion of patients experiencing an increase in the magnitude of the tumor antigen-specific immune response following the administration of interferon will also be estimated. Immune response will be determined by ELISPOT analysis. (NCT02159482)
Timeframe: 4 weeks
| Intervention | percentage of participants (Number) |
|---|
| Interferon-alfa-2a | 60 |
Serum HCV RNA Level
(NCT02168361)
Timeframe: 4 and 12 weeks into therapy
| Intervention | IU/ml (Median) |
|---|
| Serum HCV RNA level at 4 weeks | Serum HCV RNA level at 8 weeks |
|---|
| All Oral Therapy | 154 | 31 |
,| Interferon-containing Arm | 880 | 740 |
Proportion of Participants With Sustained Virologic Response 12 (SVR-12)
Undetectable virus (sensitive nucleic acid test) in Serum at 3 months post-therapy (NCT02168361)
Timeframe: 12 weeks post-therapy
| Intervention | participants (Number) |
|---|
| All Oral Therapy | 54 |
| Interferon-containing Arm | 18 |
Overall Survival (OS)
OS: The time from registration to death or date of last contact. Participants with overall survival at 1 year. Kaplan-Meier estimator will be utilized. (NCT02218164)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Expired in less than a year | Alive at the end of the year | Had not completed survival follow-up at closeout |
|---|
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | 4 | 2 | 2 |
Objective Response Rate (ORR)
ORR: Stable Disease (SD); Partial Response (PR); Complete Response (CR). Response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR: disappearance of all target lesions; PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. (NCT02218164)
Timeframe: 9 weeks per participant
| Intervention | Participants (Count of Participants) |
|---|
| Stable Disease | Complete Response | Partial Response |
|---|
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | 4 | 1 | 1 |
Progression Free Survival (PFS)
PFS: Alive without RECIST progression. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. (NCT02218164)
Timeframe: 1 year
| Intervention | months (Median) |
|---|
| Capecitabine or 5-FU With Pegylated Interferon Alpha-2b | 11.3 |
Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80%
Number of participants with ribavirin compliance at ≥ 95%, 80% - 95%, and < 80%. (NCT02247440)
Timeframe: From initiation of treatment to the first 48 weeks of treatment
| Intervention | Participants (Count of Participants) |
|---|
| Week 0 to Week 271963978 | Week 2 to Week 471963978 | Week 4 to Week 1271963978 | Week 12 to Week 1671963978 | Week 16 to Week 2071963978 | Week 20 to Week 2471963978 | Week 24 to Week 2871963978 | Week 28 to Week 3271963978 | Week 32 to Week 3671963978 | Week 36 to Week 4471963978 | Week 44 to Week 4871963978 |
|---|
| Compliance < 80% | Compliance ≥ 95% | Compliance 80% - 95% |
|---|
| PegINF-ribavirin | 0 |
| PegINF-ribavirin | 1 |
| PegINF-ribavirin | 17 |
| PegINF-ribavirin | 16 |
| PegINF-ribavirin | 15 |
| PegINF-ribavirin | 2 |
| PegINF-ribavirin | 13 |
| PegINF-ribavirin | 14 |
Number of Participants With at Least a Serious Adverse Events Associated With Study Treatment (Peg-interferon and Ribavirin)
Number of participants with at least a serious adverse events associated with study treatment (peg-interferon and ribavirin). (NCT02247440)
Timeframe: From initiation of treatment to 6 months after treatment discontinuation
| Intervention | Participants (Count of Participants) |
|---|
| PegINF-ribavirin | 1 |
Number of Participants With Sustained Virological Response 6 Months After Treatment Discontinuation
Number of Participants with Sustained Virological Response 6 Months After Treatment Discontinuation, (NCT02247440)
Timeframe: 6 months after end of treatment, i.e. 1.5 years after treatment initiation
| Intervention | Participants (Count of Participants) |
|---|
| PegINF-ribavirin | 10 |
Number of Adverse Events by Severity Grade
Number of adverse events (AE) by severity grade. The severity grading scale is based on the DAIDS grading table, the grading scale ranging from grades 1 to 5: Grade 1 indicates a mild event, Grade 2 indicates a moderate event, Grade 3 indicates a severe event, Grade 4 indicates a potentially life-threatening event, and Grade 5 indicates death. (NCT02247440)
Timeframe: From initiation of treatment to 6 months after treatment discontinuation
| Intervention | events (Number) |
|---|
| AE grade 1 | AE grade 2 | AE grade 3 |
|---|
| PegINF-ribavirin | 18 | 7 | 1 |
Number of Participants Grouped by HIV-1 RNA Concentrations
Number of participants grouped by HIV-1 RNA concentrations (Detected vs. Not Detected). (NCT02247440)
Timeframe: At time of treatment discontinuation (whatever its date) and 6 months thereafter
| Intervention | Participants (Count of Participants) |
|---|
| HIV-1 RNA not detected | HIV-1 RNA detected | Missing |
|---|
| PegINF-ribavirin | 16 | 1 | 1 |
Number of Participants Completed the First 24 and 48 Weeks of Treatment
Number of participants completed the first 24 and 48 weeks of treatment. (NCT02247440)
Timeframe: From initiation of treatment to the first 48 weeks of treatment
| Intervention | Participants (Count of Participants) |
|---|
| Completed the first 24 weeks of treatment | Completed the first 48 weeks of treatment |
|---|
| PegINF-ribavirin | 14 | 14 |
Healthcare Resource Utilization Questionnaire - Number of Subjects Who Missed Any Partial Days From Work Due to Multiple Sclerosis (MS).
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of subjects who missed any partial days from work due to MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | subjects (Number) |
|---|
| Rebif In RMS Subjects | 1 |
| Rebif in CIS Subjects | 2 |
Number of Subjects With Medication Adherence Based on Morisky Medication Adherence Score
The Morisky Medication Adherence Scale (MMAS) is a valid and reliable instrument that consists of 8 items that measure medication adherence. The scores of the MMAS-8 range from 0 to 8. This self-report scale consists of 7 items answered with a yes or no and 1 item with a 5-point Likert scale. A score below 6 indicates low adherence, a score between 6 to < 8 indicates medium adherence and a score of 8 indicates high adherence. (NCT02254304)
Timeframe: Month 12
| Intervention | subjects (Number) |
|---|
| Low Adherence | Medium Adherence | High Adherence |
|---|
| Rebif in CIS Subjects | 3 | 6 | 8 |
,| Rebif In RMS Subjects | 23 | 45 | 21 |
Healthcare Resource Utilization Questionnaire - Number of Full Days Missed From Work by Subjects
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of full days missed from work by subjects were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | days (Mean) |
|---|
| Rebif In RMS Subjects | 46.5 |
| Rebif in CIS Subjects | 3.5 |
Healthcare Resource Utilization Questionnaire - Number of Days Per Week Assistant Worked For Subject Due to Multiple Sclerosis (MS)
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of days per week assistant worked for subject due to MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | days per week (Mean) |
|---|
| Rebif In RMS Subjects | 2.5 |
| Rebif in CIS Subjects | 2.0 |
Number of Subjects With Reasons of Missed Injections
Number of subjects with the reasons of missed injections were presented. Aspartate transaminase and alanine transaminase are abbreviated as ALT and AST respectively. Glutamic oxaloacetic transaminase and glutamic pyruvic transaminase are abbreviated as GOT and GPT respectively. (NCT02254304)
Timeframe: Baseline up to 12 months
| Intervention | subjects (Number) |
|---|
| Forgot to Injection | Tired | Fear of Injection | Did not want to have Injection | Pain at Injection site | Flu-like symptoms | Adverse event | Device broken | Device malfunctions | Device not functioning | Difficulty using the device | Elevated ALT and AST | Elevated liver enzymes | Increased GOT and GPT levels | Local erythema and induration | Missed study medication | Forgot the device at home | No access to medication | could not came at the scheduled visit | Patient redrawn intracutaneous | Stop the treatment | Technical problems with Rebismart |
|---|
| Rebif In RMS and CIS Subjects | 48 | 23 | 11 | 5 | 5 | 4 | 2 | 1 | 1 | 1 | 1 | 1 | 2 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Healthcare Resource Utilization Questionnaire - Number of Times Subjects Visited Emergency Room Due to Multiple Sclerosis (MS)
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of times subjects visited emergency room due to MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | emergency room visits (Mean) |
|---|
| Rebif In RMS Subjects | 0.0 |
| Rebif in CIS Subjects | 0.0 |
Healthcare Resource Utilization Questionnaire - Number of Visits to Clinic by Subjects Due to Multiple Sclerosis (MS)
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of visits to clinic by subjects due to MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | visits (Mean) |
|---|
| Rebif In RMS Subjects | 0.2 |
| Rebif in CIS Subjects | 0.1 |
Percentage of Subjects With Treatment Adherence
According to the World Health Organisation (WHO), treatment adherence is defined as both compliance (taking the medication in the correct dose and according to the schedule prescribed) and persistency (maintenance of the drug regimen over the long-term). Percentage of subjects with treatment adherence under different categories (<=50%, >50-75%, >75-90%, >90%) were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | percentage of subjects (Number) |
|---|
| Adherence <=50% | Adherence >50-75% | Adherence >75-90% | Adherence >90% | Missing |
|---|
| Rebif in CIS Subjects | 11.8 | 0.0 | 0.0 | 88.2 | 0.0 |
,| Rebif In RMS Subjects | 2.2 | 2.2 | 13.5 | 80.9 | 1.1 |
Percentage of Subjects With Relapse by Adherence Category
A relapse was defined as the appearance of a new symptom or worsening of an old symptom, attributable to multiple sclerosis (MS), accompanied by an appropriate new neurological abnormality or focal neurological dysfunction lasting at least 24 hours in the absence of fever, and preceded by stability or improvement for at least 30 days. According to the World Health Organisation (WHO), treatment adherence is defined as both compliance (taking the medication in the correct dose and according to the schedule prescribed) and persistency (maintenance of the drug regimen over the long-term). Percentage of subjects with relapses by adherence categories (<=50%, >50-75%, >75-90%, >90%) were presented. Adherence missing are the subjects who withdrew before 12 months and who did not have any relapses before withdrawal. (NCT02254304)
Timeframe: Month 12
| Intervention | percentage of subjects (Number) |
|---|
| Relapse Status Yes, Adherence <= 50% | Relapse Status Yes, Adherence >90% | Relapse Status No, Adherence <= 50% | Relapse Status No, Adherence >90% | Relapse Status Missing, Adherence <=50% | Relapse Status Missing, Adherence >75-90% | Relapse Status Missing, Adherence >90% |
|---|
| Rebif in CIS Subjects | 0.0 | 6.7 | 50.0 | 73.3 | 50.0 | 0.0 | 20.0 |
Percentage of Subjects With Relapse by Adherence Category
A relapse was defined as the appearance of a new symptom or worsening of an old symptom, attributable to multiple sclerosis (MS), accompanied by an appropriate new neurological abnormality or focal neurological dysfunction lasting at least 24 hours in the absence of fever, and preceded by stability or improvement for at least 30 days. According to the World Health Organisation (WHO), treatment adherence is defined as both compliance (taking the medication in the correct dose and according to the schedule prescribed) and persistency (maintenance of the drug regimen over the long-term). Percentage of subjects with relapses by adherence categories (<=50%, >50-75%, >75-90%, >90%) were presented. Adherence missing are the subjects who withdrew before 12 months and who did not have any relapses before withdrawal. (NCT02254304)
Timeframe: Month 12
| Intervention | percentage of subjects (Number) |
|---|
| Relapse Status Yes, Adherence <= 50% | Relapse Status Yes, Adherence >50-75% | Relapse Status Yes, Adherence >75-90% | Relapse Status Yes, Adherence >90% | Relapse Status Yes, Adherence Missing | Relapse Status No, Adherence <= 50% | Relapse Status No, Adherence >50-75% | Relapse Status No, Adherence >75-90% | Relapse Status No, Adherence >90% | Relapse Status No, Adherence Missing | Relapse Status Missing, Adherence <=50% | Relapse Status Missing, Adherence >50-75% | Relapse Status Missing, Adherence >75-90% | Relapse Status Missing, Adherence >90% | Relapse Status Missing, Adherence Missing |
|---|
| Rebif In RMS Subjects | 0.0 | 0.0 | 16.7 | 19.4 | 0.0 | 0.0 | 50.0 | 50.0 | 72.2 | 0.0 | 100.0 | 50.0 | 33.3 | 8.3 | 100.0 |
Percentage of Subjects Who Prematurely Terminated Treatment and Reasons
Percentage of subjects who prematurely terminated treatment and reasons were presented. (NCT02254304)
Timeframe: Baseline up to 12 months
| Intervention | percentage of subjects (Number) |
|---|
| Adverse Event | Lost to follow-up | Protocol Non-compliance | Withdrew Consent | Pain at Injection site and fear of Injection | Personal causes | Personal decision |
|---|
| Rebif in CIS Subjects | 5.9 | 11.8 | 0.0 | 0.0 | 0.0 | 5.9 | 0.0 |
,| Rebif In RMS Subjects | 2.2 | 2.2 | 1.1 | 3.4 | 1.1 | 4.5 | 1.1 |
Healthcare Resource Utilization Questionnaire - Number of Visits by Healthcare Professional to Subjects' Home
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of visits by healthcare professional to subjects' home were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | visits (Mean) |
|---|
| Rebif In RMS Subjects | 0.0 |
| Rebif in CIS Subjects | 0.0 |
Overall Evaluation of RebiSmart Use as Assessed by Investigator
Evaluation of RebiSmart was categorized under very easy, quite easy, Neither easy nor difficult, very difficult and missing (NCT02254304)
Timeframe: Month 12
| Intervention | subjects (Number) |
|---|
| Very easy | Quite easy | Neither easy nor difficult | Quite difficult | Very difficult | Missing |
|---|
| Rebif in CIS Subjects | 13 | 1 | 1 | 0 | 2 | 0 |
,| Rebif In RMS Subjects | 46 | 32 | 9 | 0 | 1 | 1 |
Healthcare Resource Utilization Questionnaire - Number of Working Days Missed by Relative or Friend Due to Subjects' Multiple Sclerosis (MS)
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of working days missed by relative or friend due to subjects' MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | days (Mean) |
|---|
| Rebif In RMS Subjects | 1 |
| Rebif in CIS Subjects | 3 |
Healthcare Resource Utilization Questionnaire - Number of Subjects Whose Relatives or Friends Missed Work Due to Subjects' Multiple Sclerosis (MS)
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of subjects whose relatives or friends missed work due to subjects' MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | subject (Number) |
|---|
| Rebif In RMS Subjects | 1 |
| Rebif in CIS Subjects | 1 |
Healthcare Resource Utilization Questionnaire -Number of Subjects Who Paid Someone to Assist Them Due to Multiple Sclerosis (MS)
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of subjects who paid someone to assist them due to MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | subjects (Number) |
|---|
| Rebif In RMS Subjects | 2 |
| Rebif in CIS Subjects | 1 |
Mean Number of Relapses in RMS Subjects
A relapse was defined as the appearance of a new symptom or worsening of an old symptom, attributable to multiple sclerosis (MS), accompanied by an appropriate new neurological abnormality or focal neurological dysfunction lasting at least 24 hours in the absence of fever, and preceded by stability or improvement for at least 30 days. (NCT02254304)
Timeframe: Month 12
| Intervention | relapses (Mean) |
|---|
| Rebif In RMS Subjects | 0.2 |
Healthcare Resource Utilization Questionnaire - Number of Days Subjects Hospitalized Due to Multiple Sclerosis (MS)
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of days subjects hospitalized due to MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | days (Mean) |
|---|
| Rebif In RMS Subjects | 0.1 |
| Rebif in CIS Subjects | 0.0 |
Healthcare Resource Utilization Questionnaire - Number of Subjects Accomplished Less Work Due to Multiple Sclerosis (MS)
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of subjects accomplished less work due to MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | subjects (Number) |
|---|
| Rebif In RMS Subjects | 7 |
| Rebif in CIS Subjects | 1 |
Healthcare Resource Utilization Questionnaire - Number of Hours Per Day Missed From Work by Subjects
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of hours per day missed from work by subjects were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | hours per day (Mean) |
|---|
| Rebif In RMS Subjects | 8.0 |
| Rebif in CIS Subjects | 3.0 |
Healthcare Resource Utilization Questionnaire - Number of Subjects Who Missed Any Full Days From Work Due to Multiple Sclerosis (MS).
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of subjects who missed any full days from work due to MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | subjects (Number) |
|---|
| Rebif In RMS Subjects | 2 |
| Rebif in CIS Subjects | 2 |
Healthcare Resource Utilization Questionnaire - Number of Hours Per Day Assistant Worked for Subject Due to Multiple Sclerosis (MS)
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of hours per week assistant worked for subject due to MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | hours per day (Mean) |
|---|
| Rebif In RMS Subjects | 2.0 |
| Rebif in CIS Subjects | 4.0 |
Percentage of Relapse-free RMS Subjects
"A relapse was defined as the appearance of a new symptom or worsening of an old symptom, attributable to multiple sclerosis (MS), accompanied by an appropriate new neurological abnormality or focal neurological dysfunction lasting at least 24 hours in the absence of fever, and preceded by stability or improvement for at least 30 days. Relapse-free RMS subjects were those who did not had relapse during 12 month treatment period. Data was planned to be reported for Rebif in RMS Subjects arm." (NCT02254304)
Timeframe: Month 12
| Intervention | percentage of subjects (Number) |
|---|
| Rebif In RMS Subjects | 66.3 |
Time to the First Relapse for CIS Subjects
"A relapse was defined as the appearance of a new symptom or worsening of an old symptom, attributable to MS, accompanied by an appropriate new neurological abnormality or focal neurological dysfunction lasting at least 24 hours in the absence of fever, and preceded by stability or improvement for at least 30 days. Time to the first relapse was defined as the duration from start of the treatment until first relapse. Data was planned to be reported for Rebif in CIS Subjects arm." (NCT02254304)
Timeframe: Baseline up to 12 months
| Intervention | months (Median) |
|---|
| Rebif in CIS Subjects | NA |
Body Mass Index (BMI)
BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2). (NCT02254304)
Timeframe: Baseline, Month 12
| Intervention | Kg/m^2 (Mean) |
|---|
| Baseline | Month 12 |
|---|
| Rebif In RMS and CIS Subjects | 23.57 | 23.51 |
Expanded Disability Status Scale (EDSS) Score
EDSS is an ordinal scale in half-point increments that qualifies disability in participants with MS. It consists of 8 ordinal rating scales assessing seven functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS). (NCT02254304)
Timeframe: Baseline, Month 12
| Intervention | Units on a scale (Mean) |
|---|
| Baseline | Month 12 |
|---|
| Rebif in CIS Subjects | 1.24 | 1.13 |
,| Rebif In RMS Subjects | 1.87 | 1.80 |
Healthcare Resource Utilization Questionnaire - Number of Subjects Visiting Different Types of Doctors During Their Clinical Visit
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Subjects who took consultations with specialists, general practitioners for MS were presented. (NCT02254304)
Timeframe: Month 12
| Intervention | subjects (Number) |
|---|
| General practitioner | Specialist |
|---|
| Rebif in CIS Subjects | 1 | 0 |
,| Rebif In RMS Subjects | 1 | 15 |
Healthcare Resource Utilization Questionnaire - Number of Subjects With Percentage of Work Completed Despite of Multiple Sclerosis (MS)
Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Amount of work done by subjects in spite of multiple sclerosis was presented under different percentages (0-100%) (NCT02254304)
Timeframe: Month 12
| Intervention | Subjects (Number) |
|---|
| 0% Work Completed | 10% Work Completed | 20% Work Completed | 30% Work Completed | 40% Work Completed | 50% Work Completed | 60% Work Completed | 70% Work Completed | 80% Work Completed | 90% Work Completed | 100% Work Completed |
|---|
| Rebif in CIS Subjects | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
,| Rebif In RMS Subjects | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 3 | 2 | 0 |
Number of Subjects With Adverse Event or Adverse Drug Reaction (AE/ADR), Serious AE/ADR, AE/ADR Leading to Death and AE/ADR Leading to Early Termination
An AE was any untoward medical occurrence in a subject or clinical investigation in a subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An ADR was any unfavourable or unintended response (adverse event) that could possibly be related to drug treatment. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. AE/ADR was planned to be reported for both the arms together. (NCT02254304)
Timeframe: Baseline up to 12 months
| Intervention | subjects (Number) |
|---|
| AE/ADR | Serious AE/ADR | AE/ADR Leading to Death | AE/ADR Leading to Early Termination |
|---|
| Rebif | 30 | 1 | 0 | 4 |
Percentage of Participants With Loss of HBsAg
This endpoint is defined as loss of HBsAg at 1 year post-treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 3.8 |
Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation
This endpoint is defined as loss of HBsAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80). The percentage of responders (response rate) and 95% CI (using the Clopper-Pearson method) for the response rate are presented for each group. (NCT02263079)
Timeframe: 24 weeks post-treatment/at the end of untreated observation (Week 80)
| Intervention | Percentage of Participants (Number) |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 3.8 |
| Untreated Control Participants | 0 |
Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)
This endpoint is defined as loss of HBeAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| 24 Weeks post-treatment/Week 80 |
|---|
| Untreated Control Participants | 12.1 |
Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA)
This endpoint measures different HBV DNA levels (<20000 IU/mL, <2000 IU/mL and undetectable) measured by PCR or hybridization at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-treatment in the treated group. HBV-DNA undetectable is defined as <29 IU/mL. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| HBV-DNA <20000 IU/mL at follow up Week 24/Week 80 | HBV-DNA <2000 IU/mL at follow up Week 24/Week 80 | HBV-DNA Undetectable at follow up Week 24/Week 80 | HBV-DNA <20000 IU/mL 1 year post-end of treatment | HBV-DNA <2000 IU/mL 1 year post-end of treatment | HBV-DNA Undetectable 1 year post-end of treatment |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 7.7 | 7.7 | 0.0 | 15.4 | 7.7 | 0.0 |
Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA)
This endpoint measures different HBV DNA levels (<20000 IU/mL, <2000 IU/mL and undetectable) measured by PCR or hybridization at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-treatment in the treated group. HBV-DNA undetectable is defined as <29 IU/mL. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| HBV-DNA <20000 IU/mL at follow up Week 24/Week 80 | HBV-DNA <2000 IU/mL at follow up Week 24/Week 80 | HBV-DNA Undetectable at follow up Week 24/Week 80 |
|---|
| Untreated Control Participants | 12.1 | 12.1 | 6.1 |
Change From Baseline in HBV DNA Levels in the Untreated Control Participants
This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Untreated Control arm. (NCT02263079)
Timeframe: Baseline, Week 32, 56 and end of untreated observation (Week 80)
| Intervention | log10 IU/mL (Mean) |
|---|
| Baseline | Week 32 | Week 56 | Week 80 |
|---|
| Untreated Control Participants | 8.22 | 8.29 | 7.57 | 7.24 |
Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL
This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels <2000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| 24 Weeks post-treatment/Week 80 |
|---|
| Untreated Control Participants | 9.1 |
Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL
This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels <20,000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| 24 Weeks post-treatment/Week 80 | 1 year post-end of treatment |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 0.0 | 7.7 |
Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL
This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels <20,000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| 24 Weeks post-treatment/Week 80 |
|---|
| Untreated Control Participants | 9.1 |
Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL
This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels <2000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| 24 Weeks post-treatment/Week 80 | 1 year post-end of treatment |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 0.0 | 7.7 |
Percentage of Participants With Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. (NCT02263079)
Timeframe: Baseline up to 24 weeks post-treatment/end of untreated observation (Week 80)
| Intervention | Percentage of Participants (Number) |
|---|
| With at least one Non-Serious AE | With at least one Serious Adverse Event (SAE) |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 92.3 | 0 |
,| Untreated Control Participants | 45.5 | 3.0 |
Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe
This endpoint measures the seroconversion to anti-HBe defined as loss of HBeAg and presence of anti-HBe at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| 24 Weeks post-treatment/Week 80 |
|---|
| Untreated Control Participants | 9.1 |
Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe
This endpoint measures the seroconversion to anti-HBe defined as loss of HBeAg and presence of anti-HBe at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| 24 Weeks post-treatment/Week 80 | 1 year post-end of treatment |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 0.0 | 7.7 |
Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)
This endpoint is defined as loss of HBeAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| 24 Weeks post-treatment/Week 80 | 1 year post-end of treatment |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 3.8 | 11.5 |
Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs
This endpoint measures the seroconversion to anti-HBs defined as loss of HBsAg and presence of anti-HBs at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| 24 Weeks post-treatment/Week 80 |
|---|
| Untreated Control Participants | 0.0 |
Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs
This endpoint measures the seroconversion to anti-HBs defined as loss of HBsAg and presence of anti-HBs at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. (NCT02263079)
Timeframe: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
| Intervention | Percentage of Participants (Number) |
|---|
| 24 Weeks post-treatment/Week 80 | 1 year post-end of treatment |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 3.8 | 3.8 |
Serum Concentration of Peg-INF-Alfa-2A
The serum concentration of Peg-INF-Alfa-2A was measured in picogram/milliliter. (NCT02263079)
Timeframe: At Weeks 12, 16, 20, 32, 44, 56
| Intervention | pg/mL (Mean) |
|---|
| Week 12 Predose | Week 16 Predose | Week 20 Predose | Week 32 Predose | Week 32 24-48h Post-dose | Week 32 72-96h Post-dose | Week 32 168h Post-dose | Week 44 Predose | Week 56 Predose |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 8430 | 16300 | 13800 | 14900 | 22700 | 23000 | 19300 | 21900 | 25400 |
Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm
This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Peg-INF-Alfa-2A + Lamivudine or Entecavir arm. (NCT02263079)
Timeframe: Baseline, Week 8, 20, 32, 44, 56, Follow up Week 4 and 24
| Intervention | log10 IU/mL (Mean) |
|---|
| Baseline | Week 8 | Week 20 | Week 32 | Week 44 | Week 56 | Fu Week 4 | Fu Week 24 |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 8.02 | 4.74 | 3.54 | 2.56 | 2.15 | 2.21 | 4.34 | 7.31 |
Percentage of Participants With AEs Leading to Dose Modification or Interruption
This endpoint measures AEs and lab abnormalities leading to dose interruption or dose modification. Does modification included dose reduced, dose increased or drug interrupted. Adverse events included laboratory abnormalities reported as adverse events. (NCT02263079)
Timeframe: Baseline up to 24 weeks post-end of treatment
| Intervention | Percentage of Participants (Number) |
|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | 23.0 |
Change From Baseline to Month 12 in Multiple Sclerosis Functional Composite (MSFC) Score Including the Low-Contrast Letter Acuity (LCLA) Test
"The MSFC-LCLA is a battery including the following 4 individual scales:~Timed 25-Foot Walk is an ambulation measure of walking 25 feet with time taken recorded in seconds~9-Hole Peg Test (9HPT) is a quantitative measure of upper extremity (arm and hand) function~Symbol Digit Modalities Test (SDMT) is a measure of executive cognitive function that assesses processing speed, flexibility, and calculation ability~Low-Contrast Letter Acuity Test (LCLA) used a standardized set of charts to assess low contrast visual acuity, charts are scored according to the number of letters that are identified correctly~Z-scores were calculated for for each component and averaged to create an overall composite score, using the study population as the reference population. A z-score represents the number of standard deviations a patient's test result is higher (z > 0) or lower (z < 0) than the average test result (z = 0) of the reference population. A positive change indicates improvement." (NCT02294058)
Timeframe: Baseline to Month 12
| Intervention | z-score (Mean) |
|---|
| Interferon Beta-1a | -0.022 |
| Ozanimod 0.5 mg | -0.007 |
| Ozanimod 1 mg | 0.003 |
Adjusted Mean Number of New or Enlarging Hyperintense T2-Weighted Brain Magnetic Resonance Imaging (MRI) Lesions Per Scan Over 12 Months
The number of new or enlarging hyperintense T2-weighted brain MRI lesions per scan was based on the cumulative number of new or enlarging T2 lesions since Baseline over treatment period. (NCT02294058)
Timeframe: 12 month treatment period; MRI scans were assessed at Month 6 and Month 12
| Intervention | T2 lesions/scan (Least Squares Mean) |
|---|
| Interferon Beta-1a | 2.836 |
| Ozanimod 0.5 mg | 2.139 |
| Ozanimod 1 mg | 1.465 |
Adjusted Mean Number of Gadolinium Enhancing (GdE) Brain MRI Lesions at Month 12
(NCT02294058)
Timeframe: Month 12
| Intervention | lesions (Least Squares Mean) |
|---|
| Interferon Beta-1a | 0.433 |
| Ozanimod 0.5 mg | 0.287 |
| Ozanimod 1 mg | 0.160 |
Adjusted Annualized Relapse Rate (ARR) During the Treatment Period
"The relapse rate was based on confirmed relapses. A relapse was defined as new or worsening neurological symptoms attributable to MS and preceded by a relatively stable or improving neurological state for at least 30 days. Symptoms must have persisted for > 24 hours and not be attributable to confounding clinical factors. Relapses were confirmed when accompanied by objective neurological worsening based on examination by the blinded evaluator, consistent with an increase of ≥ 0.5 on the overall EDSS score relative to the most recent EDSS assessment, or 2 points on one of the functional system scale scores, or 1 point on ≥ two functional system scale scores.~Relapse rate was calculated as the total number of relapses divided by the total number of days in the study * 365.25.~ARR was adjusted for region (Eastern Europe vs rest of world), Baseline age, and Baseline number of gadolinium-enhancing lesions; the natural log transformation of time on study was included as an offset term." (NCT02294058)
Timeframe: 12 months
| Intervention | relapses/year (Least Squares Mean) |
|---|
| Interferon Beta-1a | 0.350 |
| Ozanimod 0.5 mg | 0.241 |
| Ozanimod 1 mg | 0.181 |
Percent Change From Baseline in Normalized Brain Volume at Month 12
Brain volume (a measure of brain atrophy) was analyzed by MRI. (NCT02294058)
Timeframe: Baseline to Month 12
| Intervention | percent change (Median) |
|---|
| Interferon Beta-1a | -0.57 |
| Ozanimod 0.5 mg | -0.50 |
| Ozanimod 1 mg | -0.39 |
Number of Participants With Treatment Emergent Adverse Events
An adverse event (AE) is any untoward medical occurrence that does not necessarily have a causal relationship with the investigational product (IP). An AE can be any unfavorable or unintended sign, including an abnormal laboratory finding, symptom or disease temporally associated with the use of an IP whether or not considered related to the IP. A serious AE (SAE) is any untoward medical occurrence or effect that results in death, is life-threatening, requires hospitalization or prolongation of existing inpatient hospitalization. The investigator assessed the severity of AEs as mild, moderate, or severe. (NCT02294058)
Timeframe: From the first dose of study drug until 28 days following the last dose of study drug; mean exposure to study drug was 13.5 months for interferon beta-1a and 13.6 months for each ozanimod group.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Any Moderate or Severe TEAE | Any Severe TEAE | Any Suspected TEAE | Any Related TEAE | Any Serious TEAE | Any Suspected Serious TEAE | Any Related Serious TEAE | Any TEAE Leading to Stopping of Study Drug | Any TEAE Leading to Study Withdrawal | Any Death | Any Death related to Study Drug |
|---|
| Interferon Beta-1a | 336 | 182 | 10 | 83 | 13 | 11 | 0 | 0 | 16 | 16 | 0 | 0 |
,| Ozanimod 0.5 mg | 259 | 113 | 10 | 76 | 8 | 16 | 0 | 0 | 7 | 7 | 0 | 0 |
,| Ozanimod 1 mg | 268 | 138 | 7 | 91 | 7 | 13 | 3 | 1 | 13 | 13 | 0 | 0 |
Mean Change From Baseline in Multiple Sclerosis Quality of Life (MSQOL)-54 Physical Health Composite Summary and Mental Health Composite Summary Scores
"The MSQOL-54 is a multidimensional health-related QOL measure that combines both generic and MS-specific items into a single instrument. The instrument includes 12 subscales, two summary scores, and two single-item measures.~The two summary scores - physical health and mental health - are derived from a weighted combination of scale scores.~The physical health composite score includes Physical function, Health perceptions, Energy/fatigue, Role limitations - physical, Pain, Sexual function, Social function, and Health distress.~The mental health composite score includes Health distress, Overall quality of life, Emotional well-being, Role limitations - emotional, and Cognitive function.~Each composite summary score has a range from 0 to 100 where higher scores indicate better quality of life. A positive change from Baseline indicates improvement." (NCT02294058)
Timeframe: Baseline to Month 12
| Intervention | units on a scale (Mean) |
|---|
| Physical health composite summary | Mental health composite summary |
|---|
| Interferon Beta-1a | 0.046 | -0.123 |
,| Ozanimod 0.5 mg | 1.414 | 0.283 |
,| Ozanimod 1 mg | 1.925 | 0.260 |
Time to Onset of Disability Progression Confirmed After 6 Months
"EDSS is used to quantify disability and disability progression over time in MS. Based on a neurological examination, 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, and other functions) are scored from 0 (no disability) to 5 or 6 (more severe disability). Ambulation is assessed based on distance the patient is able to walk, whether assistance is required or restrictions are present.~The EDSS score ranges from 0 (normal) to 10 (death due to MS) in 0.5 unit increments.~Disability progression is defined by a sustained worsening in EDSS score of 1.0 point or more confirmed after 6 months. Time to onset of disability progression was calculated from the date of first dose to the date of the first visit at which the 1.0 point increase in EDSS was met using Kaplan-Meier methods. Participants without a sustained disease progression event were censored on the date of their last assessment or last dose of study drug, whichever was later." (NCT02294058)
Timeframe: From first dose to the end of the 12-month treatment period
| Intervention | days (Median) |
|---|
| Interferon Beta-1a | NA |
| Ozanimod 0.5 mg | NA |
| Ozanimod 1 mg | NA |
Time to Onset of Disability Progression Confirmed After 3 Months
"EDSS is used to quantify disability and disability progression over time in MS. Based on a neurological examination, 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, and other functions) are scored from 0 (no disability) to 5 or 6 (more severe disability). Ambulation is assessed based on distance the patient is able to walk, whether assistance is required or restrictions are present.~The EDSS score ranges from 0 (normal) to 10 (death due to MS) in 0.5 unit increments.~Disability progression is defined by a sustained worsening in EDSS score of 1.0 point or more confirmed after 3 months. Time to onset of disability progression was calculated from the date of first dose to the date of the first visit at which the 1.0 point increase in EDSS was met using Kaplan-Meier methods. Participants without a sustained disease progression event were censored on the date of their last assessment or last dose of study drug, whichever was later." (NCT02294058)
Timeframe: From first dose to the end of the 12-month treatment period
| Intervention | days (Median) |
|---|
| Interferon Beta-1a | NA |
| Ozanimod 0.5 mg | NA |
| Ozanimod 1 mg | NA |
Percentage of Participants Who Were T2 Lesion-Free at Month 12
MRI scans were analyzed by blinded centralized reading facility. (NCT02294058)
Timeframe: Month 12
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a | 23.44 |
| Ozanimod 0.5 mg | 26.39 |
| Ozanimod 1 mg | 27.96 |
Percentage of Participants Who Were Gadolinium Enhancing Lesion-Free at Month 12
MRI scans were analyzed by blinded centralized reading facility. (NCT02294058)
Timeframe: Month 12
| Intervention | percentage of participants (Number) |
|---|
| Interferon Beta-1a | 63.17 |
| Ozanimod 0.5 mg | 68.29 |
| Ozanimod 1 mg | 74.05 |
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 5
Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Week 5 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 5
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 269 | 285 | 784 | 241.5 |
,| Central Retinal Thickness at Baseline in Study Eye | 297.5 | 597 | 713 | 1393 |
,| Central Retinal Thickness at Week 5 in Fellow Eye | 276 | 302 | 580 | 206 |
,| Central Retinal Thickness at Week 5 in Study Eye | 374 | 605 | 473 | 1083 |
,| Difference at Week 5 From Baseline in Fellow Eye | 7 | 17 | -204 | -35.5 |
,| Difference at Week 5 From Baseline in Study Eye | 76.5 | 8 | -240 | -310 |
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 52
Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Week 52 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 52
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 269 | 285 | 784 | 241.5 |
,| Central Retinal Thickness at Baseline in Study Eye | 297.5 | 597 | 713 | 1393 |
,| Central Retinal Thickness at Week 52 in Fellow Eye | 270 | 307 | 457 | 197 |
,| Central Retinal Thickness at Week 52 in Study Eye | 302 | 503 | 437 | 1175 |
,| Difference at Week 52 From Baseline in Fellow Eye | 1 | 22 | -327 | -44.5 |
,| Difference at Week 52 From Baseline in Study Eye | 4.5 | -94 | -276 | -218 |
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 8
Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Week 8 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 8
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 269 | 285 | 784 | 241.5 |
,| Central Retinal Thickness at Baseline in Study Eye | 297.5 | 597 | 713 | 1393 |
,| Central Retinal Thickness at Week 8 in Fellow Eye | 276 | 224 | 667 | 220 |
,| Central Retinal Thickness at Week 8 in Study Eye | 353 | 544 | 456 | 1000 |
,| Difference at Week 8 From Baseline in Fellow Eye | 7 | -61 | -117 | -21.5 |
,| Difference at Week 8 From Baseline in Study Eye | 55.5 | -53 | -257 | -393 |
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Day 1
Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Day 1 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 1
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 278 | 319 | 745 | 260 |
,| Central Retinal Thickness at Baseline in Study Eye | 307 | 619 | 702 | 1413 |
,| Central Retinal Thickness at Day 1 in Fellow Eye | 275 | 317 | 703 | 258 |
,| Central Retinal Thickness at Day 1 in Study Eye | 331 | 607 | 605 | 1418 |
,| Difference at Day 1 From Baseline in Fellow Eye | -3 | -2 | -42 | -2 |
,| Difference at Day 1 From Baseline in Study Eye | 24 | -12 | -97 | 5 |
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Day 2
Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Day 2 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 2
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 278 | 319 | 745 | 260 |
,| Central Retinal Thickness at Baseline in Study Eye | 307 | 619 | 702 | 1413 |
,| Central Retinal Thickness at Day 2 in Fellow Eye | 278 | 318 | 682 | 246 |
,| Central Retinal Thickness at Day 2 in Study Eye | 321 | 611 | 624 | 1427 |
,| Difference at Day 2 From Baseline in Fellow Eye | 0 | -1 | -63 | -14 |
,| Difference at Day 2 From Baseline in Study Eye | 14 | -8 | -78 | 14 |
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Day 3
Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Day 3 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 3
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 278 | 319 | 745 | 260 |
,| Central Retinal Thickness at Baseline in Study Eye | 307 | 619 | 702 | 1413 |
,| Central Retinal Thickness at Day 3 in Fellow Eye | 277 | 320 | 656 | 243 |
,| Central Retinal Thickness at Day 3 in Study Eye | 330 | 587 | 607 | 1393 |
,| Difference at Day 3 From Baseline in Fellow Eye | -1 | 1 | -89 | -17 |
,| Difference at Day 3 From Baseline in Study Eye | 23 | -32 | -95 | -20 |
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 2
Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Week 2 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 2
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 278 | 319 | 745 | 260 |
,| Central Retinal Thickness at Baseline in Study Eye | 307 | 619 | 702 | 1413 |
,| Central Retinal Thickness at Week 2 in Fellow Eye | 276 | 317 | 687 | 234 |
,| Central Retinal Thickness at Week 2 in Study Eye | 333 | 530 | 552 | 1233 |
,| Difference at Week 2 From Baseline in Fellow Eye | -2 | -2 | -58 | -26 |
,| Difference at Week 2 From Baseline in Study Eye | 26 | -89 | -150 | -180 |
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 5
Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Week 5 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 5
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 278 | 319 | 745 | 260 |
,| Central Retinal Thickness at Baseline in Study Eye | 307 | 619 | 702 | 1413 |
,| Central Retinal Thickness at Week 5 in Fellow Eye | 282 | 316 | 591 | 243 |
,| Central Retinal Thickness at Week 5 in Study Eye | 385 | 576 | 509 | 1089 |
,| Difference at Week 5 From Baseline in Fellow Eye | 4 | -3 | -154 | -17 |
,| Difference at Week 5 From Baseline in Study Eye | 78 | -43 | -193 | -324 |
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 52
Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Week 52 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 52
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Week 52 in Fellow Eye | 277 | 472 | 233 |
,| Difference at Week 52 From Baseline in Fellow Eye | -1 | -273 | -27 |
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 52
Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Week 52 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 52
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 278 | 319 | 745 | 260 |
,| Central Retinal Thickness at Baseline in Study Eye | 307 | 619 | 702 | 1413 |
,| Central Retinal Thickness at Week 52 in Study Eye | 309 | 497 | 445 | 1221 |
,| Difference at Week 52 From Baseline in Study Eye | 2 | -122 | -257 | -192 |
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Day 2
Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Day 2 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 2
| Intervention | mm^3 (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Difference at Day 2 From Baseline in Fellow Eye | -0.1 | -0.3 | -3 | -0.2 |
,| Difference at Day 2 From Baseline in Study Eye | -0.15 | -0.05 | -0.95 | 1 |
,| Subretinal Fluid Volume at Baseline in Fellow Eye | 7.1 | 11.2 | 18.55 | 9.25 |
,| Subretinal Fluid Volume at Baseline in Study Eye | 7.25 | 14.15 | 16.1 | 36.3 |
,| Subretinal Fluid Volume at Day 2 in Fellow Eye | 7 | 10.9 | 15.55 | 9.05 |
,| Subretinal Fluid Volume at Day 2 in Study Eye | 7.1 | 14.1 | 15.15 | 37.3 |
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 2
Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Week 2 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 2
| Intervention | mm^3 (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Difference at Week 2 From Baseline in Fellow Eye | 0.2 | -0.2 | -1.55 | -0.25 |
,| Difference at Week 2 From Baseline in Study Eye | 0.35 | -1.05 | -1.8 | -3.8 |
,| Subretinal Fluid Volume at Baseline in Fellow Eye | 7.1 | 11.2 | 18.55 | 9.25 |
,| Subretinal Fluid Volume at Baseline in Study Eye | 7.25 | 14.15 | 16.1 | 36.3 |
,| Subretinal Fluid Volume at Week 2 in Fellow Eye | 7.3 | 11 | 17 | 9 |
,| Subretinal Fluid Volume at Week 2 in Study Eye | 7.6 | 13.1 | 14.3 | 32.5 |
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Day 3
Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Day 3 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 3
| Intervention | mm^3 (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Difference at Day 3 From Baseline in Fellow Eye | 0.35 | 0.05 | -1.55 | -0.15 |
,| Difference at Day 3 From Baseline in Study Eye | 0.25 | -0.4 | -0.8 | -1.3 |
,| Subretinal Fluid Volume at Baseline in Fellow Eye | 7.1 | 11.2 | 18.55 | 9.25 |
,| Subretinal Fluid Volume at Baseline in Study Eye | 7.25 | 14.15 | 16.1 | 36.3 |
,| Subretinal Fluid Volume at Day 3 in Fellow Eye | 7.45 | 11.25 | 17 | 9.1 |
,| Subretinal Fluid Volume at Day 3 in Study Eye | 7.5 | 13.75 | 15.3 | 35 |
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 5
Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Week 5 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 5
| Intervention | mm^3 (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Difference at Week 5 From Baseline in Fellow Eye | 0.2 | 0 | -2.85 | -0.15 |
,| Difference at Week 5 From Baseline in Study Eye | 0.15 | -0.25 | -2.1 | -7.2 |
,| Subretinal Fluid Volume at Baseline in Fellow Eye | 7.1 | 11.2 | 18.55 | 9.25 |
,| Subretinal Fluid Volume at Baseline in Study Eye | 7.25 | 14.15 | 16.1 | 36.3 |
,| Subretinal Fluid Volume at Week 5 in Fellow Eye | 7.3 | 11.2 | 15.7 | 9.1 |
,| Subretinal Fluid Volume at Week 5 in Study Eye | 7.4 | 13.9 | 14 | 29.1 |
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 52
Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Week 52 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 52
| Intervention | mm^3 (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Difference at Week 52 From Baseline in Fellow Eye | -0.1 | 0.1 | -4.25 | -0.35 |
,| Difference at Week 52 From Baseline in Study Eye | -0.35 | -1.45 | -2.3 | -4 |
,| Subretinal Fluid Volume at Baseline in Fellow Eye | 7.1 | 11.2 | 18.55 | 9.25 |
,| Subretinal Fluid Volume at Baseline in Study Eye | 7.25 | 14.15 | 16.1 | 36.3 |
,| Subretinal Fluid Volume at Week 52 in Fellow Eye | 7 | 11.3 | 14.3 | 8.9 |
,| Subretinal Fluid Volume at Week 52 in Study Eye | 6.9 | 12.7 | 13.8 | 32.3 |
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Day 3
Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Day 3 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 3
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 269 | 285 | 784 | 241.5 |
,| Central Retinal Thickness at Baseline in Study Eye | 297.5 | 597 | 713 | 1393 |
,| Central Retinal Thickness at Day 3 in Fellow Eye | 274 | 299 | 682.5 | 220 |
,| Central Retinal Thickness at Day 3 in Study Eye | 323 | 587.5 | 621 | 1361.5 |
,| Difference at Day 3 From Baseline in Fellow Eye | 5 | 14 | -101.5 | -21.5 |
,| Difference at Day 3 From Baseline in Study Eye | 25.5 | -9.5 | -92 | -31.5 |
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Day 2
Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Day 2 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 2
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 269 | 285 | 784 | 241.5 |
,| Central Retinal Thickness at Baseline in Study Eye | 297.5 | 597 | 713 | 1393 |
,| Central Retinal Thickness at Day 2 in Fellow Eye | 279 | 304.5 | 700.5 | 220 |
,| Central Retinal Thickness at Day 2 in Study Eye | 309.5 | 605 | 613 | 1392.5 |
,| Difference at Day 2 From Baseline in Fellow Eye | 10 | 19.5 | -83.5 | -21.5 |
,| Difference at Day 2 From Baseline in Study Eye | 12 | 8 | -100 | -0.5 |
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Week 8
Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Week 8 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 8
| Intervention | mm^3 (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Difference at Week 8 From Baseline in Fellow Eye | 0.3 | -0.3 | -1.45 | 0.15 |
,| Difference at Week 8 From Baseline in Study Eye | 0.15 | -0.65 | -2.3 | -8.7 |
,| Subretinal Fluid Volume at Baseline in Fellow Eye | 7.1 | 11.2 | 18.55 | 9.25 |
,| Subretinal Fluid Volume at Baseline in Study Eye | 7.25 | 14.15 | 16.1 | 36.3 |
,| Subretinal Fluid Volume at Week 8 in Fellow Eye | 7.4 | 10.9 | 17.1 | 9.4 |
,| Subretinal Fluid Volume at Week 8 in Study Eye | 7.4 | 13.5 | 13.8 | 27.6 |
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Day 1
Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Day 1 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 1
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 269 | 285 | 784 | 241.5 |
,| Central Retinal Thickness at Baseline in Study Eye | 297.5 | 597 | 713 | 1393 |
,| Central Retinal Thickness at Day 1 in Fellow Eye | 270.5 | 298.5 | 713.5 | 232.5 |
,| Central Retinal Thickness at Day 1 in Study Eye | 314 | 602 | 598 | 1394.5 |
,| Difference at Day 1 From Baseline in Fellow Eye | 1.5 | 13.5 | -70.5 | -9 |
,| Difference at Day 1 From Baseline in Study Eye | 16.5 | 5 | -115 | 1.5 |
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 8
Change in BCVA from baseline as compared to Week 8 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 8
| Intervention | letters read (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| BCVA at Baseline in Fellow Eye | 80 | 61 | 76 | 42 |
,| BCVA at Baseline in Study Eye | 77 | 39 | 69 | 14 |
,| BCVA at Week 8 in Fellow Eye | 80 | 65 | 70 | 47 |
,| BCVA at Week 8 in Study Eye | 74 | 43 | 72 | 24 |
,| Difference in BCVA at Week 8 From Baseline in Fellow Eye | 0 | 4 | -6 | 5 |
,| Difference in BCVA at Week 8 From Baseline in Study Eye | -3 | 4 | 3 | 10 |
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 52
Change in BCVA from baseline as compared to Week 52 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 52
| Intervention | letters read (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| BCVA at Baseline in Fellow Eye | 80 | 61 | 76 | 42 |
,| BCVA at Baseline in Study Eye | 77 | 39 | 69 | 14 |
,| BCVA at Week 52 in Fellow Eye | 78 | 65 | 65 | 44 |
,| BCVA at Week 52 in Study Eye | 79 | 47 | 65 | 20 |
,| Difference in BCVA at Week 52 From Baseline in Fellow Eye | -2 | 4 | -11 | 2 |
,| Difference in BCVA at Week 52 From Baseline in Study Eye | 2 | 8 | -4 | 6 |
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 5
Change in BCVA from baseline as compared to Week 5 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 5
| Intervention | letters read (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| BCVA at Baseline in Fellow Eye | 80 | 61 | 76 | 42 |
,| BCVA at Baseline in Study Eye | 77 | 39 | 69 | 14 |
,| BCVA at Week 5 in Fellow Eye | 82 | 65 | 75 | 45 |
,| BCVA at Week 5 in Study Eye | 71 | 0 | 72 | 26 |
,| Difference in BCVA at Week 5 From Baseline in Fellow Eye | 2 | 4 | -1 | 3 |
,| Difference in BCVA at Week 5 From Baseline in Study Eye | -6 | -39 | 3 | 12 |
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Week 2
Change in BCVA from baseline as compared to Week 2 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 2
| Intervention | letters read (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| BCVA at Baseline in Fellow Eye | 80 | 61 | 76 | 42 |
,| BCVA at Baseline in Study Eye | 77 | 39 | 69 | 14 |
,| BCVA at Week 2 in Fellow Eye | 78 | 66 | 67 | 42 |
,| BCVA at Week 2 in Study Eye | 75 | 0 | 66 | 23 |
,| Difference in BCVA at Week 2 From Baseline in Fellow Eye | -2 | 5 | -9 | 0 |
,| Difference in BCVA at Week 2 From Baseline in Study Eye | -2 | -39 | -3 | 9 |
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Day 3
Change in BCVA from baseline as compared to Day 3 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 3
| Intervention | letters read (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| BCVA at Baseline in Fellow Eye | 80 | 61 | 76 | 42 |
,| BCVA at Baseline in Study Eye | 77 | 39 | 69 | 14 |
,| BCVA at Day 3 in Fellow Eye | 78 | 61 | 73 | 47 |
,| BCVA at Day 3 in Study Eye | 81 | 41 | 74 | 23 |
,| Difference in BCVA at Day 3 From Baseline in Fellow Eye | -2 | 0 | -3 | 5 |
,| Difference in BCVA at Day 3 From Baseline in Study Eye | 4 | 2 | 5 | 9 |
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Day 2
Change in BCVA from baseline as compared to Day 2 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 2
| Intervention | letters read (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| BCVA at Baseline in Fellow Eye | 80 | 61 | 76 | 42 |
,| BCVA at Baseline in Study Eye | 77 | 39 | 69 | 14 |
,| BCVA at Day 2 in Fellow Eye | 81 | 58 | 69 | 45 |
,| BCVA at Day 2 in Study Eye | 75 | 36 | 75 | 21 |
,| Difference in BCVA at Day 2 From Baseline in Fellow Eye | 1 | -3 | -7 | 3 |
,| Difference in BCVA at Day 2 From Baseline in Study Eye | -2 | -3 | 6 | 7 |
Change in Best Corrected Visual Acuity (BCVA) From Baseline as Compared to Day 1
Change in BCVA from baseline as compared to Day 1 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 1
| Intervention | letters read (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| BCVA at Baseline in Fellow Eye | 80 | 61 | 76 | 42 |
,| BCVA at Baseline in Study Eye | 77 | 39 | 69 | 14 |
,| BCVA at Day 1 in Fellow Eye | 79 | 62 | 70 | 44 |
,| BCVA at Day 1 in Study Eye | 76 | 32 | 74 | 18 |
,| Difference in BCVA at Day 1 From Baseline in Fellow Eye | -1 | 1 | -6 | 2 |
,| Difference in BCVA at Day 1 From Baseline in Study Eye | -1 | -7 | 5 | 4 |
Number of Participants Who Withdrew
The number of participants who withdrew early. (NCT02338973)
Timeframe: Study duration, up to 52 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Interferon Gamma-1b | 0 |
Change in Central Retinal Thickness as Measured on Cirrus OCT From Baseline as Compared to Week 2
Change in central retinal thickness as measured on Cirrus OCT from baseline as compared to Week 2 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 2
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 269 | 285 | 784 | 241.5 |
,| Central Retinal Thickness at Baseline in Study Eye | 297.5 | 597 | 713 | 1393 |
,| Central Retinal Thickness at Week 2 in Fellow Eye | 267 | 300 | 700 | 208 |
,| Central Retinal Thickness at Week 2 in Study Eye | 330 | 534 | 517 | 1193 |
,| Difference at Week 2 From Baseline in Fellow Eye | -2 | 15 | -84 | -33.5 |
,| Difference at Week 2 From Baseline in Study Eye | 32.5 | -63 | -196 | -200 |
Change in Central Retinal Thickness as Measured on Spectralis OCT From Baseline as Compared to Week 8
Change in central retinal thickness as measured on Spectralis OCT from baseline as compared to Week 8 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Week 8
| Intervention | μm (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Central Retinal Thickness at Baseline in Fellow Eye | 278 | 319 | 745 | 260 |
,| Central Retinal Thickness at Baseline in Study Eye | 307 | 619 | 702 | 1413 |
,| Central Retinal Thickness at Week 8 in Fellow Eye | 280 | 313 | 657 | 250 |
,| Central Retinal Thickness at Week 8 in Study Eye | 370 | 545 | 486 | 1020 |
,| Difference at Week 8 From Baseline in Fellow Eye | 2 | -6 | -88 | -10 |
,| Difference at Week 8 From Baseline in Study Eye | 63 | -74 | -216 | -393 |
Change in Central Visual Field Sensitivity at Day 2 and Week 5 Compared to Baseline.
Change in central visual field sensitivity as measured by microperimetry testing at Day 2 and Week 5 compared to baseline in both study and fellow eyes. (NCT02338973)
Timeframe: Day 2 and Week 5
| Intervention | dB (Mean) |
|---|
| Day 2 Study Eye | Day 2 Fellow Eye | Week 5 Study Eye | Week 5 Fellow Eye |
|---|
| Interferon Gamma-1b | -0.3 | -1.4 | -1.1 | -1.7 |
Change in Maximum Subretinal Fluid Volume From Baseline as Compared to Day 1
Change in maximum subretinal fluid volume as measured on OCT from baseline as compared to Day 1 by participant in both study and fellow eyes. (NCT02338973)
Timeframe: Day 1
| Intervention | mm^3 (Number) |
|---|
| Participant 001 | Participant 002 | Participant 003 | Participant 004 |
|---|
| Difference at Day 1 From Baseline in Fellow Eye | 0.25 | 0.05 | -1.35 | -0.05 |
,| Difference at Day 1 From Baseline in Study Eye | 0.1 | -0.2 | -0.95 | 1.4 |
,| Subretinal Fluid Volume at Baseline in Fellow Eye | 7.1 | 11.2 | 18.55 | 9.25 |
,| Subretinal Fluid Volume at Baseline in Study Eye | 7.25 | 14.15 | 16.1 | 36.3 |
,| Subretinal Fluid Volume at Day 1 in Study Eye | 7.35 | 13.95 | 15.15 | 37.7 |
,| Subretinal Fluid Volume at Day1 in Fellow Eye | 7.35 | 11.25 | 17.2 | 9.2 |
Change From Baseline in HCV RNA (log10 IU/mL)
(NCT02340962)
Timeframe: Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)
| Intervention | log10 IU/mL (Mean) |
|---|
| Day 4 | Week 1 | Day 10 | Week 2 | Week 3 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Post-Treatment Week 4 | Post-Treatment Week 8 | Post-Treatment Week 12 | Post-Treatment Week 24 |
|---|
| 200 mg TG-2349 | -3.8 | -4.4 | -4.6 | -4.8 | -5.0 | -5.2 | -5.4 | -5.8 | -5.6 | -5.8 | -5.8 | -5.6 | -5.2 | -5.6 |
,| 400 mg TG-2349 | -3.9 | -4.5 | -4.8 | -4.9 | -5.5 | -5.5 | -5.7 | -5.7 | -5.8 | -5.7 | -5.1 | -5.0 | -4.8 | -5.8 |
Proportion of Subjects Achieving Sustained Viral Response at 4, 8, and 24 Weeks After the End of Treatment (SVR4, SVR8, and SVR24)
(NCT02340962)
Timeframe: 4, 8, 24 weeks after the end of treatment (SVR4, 8, 24), after 12-week treatments
| Intervention | Participants (Count of Participants) |
|---|
| SVR4 | SVR8 | SVR24 |
|---|
| 200 mg TG-2349 | 12 | 11 | 11 |
,| 400 mg TG-2349 | 10 | 10 | 10 |
Proportion of Subjects Experiencing Virologic Failure During Treatment and Viral Relapse After the End of Treatment.
(NCT02340962)
Timeframe: Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Virologic failure | On-Treatment failure | Post-Treatment relapse |
|---|
| 200 mg TG-2349 | 1 | 0 | 1 |
,| 400 mg TG-2349 | 2 | 1 | 1 |
Proportion of Subjects With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal Limit of ALT at Final Treatment Visit.
(NCT02340962)
Timeframe: From baseline (day 1) to the final treatment visit (week 12 or week 24)
| Intervention | Participants (Count of Participants) |
|---|
| ALT > ULN at baseline | ALT normalization |
|---|
| 200 mg TG-2349 | 7 | 2 |
,| 400 mg TG-2349 | 7 | 5 |
Proportion of Subjects Achieving Sustained Viral Response at 12 Weeks After the End of Treatment.
Proportion of subjects with HCV RNA< LLOQ (lower limit of quantification), TD (target detected) or TND (target not detected) at 12 weeks after the end of treatment (SVR12) in the Full Analysis Set (FAS) population, which include subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs. (NCT02340962)
Timeframe: 12 weeks after the end of treatment (SVR12), after 12-week treatments
| Intervention | Participants (Count of Participants) |
|---|
| 200 mg TG-2349 | 11 |
| 400 mg TG-2349 | 10 |
Mean Absolute Values in HCV RNA (log10 IU/mL)
(NCT02340962)
Timeframe: Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)
| Intervention | log10 IU/mL (Mean) |
|---|
| Baseline | Day 4 | Week 1 | Day 10 | Week 2 | Week 3 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Post-Treatment Week 4 | Post-Treatment Week 8 | Post-Treatment Week 12 | Post-Treatment Week 24 |
|---|
| 200 mg TG-2349 | 5.8 | 1.9 | 1.4 | 1.2 | 1.0 | 0.7 | 0.5 | 0.4 | 0.0 | 0.2 | 0.0 | 0.0 | 0.2 | 0.5 | 0.1 |
,| 400 mg TG-2349 | 5.9 | 2.0 | 1.4 | 1.1 | 1.0 | 0.4 | 0.4 | 0.1 | 0.1 | 0.0 | 0.1 | 0.8 | 0.9 | 1.0 | 0.0 |
Proportion of Subjects Achieving HCV RNA < LLOQ, TND
(NCT02340962)
Timeframe: Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Baseline | Day 4 | Week 1 | Day 10 | Week 2 | Week 3 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Post-Treatment Week 4 | Post-Treatment Week 8 | Post-Treatment Week 12 | Post-Treatment Week 24 |
|---|
| Group I | 0 | 0 | 1 | 0 | 2 | 4 | 6 | 7 | 11 | 9 | 11 | 12 | 11 | 11 | 10 |
,| Group II | 0 | 0 | 1 | 3 | 4 | 9 | 9 | 10 | 10 | 11 | 10 | 10 | 10 | 9 | 10 |
Proportion of Subjects Achieving HCV RNA < Lower Limit of Quantification, Target Detected or Target Not Detected (< LLOQ, TD or TND)
(NCT02340962)
Timeframe: The whole treatment period, 12 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Baseline | Day 4 | Week 1 | Day 10 | Week 2 | Week 3 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 |
|---|
| 200 mg TG-2349 | 0 | 1 | 3 | 6 | 9 | 11 | 12 | 11 | 11 | 11 | 11 |
,| 400 mg TG-2349 | 0 | 0 | 4 | 8 | 10 | 10 | 11 | 11 | 11 | 11 | 11 |
Number of Children Responding to Treatment
The objective response of study participants was categorized as complete response, partial response, or stable disease. Determination of tumor response or progression is based on the pre-study baseline scan performed closest to time of study entry. The overall response assessment takes into account response in both target and non-target lesion, and the appearance of new lesions. Complete response is defined as the disappearance of all target lesions and non-target lesions, and no new lesions. Partial response is defined as ≥ 65% decrease in the sum of the products of the three perpendicular diameters of all target lesions, and no development of new lesions. Stable disease is defined as neither sufficient decrease in the sum of the products of the three perpendicular diameters of all target lesions to qualify for partial response, nor sufficient increase in a single target lesion to qualify for progressive disease, as well as no new lesions. (NCT02343224)
Timeframe: Month 12
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Partial Response | Stable Disease |
|---|
| PEGINTRON | 0 | 0 | 5 |
Number of Participants Meeting Event Free Survival Criteria
Event free survival is the time to treatment failure from the time of study enrollment to tumor progression, tumor recurrence, death from any cause or occurrence of a second malignant neoplasm. (NCT02343224)
Timeframe: Month 12, Month 24
| Intervention | Participants (Count of Participants) |
|---|
| Month 12 | Month 24 |
|---|
| PEGINTRON | 7 | 7 |
Number of Participants Meeting Overall Survival Criteria
Overall survival is measured as the time from study enrollment to death from any cause. (NCT02343224)
Timeframe: Month 12, Month 24
| Intervention | Participants (Count of Participants) |
|---|
| Month 12 | Month 24 |
|---|
| PEGINTRON | 7 | 7 |
Adverse Event (AE) and Serious Adverse Event (SAE) Incidence
Stage 1 (NCT02359877)
Timeframe: 4 weeks
| Intervention | participants (Number) |
|---|
| Serious) Adverse Events | Other (Not Including Serious) Adverse Events | Elevated erythrocyte sedimentation rate | Leucopenia | Lymphopenia | Monocytopenia | Monocytosis | Neutropenia | Plasmatization of lymphocytes | Trombocytopenia | Vacuolation of cytoplasm of monocytes | Fever | Flu-like syndrome | Elevated ALT | Elevated AST | Elevated gamma glutamil transferrase | Hyperemia of injection site |
|---|
| Avonex | 0 | 3 | 0 | 3 | 0 | 0 | 1 | 3 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
,| BCD-054 - 120 mcg - IM | 0 | 6 | 2 | 3 | 0 | 0 | 2 | 2 | 0 | 0 | 3 | 0 | 6 | 1 | 0 | 0 | 0 |
,| BCD-054 - 120 mcg - SC | 0 | 6 | 1 | 6 | 0 | 0 | 1 | 3 | 1 | 2 | 0 | 0 | 4 | 0 | 0 | 0 | 3 |
,| BCD-054 - 240 mcg - IM | 0 | 3 | 0 | 2 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 |
,| BCD-054 - 240 mcg - SC | 0 | 3 | 0 | 2 | 0 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 3 | 0 | 0 | 0 | 1 |
,| BCD-054 - 360 mcg - IM | 0 | 3 | 0 | 2 | 1 | 0 | 2 | 2 | 0 | 2 | 1 | 1 | 2 | 0 | 0 | 0 | 0 |
,| BCD-054 - 360 mcg - SC | 0 | 6 | 0 | 6 | 4 | 1 | 0 | 6 | 0 | 6 | 0 | 2 | 4 | 2 | 2 | 1 | 4 |
,| BCD-054 - 60 mcg - IM | 0 | 3 | 0 | 2 | 0 | 0 | 2 | 2 | 0 | 1 | 3 | 0 | 1 | 0 | 0 | 0 | 0 |
,| BCD-054 - 60 mcg - SC | 0 | 3 | 0 | 2 | 0 | 0 | 1 | 2 | 0 | 1 | 3 | 0 | 1 | 0 | 0 | 0 | 1 |
,| Rebif | 0 | 6 | 0 | 2 | 0 | 0 | 0 | 5 | 0 | 2 | 0 | 0 | 4 | 0 | 0 | 0 | 1 |
AUC (0-168); AUC (0-336); AUC (0-672); AUC (0-∞ ) of Interferon (IFN) Beta-1a
Stage 1 primary outcome measure for pharmacokinetics analysis. Area under concentration-time curve (AUC) of interferon (IFN) beta-1a from the moment of drug administration up to 168, 336, 648 hours respectively (NCT02359877)
Timeframe: 0 to 168 hours; 0 to 336 hours; 0 to 672 hours respectively
| Intervention | (pg/ml)*hour (Median) |
|---|
| AUC (0-168) | AUC (0-336) | AUC (0-672) | AUC (0-∞ ) |
|---|
| Avonex | 5995 | 6964 | 7544 | 7544 |
,| BCD-054 - 120 mcg - IM | 176866 | 196189 | 196189 | 196189 |
,| BCD-054 - 120 mcg - SC | 279477 | 345510 | 351768 | 351768 |
,| BCD-054 - 240 mcg - IM | 420038 | 437275 | 437275 | 437275 |
,| BCD-054 - 240 mcg - SC | 405395 | 426025 | 426025 | 426025 |
,| BCD-054 - 360 mcg - IM | 376277 | 407273 | 410751 | 410751 |
,| BCD-054 - 360 mcg - SC | 1052951 | 1457973 | 1554173 | 1562327 |
,| BCD-054 - 60 mcg - IM | 87085 | 103624 | 107471 | 107471 |
,| BCD-054 - 60 mcg - SC | 36682 | 44569 | 44569 | 44569 |
,| Rebif | 20423 | 36866 | 53715 | 54774 |
Adverse Event (AE) and Serious Adverse Event (SAE) Incidence BCD-054 - 180 mcg - SC/IM
Stage 2 BCD-054 - 180 mcg - SC/IM (NCT02359877)
Timeframe: 4 weeks
| Intervention | participants (Number) |
|---|
| Serious Adverse Events | Other (Not Including Serious) Adverse Events | Leucopenia | Neutropenia | Trombocytopenia | Flu-like syndrome | Elevated ALT | Elevated AST | Elevated creatinine | Hyperemia of injection site |
|---|
| BCD-054 - 180 mcg - IM | 0 | 6 | 6 | 5 | 3 | 4 | 2 | 2 | 1 | 0 |
,| BCD-054 - 180 mcg - SC | 0 | 8 | 4 | 5 | 1 | 7 | 3 | 3 | 0 | 1 |
AUC(0-last); AUC (0-∞ ) BCD-054 of Interferon (IFN) Beta-1a - 180 mcg - SC, BCD-054 - 180 mcg - IM
Stage 2 primary outcome measure for pharmacokinetics analysis. Area under concentration-time curve (AUC) of interferon (IFN) beta-1a from the moment of drug administration until last quantifiable concentration (NCT02359877)
Timeframe: 0 to 672 hours
| Intervention | (pg/ml)*hour (Median) |
|---|
| AUC(0-last) | AUC (0-∞) |
|---|
| BCD-054 - 180 mcg - IM | 210626 | 218817 |
,| BCD-054 - 180 mcg - SC | 274888 | 316204 |
AUC(0-∞), AUC(0-last) of Neopterin
Stage 2 primary outcome measure for pharmacodynamics analysis. Area under concentration-time curve (AUC) of neopterin from the moment of drug administration until last quantifiable concentration (NCT02359877)
Timeframe: 0 to 672 hours
| Intervention | (nmol/L)*hour (Median) |
|---|
| AUC(0-∞) | AUC(0-last) |
|---|
| BCD-054 - 180 mcg - IM | 3431 | 3242 |
,| BCD-054 - 180 mcg - SC | 3757 | 3303 |
AUC (0-168); AUC (0-336); AUC (0-672);AUC (0-∞ ) of Neopterin
Stage 1 primary outcome measure for pharmacodynamics analysis. Area under concentration-time curve (AUC) of neopterin from the moment of drug administration until 168, 336, 648 hours respectively (NCT02359877)
Timeframe: 0 to 168 hours; 0 to 336 hours; 0 to 672 hours respectively
| Intervention | nmol/L*hour (Median) |
|---|
| AUC (0-168) | AUC (0-336) | AUC (0-672) | AUC (0-∞ ) |
|---|
| Avonex | 5995 | 6964 | 7544 | 7544 |
,| BCD-054 - 120 mcg - IM | 176865 | 196189 | 196189 | 196189 |
,| BCD-054 - 120 mcg - SC | 279477 | 345509 | 351767 | 351767 |
,| BCD-054 - 240 mcg - IM | 420038 | 437275 | 437275 | 437275 |
,| BCD-054 - 240 mcg - SC | 405394 | 426024 | 426024 | 426024 |
,| BCD-054 - 360 mcg - IM | 376277 | 407273 | 410750 | 410750 |
,| BCD-054 - 360 mcg - SC | 1052951 | 1457972 | 1554173 | 1562327 |
,| BCD-054 - 60 mcg - IM | 87084 | 103624 | 107471 | 107471 |
,| BCD-054 - 60 mcg - SC | 36681 | 44569 | 44569 | 44569 |
,| Rebif | 20423 | 36865 | 53714 | 54774 |
Change From Baseline to Week 26 in Total Friedreich Ataxia Rating Scale Score (FARStot)
The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions are assessed. FARStot scores range from 0 (normal) to 125 (most impairment). A negative change from baseline indicates improvement. (NCT02415127)
Timeframe: Baseline, Week 26
| Intervention | units on a scale (Mean) |
|---|
| Interferon γ-1b | -0.2 |
| Placebo | -0.6 |
Change From Baseline to Week 26 in the Friedreich's Ataxia Rating Scale (FARS)-mNeuro Score
The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions were assessed. The FARS-mNeuro score excludes the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score. Scores range from 0 (normal) to 93 (most impairment). A negative change from baseline is an improvement. (NCT02415127)
Timeframe: Baseline, Week 26
| Intervention | units on a scale (Mean) |
|---|
| Interferon γ-1b | -0.6 |
| Placebo | -1.0 |
Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score
Participants and/or their caregivers rated 9 areas of daily living skills (speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function) on a 5-point scale (0=normal, 4=greatest loss of function) with allowable increments of 0.5 if the participant or caregiver strongly felt that a task falls between 2 scores. ADL scores can range from 0 (normal) to 36 (greatest loss of function). A negative change from baseline indicates improvement. (NCT02415127)
Timeframe: Baseline, Week 26
| Intervention | units on a scale (Mean) |
|---|
| Interferon γ-1b | 0.64 |
| Placebo | 0.01 |
Improvement in Quantitative Serum HDV RNA Levels After 4-12 Weeks of Lonafarnib-based Therapy
log HDV RNA decline from baseline to end of treatment (4-12 weeks of lonafarnib-based therapy) (NCT02430181)
Timeframe: 4-12 weeks
| Intervention | log IU/mL (Mean) |
|---|
| Lonafarnib 200 mg BID | 0.03 |
| Lonafarnib 300 mg BID | -1.78 |
| Lonafarnib 100 mg TID | -1.3 |
| 100 mg BID Lonafarnib/PEG IFN-a | -1.85 |
| 200 mg BID Lonafarnib/PEG IFN-a | 0 |
| 300 mg BID Lonafarnib/PEG IFN-a | 0 |
| Lonafarnib/Ritonavir | -1.2 |
ALT Normalization at End of Treatment
Proportion of intent to treat population who normalize ALT at end of treatment (NCT02430194)
Timeframe: 12-48 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Lonafarnib/Ritonavir - I | 3 |
| Lonafarnib/Ritonavir - II | 1 |
| Lonafarnib/Ritonavir - III | 1 |
| Lonafarnib/Ritonavir - IV | 2 |
| Lonafarnib/Ritonavir - V | 0 |
| Lonafarnib/Ritonavir - VI | 2 |
| Lonafarnib/Ritonavir - VII | 6 |
| Lonafarnib/Ritonavir/PEG IFN-a - VIII | 0 |
| Lonafarnib/Ritonavir/PEG IFN-a - IX | 5 |
| Lonafarnib/Ritonavir/PEG IFN-a - X | 2 |
< LLOQ in HDV RNA at End of Treatment (EOT)
Proportion of intent to treat patients with HDV RNA below the limit of quantitation at end of treatment (NCT02430194)
Timeframe: 12-48 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Lonafarnib/Ritonavir - I | 0 |
| Lonafarnib/Ritonavir - II | 1 |
| Lonafarnib/Ritonavir - III | 1 |
| Lonafarnib/Ritonavir - IV | 0 |
| Lonafarnib/Ritonavir/PEG IFN-a - V | 1 |
| Lonafarnib/Ritonavir - VI | 0 |
| Lonafarnib/Ritonavir - VII | 6 |
| Lonafarnib/Ritonavir/PEG IFN-a - VIII | 1 |
| Lonafarnib/Ritonavir/PEG IFN-a - IX | 3 |
| Lonafarnib/Ritonavir/PEG IFN-a - X | 2 |
≥2 log10 Decline of HDV RNA From Baseline at End of Treatment (EOT)
Proportion of intent to treat patients with ≥2 log10 decline of HDV RNA from baseline at end of treatment (EOT) (NCT02430194)
Timeframe: 12-48 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Lonafarnib/Ritonavir - I | 1 |
| Lonafarnib/Ritonavir - II | 0 |
| Lonafarnib/Ritonavir - III | 1 |
| Lonafarnib/Ritonavir - IV | 0 |
| Lonafarnib/Ritonavir/PEG IFN-a - V | 1 |
| Lonafarnib/Ritonavir - VI | 1 |
| Lonafarnib/Ritonavir - VII | 5 |
| Lonafarnib/Ritonavir/PEG IFN-a - VIII | 4 |
| Lonafarnib/Ritonavir/PEG IFN-a - IX | 3 |
| Lonafarnib/Ritonavir/PEG IFN-a - X | 4 |
Mean HDV RNA Decline
mean HDV RNA decline of intent to treat population from baseline to end of treatment (NCT02430194)
Timeframe: 12-48 weeks
| Intervention | log HDV RNA IU/mL (Mean) |
|---|
| Lonafarnib/Ritonavir - I | -1.39 |
| Lonafarnib/Ritonavir - II | 0.33 |
| Lonafarnib/Ritonavir - III | -1.11 |
| Lonafarnib/Ritonavir - IV | -0.67 |
| Lonafarnib/Ritonavir/PEG IFN-a - V | -1.97 |
| Lonafarnib/Ritonavir - VI | -0.31 |
| Lonafarnib/Ritonavir - VII | -1.94 |
| Lonafarnib/Ritonavir/PEG IFN-a - VIII | -2.85 |
| Lonafarnib/Ritonavir/PEG IFN-a - IX | -2.69 |
| Lonafarnib/Ritonavir/PEG IFN-a - X | -3.81 |
AUC for Change in the Evening PEF From Baseline to up to 30 Days
"Patients measured evening PEF at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation.~The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30." (NCT02491684)
Timeframe: From baseline up to 30 days after start of treatment phase.
| Intervention | l/min (Least Squares Mean) |
|---|
| Days 1-14 | Days 1-7 | Days 8-14 | Days 15-30 |
|---|
| AZD9412 | 10.96 | 8.78 | 8.49 | 11.88 |
,| Placebo | -0.73 | -2.41 | -2.66 | -5.25 |
Proportion of Patients With Severe Asthma Exacerbations Within 7 and 30 Days Following Randomisation
"Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing severe exacerbations within 7 and 30 days after the start of treatment (Day 1).~A severe exacerbation was defined as worsening asthma symptoms and~use of systemic corticosteroids (or a temporary increase of at least 2-fold in a stable oral corticosteroid background dose) for at least 3 consecutive days and/or~an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or~an in-patient hospitalisation due to asthma requiring at least 1 dose of systemic corticosteroids.~The numbers of patients with severe asthma exacerbations with onset during Days 1 - 7 and Days 1 - 30 are presented for each treatment group." (NCT02491684)
Timeframe: Day 1 of treatment phase up to 30 days post-randomisation.
| Intervention | Participants (Count of Participants) |
|---|
| Days 1 - 7 | Days 1 - 30 |
|---|
| AZD9412 | 4 | 8 |
,| Placebo | 2 | 6 |
Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation
"Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing moderate exacerbations within 7, 14 and 30 days after the start of treatment (Day 1).~A moderate exacerbation was defined as a temporary increase in maintenance therapy in order to prevent a severe event supported by a sustained (2 or more days) worsening in at least one key control metric, including asthma score, rescue use, night time awakening or morning peak expiratory flow.~The numbers of patients with moderate exacerbations with onset during Days 1 - 7, Days 1 - 14 and Days 1 - 30 are presented for each treatment group.~With respect to the Day 1-7 analysis, the model did not converge so the analysis could not be performed." (NCT02491684)
Timeframe: Day 1 of treatment phase up to 30 days post-randomisation.
| Intervention | Participants (Count of Participants) |
|---|
| Days 1 - 7 | Days 1 - 14 | Days 1 - 30 |
|---|
| AZD9412 | 0 | 1 | 1 |
,| Placebo | 1 | 1 | 1 |
AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days
"Patients measured morning FEV1 at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation.~The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30." (NCT02491684)
Timeframe: From baseline up to 30 days after start of treatment phase.
| Intervention | litres (Least Squares Mean) |
|---|
| Days 1-14 | Days 1-7 | Days 8-14 | Days 15-30 |
|---|
| AZD9412 | -0.00 | 0.10 | -0.03 | 0.15 |
,| Placebo | -0.08 | 0.02 | -0.09 | 0.04 |
AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days
"Patients measured morning PEF at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation.~The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30." (NCT02491684)
Timeframe: From baseline up to 30 days after start of treatment phase.
| Intervention | litres/minute (l/min) (Least Squares Mean) |
|---|
| Days 1-14 | Days 1-7 | Days 8-14 | Days 15-30 |
|---|
| AZD9412 | 9.56 | 19.66 | 7.03 | 32.75 |
,| Placebo | -7.42 | 0.31 | -7.35 | 13.49 |
Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6)
"The ACQ-6 consists of 6 questions to assess asthma control, each question measured on a 7-point scale scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 total score is computed as the un-weighted mean of the responses to the 6 questions. Baseline assessments were taken as the last non-missing assessment prior to randomisation.~The change from baseline at Visit 4 (Day 7 +/- 1), at Visit 6 (Day 14 +/- 1) and at Visit 8 (Day 30) is presented for the total score and for each of the 6 questions." (NCT02491684)
Timeframe: From baseline up to 30 days after start of treatment phase.
| Intervention | Units on a Scale (Least Squares Mean) |
|---|
| ACQ-6 Total Score, Visit 4 | ACQ-6 Total Score, Visit 6 | ACQ-6 Total Score, Visit 8 | Q1: Woken by Asthma, Visit 4 | Q1: Woken by Asthma, Visit 6 | Q1: Woken by Asthma, Visit 8 | Q2: Symptoms at Awakening, Visit 4 | Q2: Symptoms at Awakening, Visit 6 | Q2: Symptoms at Awakening, Visit 8 | Q3: Limited in Activities, Visit 4 | Q3: Limited in Activities, Visit 6 | Q3: Limited in Activities, Visit 8 | Q4: Shortness of Breath, Visit 4 | Q4: Shortness of Breath, Visit 6 | Q4: Shortness of Breath, Visit 8 | Q5: Wheeze, Visit 4 | Q5: Wheeze, Visit 6 | Q5: Wheeze, Visit 8 | Q6: Puffs of Short-Acting Bronchodilator; Visit 4 | Q6: Puffs of Short-Acting Bronchodilator; Visit 6 | Q6: Puffs of Short-Acting Bronchodilator; Visit 8 |
|---|
| AZD9412 | 0.02 | -0.15 | -0.42 | 0.09 | 0.15 | -0.50 | 0.06 | -0.40 | -0.76 | 0.04 | -0.12 | -0.43 | -0.13 | -0.34 | -0.46 | 0.13 | -0.17 | -0.33 | 0.06 | 0.07 | 0.04 |
,| Placebo | -0.07 | -0.21 | -0.35 | -0.09 | -0.28 | -0.32 | -0.17 | -0.33 | -0.47 | 0.06 | 0.16 | -0.33 | -0.11 | -0.38 | -0.37 | 0.08 | -0.17 | -0.42 | 0.00 | -0.11 | -0.03 |
Change in the Proportion of Night-time Awakening Using the ePRO Questionnaire From Baseline up to 30 Days
"Night-time awakenings due to asthma symptoms were recorded by the patient in the Asthma Daily Diary each morning by answering the question whether he/she woke up during the night due to asthma symptoms with a 'yes' or 'no' response.~Biweekly means were calculated as the percentages of times the subject answered 'yes' over a period of 14 sequential days. Biweekly means are presented for the periods over Days 2-15 and Days 16-30." (NCT02491684)
Timeframe: From baseline up to 30 days after start of treatment phase.
| Intervention | Percentage of 'yes' responses (Mean) |
|---|
| Days 2-15 | Days 16-30 |
|---|
| AZD9412 | 22.3 | 15.2 |
,| Placebo | 24.8 | 15.9 |
AUC for Change in Daytime and Night-time Reliever Medication Use From Baseline up to 14 Days
"Patients recorded the number of reliever medication inhalations taken twice daily in the Asthma Daily Diary. The number of inhalations taken between the morning and evening lung function assessments were recorded in the evening. The number of inhalations taken between the evening and morning lung function assessments were recorded in the morning. Baseline assessments were taken as the last non-missing assessment prior to randomisation.~The AUC for change from baseline over Days 1-14 (inclusive of Days 1 and 14) is presented." (NCT02491684)
Timeframe: From baseline up to Day 14 of treatment phase.
| Intervention | Inhalations (Least Squares Mean) |
|---|
| AZD9412 | -0.12 |
| Placebo | -0.67 |
Duration of Moderate or Severe Exacerbations
"The duration of each individual moderate or severe exacerbation was calculated as:~Cessation date of exacerbation - Start date of exacerbation + 1.~The start date of a severe exacerbation was defined as the start date of systemic corticosteroids or increase of systemic corticosteroids or emergency room visit or hospital admission, whichever occurred first. The stop date was defined as the last day of systemic corticosteroids/increase of systemic corticosteroids or hospital discharge, whichever occurred last.~The start date of a moderate exacerbation was defined as the first day of increase in temporary maintenance therapy. The stop date was defined as the last day of this treatment.~The mean duration of moderate or severe exacerbations is presented for each treatment group." (NCT02491684)
Timeframe: Day 1 of treatment phase up to 30 days post-randomisation.
| Intervention | Days (Mean) |
|---|
| AZD9412 | 10 |
| Placebo | 8 |
AUC for Change in the Evening FEV1 From Baseline up to 30 Days
"Patients measured evening FEV1 at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation.~The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30." (NCT02491684)
Timeframe: From baseline up to 30 days after start of treatment phase.
| Intervention | litres (Least Squares Mean) |
|---|
| Days 1-14 | Days 1-7 | Days 8-14 | Days 15-30 |
|---|
| AZD9412 | -0.01 | 0.01 | -0.02 | 0.02 |
,| Placebo | -0.07 | -0.03 | -0.08 | -0.08 |
Proportion of Patients With a Severe Asthma Exacerbation During 14 Days of Treatment
"Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing severe exacerbations during the 14 day treatment phase following the onset of an URTI in asthmatic patients.~A severe exacerbation was defined as worsening asthma symptoms and~use of systemic corticosteroids (or a temporary increase of at least 2-fold in a stable oral corticosteroid background dose) for at least 3 consecutive days and/or~an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or~an in-patient hospitalisation due to asthma requiring at least 1 dose of systemic corticosteroids.~The number of patients with severe asthma exacerbations with onset during the treatment phase is presented for each treatment group." (NCT02491684)
Timeframe: Day 1 - 14 of the treatment phase.
| Intervention | Participants (Count of Participants) |
|---|
| AZD9412 | 7 |
| Placebo | 5 |
Time to First Moderate Asthma Exacerbation During 30 Days Following Randomisation
"The time to first event was calculated as start date of events - date of randomisation + 1.~Patients with no observed event were censored at the date of their last visit, or for lost-to-follow-up patients, at the last time point after which an event could not be assessed.~The median time to first exacerbation was not calculated in either treatment group due to low numbers of events." (NCT02491684)
Timeframe: From Day 1 of treatment phase up to 30 days post-randomisation.
| Intervention | Days (Median) |
|---|
| AZD9412 | NA |
| Placebo | NA |
Time to First Severe Asthma Exacerbation During 30 Days Following Randomisation
"The time to first event was calculated as start date of events - date of randomisation + 1.~Patients with no observed event were censored at the date of their last visit, or for lost-to-follow-up patients, at the last time point after which an event could not be assessed.~The median time to first exacerbation was not calculated in either treatment group due to low numbers of events." (NCT02491684)
Timeframe: From Day 1 of treatment phase up to 30 days post-randomisation.
| Intervention | Days (Median) |
|---|
| AZD9412 | NA |
| Placebo | NA |
AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days
Asthma symptoms during night-time and daytime were recorded by the patient each morning and evening in the Asthma Daily Diary on a daily basis. Symptoms were recorded using a scale of 0 to 3 where 0 indicates no asthma symptoms up to an absolute score of 3. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The total daily asthma symptom score was calculated by taking the sum of the night-time and daytime asthma scores recorded each day. The outcome variable is the area under the curve (AUC) for change from baseline in day-time, night-time and total daily asthma symptom scores over Days 1-14, Days 1-7, Days 8-14 and Days 15-30. (NCT02491684)
Timeframe: From baseline up to 30 days after start of treatment phase.
| Intervention | Units on Scale (Least Squares Mean) |
|---|
| Total asthma score, Days 1-14 | Total asthma score, Days 1-7 | Total asthma score, Days 8-14 | Total asthma score, Days 15-30 | Daytime asthma score, Days 1-14 | Daytime asthma score, Days 1-7 | Daytime asthma score, Days 8-14 | Daytime asthma score, Days 15-30 | Night-time asthma score, Days 1-14 | Night-time asthma score, Days 1-7 | Night-time asthma score, Days 8-14 | Night-time asthma score, Days 15-30 |
|---|
| AZD9412 | -0.20 | -0.11 | -0.40 | -0.77 | -0.22 | -0.17 | -0.23 | -0.44 | -0.17 | -0.10 | -0.20 | -0.44 |
,| Placebo | -0.31 | -0.22 | -0.41 | -0.77 | -0.26 | -0.17 | -0.27 | -0.41 | -0.16 | -0.09 | -0.17 | -0.39 |
Change in Insulin Resistance
Change in insulin resistance while on treatment by the homeostasis model assessment - insulin resistance (HOMA-IR). HOMA-IR is calculated according to the formula (fasting insulin (microU/L)+fasting glucose (nmol/L)/22.5. Fasting insulin and glucose measurements are obtained using whole blood. (NCT02541409)
Timeframe: Difference from entry to 24 weeks for SOF+PEG+RBV and difference from entry to 36 weeks for SOF+RBV
| Intervention | HOMA-IR (Median) |
|---|
| SOF+PEG+RBV | 1.2 |
| SOF+RBV | 0.2 |
HCV Treatment Completion
The percentage of subjects that complete their course of treatment (NCT02541409)
Timeframe: 12 weeks from baseline for SOF+PEG+RBV and 24 weeks from baselne for SOF+RBV
| Intervention | Participants (Count of Participants) |
|---|
| SOF+PEG+RBV | 22 |
| SOF+RBV | 22 |
Serious Adverse Events
Number of participants with treatment-related serious adverse events by laboratory tests and physician examination (NCT02541409)
Timeframe: 24 weeks from baseline SOF+PEG+RBV and 36 weeks from baseline for SOF+RBV
| Intervention | Participants (Count of Participants) |
|---|
| SOF+PEG+RBV | 0 |
| SOF+RBV | 0 |
Sustained Virologic Response (SVR)
The percentage of participants who achieve SVR as assessed by undetectable HCV RNA measured 12 weeks after treatment completion (NCT02541409)
Timeframe: 24 weeks from baseline for SOF+PEG+RBV and 36 weeks from baseline for SOF+RBV
| Intervention | Participants (Count of Participants) |
|---|
| SOF+PEG+RBV | 22 |
| SOF+RBV | 15 |
Count of Participants Who Displayed Persistence of Transferred T Cells in Blood and Tumor (Group Co2)
Persistence of trasferred T cells was evaluated and assessed after 90 days. Patients were counted if transferred T cells were detected beyond 90 days. (NCT02584829)
Timeframe: Up to 90 days post infusion
| Intervention | Participants (Count of Participants) |
|---|
| Group 2 (Avelumab, MHC Class I Up-regulation, T Cells) | 4 |
Count of Participants That Displayed Evidence of Epitope Spreading
Quantification of the overall recognition of the MCPyV T-antigen for each patient will likely be performed by testing the reactivity of whole peripheral blood mononuclear cells (PBMC) before and at indicated timepoints after treatment to peptides 15 amino acids (aa) in length offset by 5 aa bases spanning the whole T-antigen protein to include both CD8 and CD4 responses regardless of the HLA type of the patient. Due to changes in assay technology, epitope spreading was detected using a flow cytometric based intracellular cytokine assay. (NCT02584829)
Timeframe: Up to 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Group 2 (Avelumab, MHC Class I Up-regulation, T Cells) | 2 |
Count of Participants Who Experienced Adverse Events, Evaluated According to the Current Guidelines in National Cancer Institute (NCI) Common Toxicity Criteria Version 4.0
Evidence and nature of toxicity related to the treatment will be assessed and compared between groups. (NCT02584829)
Timeframe: Up to 4 weeks after the last infusion
| Intervention | Participants (Count of Participants) |
|---|
| Group 1 (Avelumab and MHC Class I Up-regulation) | 1 |
| Group 2 (Avelumab, MHC Class I Up-regulation, T Cells) | 6 |
Functional Capacity of Transferred T Cells (Group 2)
To evaluate the direct ex vivo function of the transferred cells, where possible, tetramer+ cells within collected peripheral blood mononuclear cells (PBMCs) will be evaluated for production of intracellular cytokines including interferon (IFN), tumor necrosis factor alpha and interleukin-2 in response to cognate antigen using an intracellular cytokine assay. This endpoint was evaluable in 4 of 7 patients, all 4 of whom upregulated interferon, tumor necrosis factor alpha and IL-2 expression in response to cognate antigen using intracellular cytokine assay. Persistence was not detected for 3 out of 7 patients in group 2, making them unevaluable for functional capacity. (NCT02584829)
Timeframe: Up to 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Group 2 (Avelumab, MHC Class I Up-regulation, T Cells) | 4 |
Merkel Cell Carcinoma (MCC)-Specific Survival
Survival status in patients with Merkel cell carcinoma will be evaluated. Data is reported as count of participants that survived past the 1 year follow up period. (NCT02584829)
Timeframe: Up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Group 1 (Avelumab and MHC Class I Up-regulation) | 1 |
| Group 2 (Avelumab, MHC Class I Up-regulation, T Cells) | 6 |
Number of Participants With Clinical Abnormal Laboratory Values
Participants with clinical abnormal laboratory values were reported throughout the studies. (NCT02587065)
Timeframe: Baseline up to Week 24
| Intervention | Participants (Count of Participants) |
|---|
| Baseline | Week 12 | Week 24 |
|---|
| Peg-interferon Beta-1a 125 μg | 4 | 3 | 3 |
Change From Baseline in Number of Participants With Adherence to Study Treatment at Weeks 12 and 24
Adherence to treatment was evaluated using a questionnaire assessing adherence and the reasons for not taking drug at the recommended frequency of administration. Participants who had taken the prescribed doses of treatment in the previous 28 days were evaluated. (NCT02587065)
Timeframe: Baseline, Weeks 12 and 24
| Intervention | participants (Number) |
|---|
| Baseline | Change at Week 12 | Change at Week 24 |
|---|
| Peg-interferon Beta-1a 125 μg | 113 | 65 | 53 |
Change From Baseline in Multiple Sclerosis International Quality of Life Questionnaire (MusiQoL) Score at Week 12 and 24
MusiQoL is a self-administered questionnaire consisting of 31 items describing nine dimensions of health-related quality of life (QoL): activities of daily living, psychological wellbeing, symptoms, relationship with friends, relationship with family, sentimental and sexual life, coping rejection, relationship with healthcare system). All items are scored based on frequency/extent of an event on a five-point scale ranging from never/not at all (option 1) to always/very much (option 5). Total score is obtained by linearly transforming and standardizing on a 0-100 scale. Higher scores indicate a better level of health-related QoL for each dimension and for the global index score. Here, negative values indicate improvement in MusiQoL score from baseline. (NCT02587065)
Timeframe: Baseline, Weeks 12 and 24
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Change at Week 12 | Change at Week 24 |
|---|
| Peg-interferon Beta-1a 125 μg | 67.8 | 4.6 | 5.0 |
Change From Baseline in Fatigue Status Scale (FSS) Score at Weeks 12 and 24
FSS is a questionnaire composed of nine statements on the state of fatigue experienced during the previous week. The answers are within a scale of agreement ranging from 1 to 7, where 1 represents less fatigue and 7 indicates highest fatigue. The total score was obtained summing the number given at each item and it ranges from 7 to 63. An overall score of ≥36 indicates a state of fatigue. Questionnaires were completed electronically by participants, by means of a participant i-PAD at each study visit. Here, negative values indicate improvement in FSS score from baseline. (NCT02587065)
Timeframe: Baseline, Weeks 12 and 24
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Change at Week 12 | Change at Week 24 |
|---|
| Peg-interferon Beta-1a 125 μg | 40.1 | -4.6 | -3.8 |
Number of Participants With AE Stratified by Severity
Severity of AEs was evaluated based on the following criteria- Mild: Symptoms barely noticeable to participant or does not make participant uncomfortable; does not influence performance or functioning; prescription drug not ordinarily needed for relief of symptom(s) but may be given because of personality of participant. Moderate: Symptoms of a sufficient severity to make participant uncomfortable; performance of daily activity is influenced; participant is able to continue in study; treatment for symptom(s) may be needed. Severe: Symptoms cause severe discomfort; symptoms cause incapacitation or significant impact on participant's daily life; severity may cause cessation of treatment with study treatment; treatment for symptom(s) may be given and/or participant hospitalized. (NCT02587065)
Timeframe: Baseline up to Week 24
| Intervention | Participants (Count of Participants) |
|---|
| Mild | Moderate |
|---|
| Peg-interferon Beta-1a 125 μg | 55 | 27 |
Change From Baseline in Convenience Satisfaction Score of Treatment Satisfaction Questionnaire to Medication (TSQM-9) at Week 12
TSQM is a 14-item instrument consisting of four scales: effectiveness scale (questions 1 to 3), side effects scale (questions 4 to 8), convenience scale (questions 9 to 11) and global satisfaction scale (questions 12 to 14). In TSQM-9, the five items related to side effects of medication were not included. The scores were computed by adding items for each domain. The lowest possible score was subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that was then multiplied by 100. TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain. Questionnaires were completed electronically by participants, by means of a participant i-PAD at each study visit. (NCT02587065)
Timeframe: Baseline, Week 12
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Change at Week 12 |
|---|
| Peg-interferon Beta-1a 125 μg | 38.5 | 38.5 |
Change From Baseline in Annualized Relapse Rate (ARR) at Week 24
Relapses are defined as neurologic symptoms lasting more than 24 hours which occur at least 30 days after the onset of a preceding event. ARR was calculated as the total number of relapses for all participants divided by the total participant-years of exposure to that treatment. Here negative sign indicates decrease in annual relapse rate as compared to baseline. (NCT02587065)
Timeframe: Baseline, Week 24
| Intervention | relapses per participant-year (Number) |
|---|
| Baseline | Change at Week 24 |
|---|
| Peg-interferon Beta-1a 125 μg | 0.15 | -0.03 |
Percent Change in Relapse-Free Participants at Week 24
Relapses are defined as neurologic symptoms lasting more than 24 hours which occur at least 30 days after the onset of a preceding event. Percent change in relapse-free participants had been calculated with respect to the number of relapse-free participants at baseline. Here, negative sign indicates decrease in number of relapse free participants at specified timepoint as compared to baseline. (NCT02587065)
Timeframe: Baseline, Week 24
| Intervention | percentage change (Number) |
|---|
| Peg-interferon Beta-1a 125 μg | -7.94 |
Change From Baseline in the Score of All Domains of TSQM-9 at Week 24
TSQM is a 14-item instrument consisting of four scales: effectiveness scale (questions 1 to 3), side effects scale (questions 4 to 8), convenience scale (questions 9 to 11) and global satisfaction scale (questions 12 to 14). In TSQM-9, the five items related to side effects of medication were not included. The scores were computed by adding items for each domain. The lowest possible score was subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that was then multiplied by 100. TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain. Questionnaires were completed electronically by participants, by means of a participant i-PAD at each study visit. (NCT02587065)
Timeframe: Baseline, Week 24
| Intervention | score on a scale (Mean) |
|---|
| Baseline: Convenience Satisfaction | Change at Week 24: Convenience Satisfaction | Baseline: Effectiveness | Change at Week 24: Effectiveness | Baseline: Global satisfaction | Change at Week 24: Global satisfaction |
|---|
| Peg-interferon Beta-1a 125 μg | 38.5 | 41.9 | 47.0 | 21.2 | 41.4 | 27.9 |
Number of Participants With Adverse Events (AE)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can herefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. (NCT02587065)
Timeframe: Baseline up to Week 24
| Intervention | Participants (Count of Participants) |
|---|
| Peg-interferon Beta-1a 125 μg | 82 |
Change From Baseline in Adapted Sclerosis Treatment Concerns Questionnaire (MSTCQ) Score at Weeks 12 and 24
MSTCQ is a 20-item questionnaire adapted for 'Peg-interferon Beta 1a' containing two domains: injection system satisfaction (1-9) and side effects (1-11). All questions in the MSTCQ have a five-point response choice, with a minimum possible total score of 20 and a maximum possible total score of 100. Lower total scores indicating better outcomes. Questionnaires were completed electronically by participants, by means of a participant I-PAD at each study visit. Here, negative values indicate improvement in MSTCQ score from baseline. (NCT02587065)
Timeframe: Baseline, Weeks 12 and 24
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Change at Week 12 | Change at Week 24 |
|---|
| Peg-interferon Beta-1a 125 μg | 71.9 | -16.8 | -19.4 |
Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests
NAb testing only for those participants with a positive ADA test. Baseline is defined as the last non-missing measurement/assessment on the date of Week 26 Visit from study HZNP-ACT-301 (NCT02415127). If this measurement was missing or otherwise unavailable, it was the last non-missing measurement/assessment on or prior to first dose in this study. If the participant discontinued the study, then premature withdrawal assessments were mapped to the nearest scheduled visit based on schedule of the assessment and the study day. If the mapped visit was already available then the visit was mapped to the next schedule visit. Last on study assessment is the last non-missing post-baseline assessment for each participant. (NCT02593773)
Timeframe: Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]), Week 4, Week 13, Week 26, and Week 28 (follow-up safety visit)
| Intervention | participants (Number) |
|---|
| Baseline ADA = negative | Baseline ADA = positive | Baseline NAb = negative | Baseline NAb = positive | Week 4 ADA = negative | Week 4 ADA = positive | Week 13 ADA = negative | Week 13 ADA = positive | Week 26 ADA = negative | Week 26 ADA = positive | Week 28 (Follow-up) ADA = negative | Week 28 (Follow-up) ADA = positive | Last On Study Assessment ADA = negative | Last On Study Assessment ADA = positive |
|---|
| Interferon γ-1b | 85 | 1 | 1 | 0 | 84 | 0 | 79 | 0 | 64 | 0 | 56 | 0 | 85 | 0 |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
An adverse event (AE) is any untoward medical occurrence, whether or not the event is considered related to the investigational product. A TEAE is any adverse change from the subject's baseline condition, including any laboratory test value abnormality judged as clinically significant by the investigator, that occurs on or after the date of the first dose of study drug administered at home and throughout the duration of the clinical study, whether the adverse event is considered related to the treatment or not. An SAE is an AE that results in death, is life-threatening, results in persistent or significant disability or incapacity, inpatient hospitalization or prolongation of an existing hospitalization, is a congenital anomaly or birth defect, or other medically important event. (NCT02593773)
Timeframe: Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit)
| Intervention | participants (Number) |
|---|
| ≥ 1 TEAE | ≥ 1 Related TEAE | ≥ 1 SAE | ≥ 1 Related SAE | ≥ 1 TEAE Leading to Discontinuation | ≥ 1 TEAE Leading to Death |
|---|
| Interferon γ-1b | 78 | 61 | 4 | 0 | 1 | 1 |
Other Secondary Efficacy Endpoints: Number of ICU-free Days
Number of Intensive Care Unit free days up to Day 28, i.e. the patient is no longer receiving care in ICU. Patients who die during this period have been assigned a value of zero for the number of ICU care free days. (NCT02622724)
Timeframe: Day 28
| Intervention | Days (Median) |
|---|
| FP-1201-lyo 10 μg | 6 |
| Placebo | 3.5 |
Other Secondary Efficacy Endpoints: Days Free of Vasoactive Support
"Days without vasoactive support. The vasoactive support included catecholamine and non-catecholamine vasopressors, inotropes and vasodilating agents.~Overall, the median number of days free of vasoactive support was 20 days in the active group and 21 days in the placebo group." (NCT02622724)
Timeframe: Day 28
| Intervention | Days (Median) |
|---|
| FP-1201-lyo 10 μg | 20 |
| Placebo | 21 |
Other Secondary Efficacy Endpoints: Days Free of Renal Support
Days without renal support (any renal support was documented). Overall, the median number of days free of renal support was 28 days in the active group and 27 days in the placebo group. (NCT02622724)
Timeframe: Day 28
| Intervention | Days (Median) |
|---|
| FP-1201-lyo 10 μg | 28 |
| Placebo | 27 |
Other Secondary Efficacy Endpoints: Days Free of Organ Failure
The total number of days free of organ failure by Sequential Organ Failure Assessment (SOFA) methodology. Overall, the median number of days free of organ failure was 0 days in both the treatment groups. (NCT02622724)
Timeframe: Day 28 or last day in intensive care unit [ICU] if patient has left the ICU earlier than Day 28
| Intervention | Days (Median) |
|---|
| FP-1201-lyo 10 μg | 0 |
| Placebo | 0 |
Other Secondary Efficacy Endpoint: Days Free of Mechanical Ventilation
"The total number of days free of mechanical ventilation has been derived from the Patient Status report recorded on each day during the 28-day period. Patients who died during this period have been assigned a value of zero. This variable differs from the calculated Ventilation Free Days (VFD) endpoint, which contribute to the VDFsurv primary efficacy endpoint as it require additional conditions of unassisted breathing (UAB) to be met." (NCT02622724)
Timeframe: Day 28
| Intervention | Days (Median) |
|---|
| FP-1201-lyo 10 μg | 10 |
| Placebo | 9 |
Neurological Functioning (6MWT) at Extended Long-term Follow-up
The 6-minute walk test (6MWT) measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. According to the ERS/ATS technical standard to which the 6MWT was done, the walk test is done twice and the best result is used. It is an evaluation of the global and integrated responses of all systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood and neuromuscular units and muscle metabolism. The self-paced 6MWT assesses the sub- maximal level of functional capacity and will better reflect the functional exercise level for daily activities. ANOVA parameters estimates (LS Means and 90 % confidence intervals) for the overall treatment difference was analysed. (NCT02622724)
Timeframe: Day 360
| Intervention | maximal distance walked (meters) (Mean) |
|---|
| FP-1201-lyo 10 μg | 475 |
| Placebo | 453 |
Long-term Efficacy Endpoints Relating to Respiratory Functioning (FEV1)
Measuring FEV1 (forced expiratory volume in 1 second) assessed pulmonary function (airway obstruction, bronchoconstriction or bronchodilation). FEV1 is the volume exhaled during the first second of a forced expiratory manoeuvre, starting from the level of total lung capacity. (NCT02622724)
Timeframe: Day 180
| Intervention | %FEV1 (Mean) |
|---|
| FP-1201-lyo 10 μg | 81.2 |
| Placebo | 79.5 |
Long-term Efficacy Endpoints Relating to Neurological Functioning (6MWT)
The 6-minute walk test (6MWT) measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. According to the ERS/ATS technical standard to which the 6MWT was done, the walk test is done twice and the best result is used. It is an evaluation of the global and integrated responses of all systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood and neuromuscular units and muscle metabolism. The self-paced 6MWT assesses the sub- maximal level of functional capacity and will better reflect the functional exercise level for daily activities. ANOVA parameters estimates (LS Means and 90 % conf.interval) for the overall treatment difference was analysed. (NCT02622724)
Timeframe: Day 180
| Intervention | maximum distance walked (meters) (Mean) |
|---|
| FP-1201-lyo 10 μg | 449 |
| Placebo | 424 |
Long-term Efficacy Endpoint: Change in Quality of Life From Baseline to Day 180
Quality of Life was assessed through EQ-5D-3L (EuroQol 5-Dimensions 3-Levels questionnaire). An EQ Visual Analogue Scale (VAS) total score (ranging from 0-100) was measured (0= Worst imaginable health state, 100= Best imaginable health state). The EQ-5D-3L VAS scores are numerically summarised as change from pre-dose (Day 1) to long term follow-up (Day 180 visit). (NCT02622724)
Timeframe: Change from baseline to Day 180
| Intervention | change score on a scale (Median) |
|---|
| FP-1201-lyo 10 μg | -10 |
| Placebo | -5 |
Extended Long-term Follow-up Exploratory Endpoint: Change in Quality of Life From Baseline to Day 360
Quality of Life was assessed through EQ-5D-3L (EuroQol 5-Dimensions 3-Levels questionnaire). An EQ Visual Analogue Scale (VAS) total score (ranging from 0-100) was measured (0= Worst imaginable health state, 100= Best imaginable health state). The EQ-5D-3L VAS scores are numerically summarised as change from pre-dose (Day 1) to extended long term follow-up (Day 360 visit). (NCT02622724)
Timeframe: Change from baseline to Day 360
| Intervention | change score on a scale (Median) |
|---|
| FP-1201-lyo 10 μg | 0 |
| Placebo | 0 |
Extended Long-term Follow-up Endpoint: Respiratory Functioning (FEV1) at Day 360
Measuring FEV1 (forced expiratory volume in 1 second) assessed pulmonary function (airway obstruction, bronchoconstriction or bronchodilation). FEV1 is the volume exhaled during the first second of a forced expiratory manoeuvre, starting from the level of total lung capacity. (NCT02622724)
Timeframe: Day 360
| Intervention | %FEV1 (Mean) |
|---|
| FP-1201-lyo 10 μg | 69.4 |
| Placebo | 72.0 |
Exploratory, Extended Long-term Follow-up: Overall Mortality at Day 360
Fatalities; as the study was terminated early, the assessment time point for mortality at Day 360 was not reached. Therefore only the overall mortality at study termination is presented. (NCT02622724)
Timeframe: Day 360 /termination of study
| Intervention | Participants (Count of Participants) |
|---|
| FP-1201-lyo 10 μg | 51 |
| Placebo | 53 |
Efficacy Endpoint: Mortality in Hospital
This is the number of subjects who died in hospital (i.e. outside of Intensive Care Units) up to Day 28. (NCT02622724)
Timeframe: Up to Day 28
| Intervention | Participants (Count of Participants) |
|---|
| FP-1201-lyo 10 μg | 1 |
| Placebo | 0 |
Other Secondary Efficacy Endpoints: Number of Days in Hospital
Hospitalisation days (including the stay at Intensive Care Units). Patients who died during this period have been assigned a value of 28 for the number of days in ICU or in hospital. (NCT02622724)
Timeframe: Day 28
| Intervention | Days (Median) |
|---|
| FP-1201-lyo 10 μg | 28 |
| Placebo | 28 |
Efficacy Endpoint: Evaluation of Pharmacodynamic (PD) Using Myxovirus Resistance Protein A (MxA) Biomarker
Evaluation of MxA biomarker change from baseline to D14 between treatments arms over time. (NCT02622724)
Timeframe: From baseline to Day 14
| Intervention | ng/ml (Mean) |
|---|
| FP-1201-lyo 10 μg | 31.8 |
| Placebo | 7.8 |
Efficacy Endpoint: All-cause Mortality
Fatalities, mortality all-causes from randomisation up to Day 28 (NCT02622724)
Timeframe: At Day 28
| Intervention | percentage of subjects (Number) |
|---|
| FP-1201-lyo 10 μg | 26.4 |
| Placebo | 23 |
Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28
VFDsurv is a composite measure of all-cause mortality and the number of days free of mechanical ventilation (VFDsurv) within 28 days among survivors. Ventilator-free days (VFDs) correspond to those days when unassisted breathing (UAB) was possible for a complete calendar day. UAB was defined as: spontaneously breathing with face mask, nasal prong oxygen or room air, T-piece breathing, tracheostomy mask breathing, CPAP less than or equal to 5 cmH2O without pressure support or intermittent mandatory ventilation assistance, use of CPAP or BIPAP solely for sleep apnoea management. A patient was reported as ventilator-free after 2 consecutive calendar days of unassisted breathing (a VFD value of 0 is assigned to patients who die without initiating UAB or who require more than 28 days of mechanical ventilation. All patients who die before Day28 are assigned a VFDsurv value of -1). (NCT02622724)
Timeframe: Day 28
| Intervention | Days (Median) |
|---|
| FP-1201-lyo 10 μg | 10 |
| Placebo | 8.5 |
Change in the Treatment-specific Exploratory Biomarker Cluster of Differentiation 73 (CD73) Concentration
Evaluation of Cluster of differentiation 73 (CD73) change from baseline to D14 between treatments arms over time. (NCT02622724)
Timeframe: From baseline to Day 14
| Intervention | ng/ml (Mean) |
|---|
| FP-1201-lyo 10 μg | 6.2 |
| Placebo | 6.1 |
Evaluation of Safety: Physical Examination
"Physical examination data (covering the major body systems; general appearance, head [ear, nose and throat], cardiovascular, eyes, respiratory, abdomen, urogenital, musculoskeletal, neurological, lymph nodes and skin) were categorized as normal; abnormal, not clinically significant; abnormal, clinically significant or not done. Physical examinations were performed at Screening, then at the Last day in ICU and Day 28 (Out of ICU) or Early Termination, from which the last observation performed is derived. The changes from baseline to the last observations performed are categorized as no change, change clinically significant; change not clinically significant, not done." (NCT02622724)
Timeframe: From baseline to Last Observation Performed (D28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
| Intervention | Participants (Count of Participants) |
|---|
| General Appearance72565994 | General Appearance72565991 | Ear, Nose and Throat72565994 | Ear, Nose and Throat72565991 | Eyes72565991 | Eyes72565994 | Respiratory72565991 | Respiratory72565994 | Abdomen72565994 | Abdomen72565991 | Urogenital72565994 | Urogenital72565991 | Musculoskeletal72565991 | Musculoskeletal72565994 | Neurological72565991 | Neurological72565994 | Lymph nodes72565991 | Lymph nodes72565994 | Skin72565991 | Skin72565994 | Cardiovascular72565994 | Cardiovascular72565991 |
|---|
| No change | Change, Not Clinically Significant | Not available/pt died | Not done | Change, Clinically Significant |
|---|
| Placebo | 66 |
| FP-1201-lyo 10 μg | 8 |
| Placebo | 9 |
| Placebo | 8 |
| Placebo | 34 |
| FP-1201-lyo 10 μg | 67 |
| Placebo | 75 |
| Placebo | 1 |
| Placebo | 6 |
| FP-1201-lyo 10 μg | 34 |
| FP-1201-lyo 10 μg | 70 |
| Placebo | 76 |
| FP-1201-lyo 10 μg | 1 |
| FP-1201-lyo 10 μg | 2 |
| Placebo | 3 |
| FP-1201-lyo 10 μg | 35 |
| Placebo | 36 |
| FP-1201-lyo 10 μg | 27 |
| Placebo | 30 |
| Placebo | 28 |
| FP-1201-lyo 10 μg | 21 |
| Placebo | 26 |
| FP-1201-lyo 10 μg | 30 |
| Placebo | 33 |
| FP-1201-lyo 10 μg | 36 |
| FP-1201-lyo 10 μg | 65 |
| Placebo | 70 |
| Placebo | 2 |
| Placebo | 10 |
| FP-1201-lyo 10 μg | 31 |
| Placebo | 72 |
| FP-1201-lyo 10 μg | 6 |
| Placebo | 4 |
| FP-1201-lyo 10 μg | 32 |
| Placebo | 38 |
| FP-1201-lyo 10 μg | 59 |
| Placebo | 63 |
| FP-1201-lyo 10 μg | 11 |
| FP-1201-lyo 10 μg | 5 |
| FP-1201-lyo 10 μg | 33 |
| FP-1201-lyo 10 μg | 49 |
| Placebo | 55 |
| FP-1201-lyo 10 μg | 18 |
| Placebo | 14 |
| Placebo | 13 |
| FP-1201-lyo 10 μg | 69 |
| Placebo | 78 |
| FP-1201-lyo 10 μg | 0 |
| Placebo | 0 |
| FP-1201-lyo 10 μg | 39 |
| Placebo | 39 |
| Placebo | 35 |
| FP-1201-lyo 10 μg | 64 |
| Placebo | 64 |
| FP-1201-lyo 10 μg | 3 |
| Placebo | 37 |
| FP-1201-lyo 10 μg | 56 |
| Placebo | 60 |
| FP-1201-lyo 10 μg | 9 |
| Placebo | 12 |
| FP-1201-lyo 10 μg | 38 |
Evaluation of Safety: Laboratory Results
Laboratory safety assessments of biochemistry, haematology and urinalysis were performed daily during the stay at ICU. Laboratory data were classified according to normal ranges as out of range (OOR; not clinically significant), OOR (clinically significant), or OOR (clinically significant and an AE). Laboratory test results were summarised by actual results by baseline and last observation period. (NCT02622724)
Timeframe: From baseline to Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
| Intervention | Participants (Count of Participants) |
|---|
| Haemoglobin, Pre-Dose72565991 | Haemoglobin, Pre-Dose72565992 | Haemoglobin, LOP72565992 | Haemoglobin, LOP72565991 | Platelets, Pre-Dose72565991 | Platelets, Pre-Dose72565992 | Platelets, LOP72565991 | Platelets, LOP72565992 | Leucocytes, Pre-Dose72565991 | Leucocytes, Pre-Dose72565992 | Leucocytes, LOP72565991 | Leucocytes, LOP72565992 | Albumin, Pre-Dose72565991 | Albumin, Pre-Dose72565992 | Albumin, LOP72565991 | Albumin, LOP72565992 | Creatine Kinase, Pre-Dose72565992 | Creatine Kinase, Pre-Dose72565991 | Creatine Kinase, LOP72565992 | Creatine Kinase, LOP72565991 | Creatinine, Pre-Dose72565992 | Creatinine, Pre-Dose72565991 | Creatinine, LOP72565991 | Creatinine, LOP72565992 | Glucose, Pre-Dose72565992 | Glucose, Pre-Dose72565991 | Glucose, LOP72565992 | Glucose, LOP72565991 | Bilirubin, Pre-Dose72565991 | Bilirubin, Pre-Dose72565992 | Bilirubin, LOP72565991 | Bilirubin, LOP72565992 | AST, Pre-Dose72565991 | AST, Pre-Dose72565992 | AST, LOP72565992 | AST, LOP72565991 | ALT, Pre-Dose72565992 | ALT, Pre-Dose72565991 | ALT, LOP72565991 | ALT, LOP72565992 | Bicarbonate, Pre-Dose72565992 | Bicarbonate, Pre-Dose72565991 | Bicarbonate, LOP72565991 | Bicarbonate, LOP72565992 | Urine Protein, Pre-Dose72565991 | Urine Protein, Pre-Dose72565992 | Urine Protein, LOP72565991 | Urine Protein, LOP72565992 | Urine Glucose, Pre-Dose72565991 | Urine Glucose, Pre-Dose72565992 | Urine Glucose, LOP72565991 | Urine Glucose, LOP72565992 | Urine Blood, Pre-Dose72565991 | Urine Blood, Pre-Dose72565992 | Urine Blood, LOP72565991 | Urine Blood, LOP72565992 |
|---|
| OOR (NCS) | OOR (CS) | OOR (CS+AE) | Not available/pt died | Normal |
|---|
| FP-1201-lyo 10 μg | 22 |
| Placebo | 30 |
| FP-1201-lyo 10 μg | 103 |
| Placebo | 107 |
| FP-1201-lyo 10 μg | 19 |
| Placebo | 14 |
| Placebo | 0 |
| FP-1201-lyo 10 μg | 17 |
| Placebo | 18 |
| FP-1201-lyo 10 μg | 100 |
| Placebo | 117 |
| FP-1201-lyo 10 μg | 23 |
| Placebo | 16 |
| Placebo | 1 |
| FP-1201-lyo 10 μg | 85 |
| Placebo | 91 |
| FP-1201-lyo 10 μg | 43 |
| Placebo | 42 |
| FP-1201-lyo 10 μg | 16 |
| FP-1201-lyo 10 μg | 76 |
| Placebo | 65 |
| FP-1201-lyo 10 μg | 52 |
| FP-1201-lyo 10 μg | 10 |
| FP-1201-lyo 10 μg | 5 |
| FP-1201-lyo 10 μg | 1 |
| FP-1201-lyo 10 μg | 40 |
| FP-1201-lyo 10 μg | 72 |
| FP-1201-lyo 10 μg | 32 |
| Placebo | 36 |
| FP-1201-lyo 10 μg | 0 |
| Placebo | 57 |
| FP-1201-lyo 10 μg | 15 |
| Placebo | 21 |
| FP-1201-lyo 10 μg | 3 |
| FP-1201-lyo 10 μg | 2 |
| Placebo | 17 |
| FP-1201-lyo 10 μg | 83 |
| FP-1201-lyo 10 μg | 24 |
| Placebo | 15 |
| FP-1201-lyo 10 μg | 26 |
| Placebo | 25 |
| FP-1201-lyo 10 μg | 97 |
| FP-1201-lyo 10 μg | 59 |
| Placebo | 62 |
| Placebo | 45 |
| Placebo | 11 |
| FP-1201-lyo 10 μg | 33 |
| Placebo | 34 |
| FP-1201-lyo 10 μg | 82 |
| Placebo | 93 |
| FP-1201-lyo 10 μg | 45 |
| Placebo | 8 |
| FP-1201-lyo 10 μg | 4 |
| Placebo | 6 |
| FP-1201-lyo 10 μg | 78 |
| Placebo | 72 |
| FP-1201-lyo 10 μg | 41 |
| Placebo | 50 |
| Placebo | 28 |
| Placebo | 2 |
| FP-1201-lyo 10 μg | 69 |
| Placebo | 73 |
| Placebo | 64 |
| FP-1201-lyo 10 μg | 13 |
| FP-1201-lyo 10 μg | 56 |
| Placebo | 53 |
| Placebo | 85 |
| FP-1201-lyo 10 μg | 11 |
| Placebo | 10 |
| Placebo | 4 |
| FP-1201-lyo 10 μg | 65 |
| Placebo | 74 |
| FP-1201-lyo 10 μg | 71 |
| Placebo | 75 |
| FP-1201-lyo 10 μg | 7 |
| Placebo | 3 |
| FP-1201-lyo 10 μg | 88 |
| Placebo | 106 |
| FP-1201-lyo 10 μg | 37 |
| Placebo | 33 |
| FP-1201-lyo 10 μg | 9 |
| Placebo | 7 |
| FP-1201-lyo 10 μg | 114 |
| Placebo | 121 |
| Placebo | 23 |
| FP-1201-lyo 10 μg | 6 |
| Placebo | 5 |
| FP-1201-lyo 10 μg | 57 |
| Placebo | 52 |
| FP-1201-lyo 10 μg | 50 |
| Placebo | 70 |
| FP-1201-lyo 10 μg | 18 |
| Placebo | 76 |
| FP-1201-lyo 10 μg | 54 |
| Placebo | 56 |
| FP-1201-lyo 10 μg | 86 |
| Placebo | 92 |
| Placebo | 43 |
| Placebo | 9 |
| Placebo | 46 |
| Placebo | 12 |
| FP-1201-lyo 10 μg | 90 |
| Placebo | 97 |
| FP-1201-lyo 10 μg | 44 |
| Placebo | 47 |
| FP-1201-lyo 10 μg | 8 |
| FP-1201-lyo 10 μg | 89 |
| Placebo | 105 |
| FP-1201-lyo 10 μg | 47 |
| Placebo | 41 |
| Placebo | 54 |
| FP-1201-lyo 10 μg | 67 |
| FP-1201-lyo 10 μg | 20 |
| FP-1201-lyo 10 μg | 66 |
| Placebo | 84 |
| FP-1201-lyo 10 μg | 63 |
| Placebo | 123 |
| FP-1201-lyo 10 μg | 21 |
| Placebo | 19 |
| FP-1201-lyo 10 μg | 128 |
| Placebo | 135 |
| FP-1201-lyo 10 μg | 48 |
| Placebo | 58 |
| FP-1201-lyo 10 μg | 73 |
| Placebo | 77 |
Efficacy Endpoint: Mortality in ICU
All-cause mortality for subjects who died in Intensive Care Units up to Day 28. (NCT02622724)
Timeframe: Up to Day 28
| Intervention | percentage of subjects (Number) |
|---|
| FP-1201-lyo 10 μg | 25.7 |
| Placebo | 23.0 |
Post-Hoc Analyses Related to the Use of Concomitant Glucocorticoids Medications and Mortality at D28
The overall use of concomitant glucocorticoids treatment in both study treatment groups (active and placebo) were analysed. (NCT02622724)
Timeframe: Day 28
| Intervention | percentage of participants (Number) |
|---|
| Use of concomitant glucocorticoids | Mortality, with concomitant glucocorticoids | Mortality, without concomitant glucocorticoids |
|---|
| FP-1201-lyo 10 μg | 54.1 | 39.7 | 10.6 |
,| Placebo | 64.5 | 27.6 | 14.8 |
Pharmacogenetic Analysis
An optional genetic sample was analysed for subjects based on a separate consent. A carrier frequency was analysed for a C/T polymorphism (rs9984723) located in the 3'PRIME_UTR/intron region of IFNAR2-gene, which encodes the beta chain for the IFN-alpha/beta receptor and encompasses a regulatory motif for the glucocorticoid receptor. Biomarker responders were defined by a 3-fold elevation in MxA and a 2-fold in CD73 in comparison to baseline. (NCT02622724)
Timeframe: Anytime from baseline to Day 28
| Intervention | Participants (Count of Participants) |
|---|
| C-allele carrier | C-allele non-carrier |
|---|
| Biomarker Non-responder | 26 | 47 |
,| Biomarker Responder | 21 | 12 |
Exploratory Variables Relating to Efficacy: Composite Endpoint (Mortality and Days Free of Mechanical Ventilation) at Day 90
Composite endpoint including mortality and days free of mechanical ventilation (VFDsurv) within 90 days among survivors. Ventilation Free Survival at Day 90 has been classified as Dead, Alive but on a ventilator and Alive and breathing unassisted (NCT02622724)
Timeframe: Within 90 days
| Intervention | Participants (Count of Participants) |
|---|
| Dead | Alive-on ventilator | Alive-breathing unassisted |
|---|
| FP-1201-lyo 10 μg | 47 | 6 | 90 |
,| Placebo | 48 | 10 | 91 |
Evaluation of Safety: Vital Signs - Heart Rate
"Vital signs were measured supine pre-dose on Day 1 (baseline) and daily up to Day 28 while the patient was in the ICU. The results at baseline and at last observation performed (LOP) were summarized overall by treatment, variable and time point.~No statistical analyses were made for vital signs." (NCT02622724)
Timeframe: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
| Intervention | bpm (Mean) |
|---|
| Heart Rate, bpm : Pre-Dose | Heart Rate, bpm : LOP |
|---|
| FP-1201-lyo 10 μg | 93.4 | 92.5 |
,| Placebo | 94.8 | 92.7 |
Evaluation of Safety: Vital Signs - Body Temperature
"Vital signs were measured supine pre-dose on Day 1 (baseline) and daily up to Day 28 while the patient was in the ICU. The results at baseline and at last observation performed (LOP) were summarized overall by treatment, variable and time point.~No statistical analyses were made for vital signs." (NCT02622724)
Timeframe: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
| Intervention | degrees Celsius (Mean) |
|---|
| Body Temperature, degrees C : Pre-Dose | Body Temperature, degrees C : LOP |
|---|
| FP-1201-lyo 10 μg | 37.1 | 36.9 |
,| Placebo | 37.2 | 36.8 |
Evaluation of Safety: Vital Signs - Blood Pressure
"Vital signs were measured supine pre-dose on Day 1 (baseline) and daily up to Day 28 while the patient was in the ICU. The results at baseline and at last observation performed (LOP) were summarized overall by treatment, variable and time point.~No statistical analyses were made for vital signs." (NCT02622724)
Timeframe: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
| Intervention | mmHg (Mean) |
|---|
| Systolic Blood Pressure, mmHg: Pre-Dose | Systolic Blood Pressure, mmHg : LOP | Diastolic Blood Pressure, mmHg : Pre-Dose | Diastolic Blood Pressure, mmHg : LOP | Mean Arterial Pressure, mmHg : Pre-Dose | Mean Arterial Pressure, mmHg : LOP |
|---|
| FP-1201-lyo 10 μg | 114.6 | 124.3 | 58.9 | 65.1 | 76.5 | 82.7 |
,| Placebo | 110.2 | 120.3 | 55.6 | 62.6 | 73.6 | 80.8 |
Evaluation of Safety: Adverse Events and Deaths
Adverse events (AE) up to Day 28. Per protocol, AEs occurring after Day 28 if the investigator considered a causal relationship with the study drug as well as all deaths up to Day 360 were reported. Treatment-emergent AEs (TEAEs) were defined as AEs that begins or worsens in intensity after at least one dose of study drug has been administered. Serious AEs (SAEs) were defined as any untoward medical occurrence that at any dose resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was an important medical event. (NCT02622724)
Timeframe: AEs up to Day 28, only related after Day 28 and deaths up to Day 360
| Intervention | Participants (Count of Participants) |
|---|
| Subjects with TEAE | Subjects with AE considered related to study drug | Subjects with SAE | Death |
|---|
| FP-1201-lyo 10 μg | 130 | 41 | 77 | 51 |
,| Placebo | 132 | 33 | 77 | 53 |
Efficacy Endpoint: Presence of Neutralising Antibodies to IFN Beta-1a
The immunological response to FP-1201-lyo was assessed by monitoring presence of anti-drug binding antibodies (BAbs) and neutralising antibodies (NAbs) to IFN beta-1a on pre-dose Day 1 and at Day 28, the last day in ICU or early termination (if earlier). The BAbs were determined first, and if present, the NAbs were also determined. Presence of BAbs and NAbs were summarised categorically, using positive/negative classification. (NCT02622724)
Timeframe: Baseline and Day 28 (or last day in intensive care unit [ICU] or at withdrawal, if earlier)
| Intervention | Participants (Count of Participants) |
|---|
| Presence of BAbs to IFN β-1a at baseline | Presence of BAbs to IFN β-1a at Day28 | Presence of NAbs to IFN β-1a at baseline | Presence of NAbs to IFN β-1a at Day28 |
|---|
| FP-1201-lyo 10 μg | 2 | 0 | 1 | 0 |
,| Placebo | 2 | 1 | 0 | 0 |
Changes in Levels of Potential Inflammatory Markers (PIMs)
Evaluation of potential inflammatory markers (PIMs) change from baseline to D14 between treatments arms over time. Potential biomarkers included IL-1ra, IL-6, FGF basic, IP-10 and TNF-α. (NCT02622724)
Timeframe: From baseline to Day 14
| Intervention | pg/mL (Mean) |
|---|
| IL-1ra | IL-6 | FGF basic | IP-10 | TNF-α |
|---|
| FP-1201-lyo 10 μg | 1830 | 63 | 37 | 1938 | 68 |
,| Placebo | 1699 | 88 | 38 | 1762 | 81 |
Percentage of Participants With Best Overall Tumor Response
Tumor response was assessed as one of the following: Complete response (CR): disappearance of all target lesions and all pathological lymph nodes below 10 millimeter (mm). Partial response (PR): At least a 30 percent (%) decrease in the sum of diameters of target lesions. Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. (NCT02627144)
Timeframe: Baseline until progression or intolerable toxicity, whichever occurred first, assessed up to 6 years
| Intervention | percentage of participants (Number) |
|---|
| CR | PR | SD | PD | Not Evaluable |
|---|
| Advanced and/or Metastatic RCC Participants | 5.3 | 21.9 | 39.1 | 16.6 | 17.2 |
Progression-free Survival (PFS) Time
PFS time is defined as time between start of therapy and progression or death. Kaplan-Meier estimate was used for evaluation. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. (NCT02627144)
Timeframe: Baseline until progression or intolerable toxicity or death, whichever occurred first, assessed up to 6 years
| Intervention | months (Median) |
|---|
| Advanced and/or Metastatic RCC Participants | 10.2 |
Percentage of Participants With Disease Control
Disease control was defined as having achieved CR, PR, and/or SD during the course of the observation. CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. (NCT02627144)
Timeframe: Baseline until progression or intolerable toxicity, whichever occurred first, assessed up to 6 years
| Intervention | percentage of participants (Number) |
|---|
| Advanced and/or Metastatic RCC Participants | 66.3 |
Overall Survival (OS) Time
OS time is defined as time between start of therapy and date of death. Kaplan-Meier estimate was used for evaluation. (NCT02627144)
Timeframe: Baseline until progression or intolerable toxicity or death, whichever occurred first, assessed up to 6 years
| Intervention | months (Median) |
|---|
| Advanced and/or Metastatic RCC Participants | 28.7 |
Change From Baseline in Pain
Survey name: RAND 36-Item Health Survey (Version 1.0) Scale name: Pain Scale range: 0-100; Higher score means less pain (NCT02666768)
Timeframe: 6 months
| Intervention | change in units on the pain scale (Least Squares Mean) |
|---|
| Gamma Interferon-1b | -0.8 |
Percent Change From Baseline in Bone Mineral Density (BMD)
BMD measured by peripheral quantitative computed tomography (pQCT) in bone area w/ BMD<169mg/m3 (NCT02666768)
Timeframe: 6 months
| Intervention | percent change (Median) |
|---|
| Gamma Interferon-1b | 0 |
Change From Baseline in White Blood Cell Count (WBC)
(NCT02666768)
Timeframe: 6 months
| Intervention | x1000 cells/uL (Median) |
|---|
| Gamma Interferon-1b | -0.5 |
Time to Maximum Concentration (Tmax) of GPT
Tmax was obtained directly from the concentration-time data. (NCT02716779)
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
| Intervention | days (Median) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 2.8 |
| Placebo | 14.0 |
| Ribavirin | 3.0 |
Area Under the Concentration-Time Curve (AUC) of PEG-IFN
Evaluation of PEG-IFN arm after Day 0. Evaluation of ribavirin and placebo arms after Day 42. (NCT02716779)
Timeframe: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126
| Intervention | (nanogram/milliliter)*day ([ng/ml]*d) (Median) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 2097.9 |
| Placebo | 1270.4 |
| Ribavirin | 1164.9 |
Area Under the Concentration-Time Curve (AUC) of Glutamate-Pyruvate Transaminase (GPT)
(NCT02716779)
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
| Intervention | (Units/liter)*day ([U/L]*d) (Median) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 5078.3 |
| Placebo | 7233.5 |
| Ribavirin | 5231.3 |
Maximum Concentration (Cmax) of PEG-IFN
Cmax was obtained directly from the concentration-time data. Evaluation of PEG-IFN arm after day 0. Evaluation of ribavirin and placebo arms after day 42. (NCT02716779)
Timeframe: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126
| Intervention | ng/ml (Median) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 28.77 |
| Placebo | 20.36 |
| Ribavirin | 19.8 |
Maximum Concentration (Cmax) of Ribavirin
Cmax was obtained directly from the concentration-time data. Evaluation of ribavirin arm after day 0. Evaluation of placebo and PEG-IFN arms after day 42. (NCT02716779)
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
| Intervention | mcg/ml (Median) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 2.95 |
| Placebo | 2.83 |
| Ribavirin | 3.37 |
Time to Maximum Concentration (Tmax) of PEG-IFN
Tmax was obtained directly from the concentration-time data. Evaluation of PEG-IFN arm after day 0. Evaluation of ribavirin and placebo arms after day 42. (NCT02716779)
Timeframe: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126
| Intervention | weeks (Median) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 6.3 |
| Placebo | 12.0 |
| Ribavirin | 6.0 |
Time to Maximum Concentration (Tmax) of Ribavirin
Tmax was obtained directly from the concentration-time data. Evaluation of ribavirin arm after day 0. Evaluation of placebo and PEG-IFN arms after day 42. (NCT02716779)
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
| Intervention | weeks (Median) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 6.0 |
| Placebo | 8.0 |
| Ribavirin | 6.4 |
Area Under the Concentration-Time Curve (AUC) of Ribavirin
Evaluation of ribavirin arm after Day 0. Evaluation of placebo and PEG-IFN arms after Day 42. (NCT02716779)
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
| Intervention | (microgram/milliliter)*day ([mcg/ml]*d) (Median) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 186.6 |
| Placebo | 179.4 |
| Ribavirin | 290.1 |
Percentage of Participants With Treatment Response
HCV-RNA level was measured at each visit by a central laboratory. Treatment response was estimated applying the following definitions of response/non-response: 1) Adequate first phase decline: HCV RNA decline ≥ 0.5 log10 International Units/milliliter (IU/mL) from time 0 to 48 hours of PEG-IFN treatment (PEG-IFN arm: day 0 - day 2; placebo and ribavirin arm: day 42-day 44), 2) Rapid virologic response: HCV RNA < 15 IU/mL (=detection limit) on day 70, 3) Complete early virologic response: HCV RNA < 15 IU/mL on day 126, 4) Partial early virologic response (log decrease): HCV RNA decrease ≥ 2 log10 IU/mL from day 0 to day 126, 5) Partial early virologic response (cut off): HCV RNA <30000 IU/mL on day 126, 6) Non-response: HCV RNA decrease <2 log10 IU/mL from day 0 to day 126, 7) Null-response: HCV RNA decrease <1 log10 IU/mL from day 0 to day 28 and from day 0 to day 70 for PEG-IFN arm and placebo / ribavirin arm, respectively. (NCT02716779)
Timeframe: Up to Day 126
| Intervention | percentage of participants (Number) |
|---|
| Adequate first phase decline | Rapid virologic response | Complete early virologic response | Partial early virologic response (log decrease) | Partial early virologic response (cut off) | Non-response | Null responder |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 79 | 43 | 64 | 79 | 79 | 21 | 36 |
,| Placebo | 65 | 30 | 48 | 78 | 78 | 22 | 26 |
,| Ribavirin | 72 | 20 | 72 | 84 | 84 | 16 | 12 |
Maximum Concentration (Cmax) of GPT
Cmax was obtained directly from the concentration-time data. (NCT02716779)
Timeframe: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.
| Intervention | U/L (Median) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 68.5 |
| Placebo | 88.0 |
| Ribavirin | 75.0 |
Number of Patients Experiencing Reductions in Serum HBV DNA
To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on serum HBV DNA. (NCT02726789)
Timeframe: 48 weeks (treatment)
| Intervention | Participants (Count of Participants) |
|---|
| Experimental | 5 |
Number of Patients Experiencing Reductions in Serum HBsAg
To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on serum HBsAg. (NCT02726789)
Timeframe: 48 weeks (treatment)
| Intervention | Participants (Count of Participants) |
|---|
| Experimental | 5 |
Number of Patients Experiencing Treatment Emergent Laboratory Test Abnormalities or Adverse Events.
To record side effects, symptoms and adverse effects of exposure to REP 2139-Ca when combined pegylated interferon. (NCT02726789)
Timeframe: 48 weeks (treatment)
| Intervention | Participants (Count of Participants) |
|---|
| Experimental | 5 |
Number of Patients Experiencing Serum Anti-HBs > 10 mIU / ml
To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on anti-HBsAg antibody titer. (NCT02726789)
Timeframe: 48 weeks (treatment)
| Intervention | Participants (Count of Participants) |
|---|
| Experimental | 5 |
Number of Combined Unique Active Lesions
CUA (the number of new contrast-enhanced lesions on T1 images, and new or expanding lesions on T2 images (lesion identified on T1-and T2 images is not counted twice). (NCT02727907)
Timeframe: 16 weeks
| Intervention | lesions (Median) |
|---|
| BCD-033 | 0.0 |
| Rebif | 0.0 |
| Placebo | 1.0 |
Number of Combined Unique Active Lesions
Number of Combined Unique Active Lesions (CUA) -- the number of new MRI contrast uptake lesions on T1 images, and new or expanding lesions on T2 images (lesion identified on T1-and T2 images is not counted twice) after 52 weeks blinded application of interferon-β1а (BCD-033 and Rebif®) (44 mcg). (NCT02727907)
Timeframe: 52 weeks
| Intervention | lesions (Median) |
|---|
| BCD-033 | 0.0 |
| Rebif | 0.0 |
Relapse Free Time
"Time to first relapse in per protocol population" (NCT02727907)
Timeframe: 96 weeks
| Intervention | days (Median) |
|---|
| BCD-033 | 207.0 |
| Rebif/BCD-033 | 183.0 |
Serious Adverse Events
quantity and grade of all SAE is calculated in subjects, who received at least one dose of study drug (NCT02727907)
Timeframe: 52 week of study
| Intervention | adverse events (Number) |
|---|
| BCD-033 | 0 |
| Rebif/BCD-033 | 0 |
| Placebo/BCD-033 | 3 |
Annual Relapse Rate
Annual Relapse Rate ARR for 96 weeks was evaluated in two groups, after the administraion of IFN beta-1a in a full dose for 96 weeks. (NCT02727907)
Timeframe: 96 week
| Intervention | relapses (Mean) |
|---|
| BCD-033 | 0.208 |
| Rebif | 0.145 |
Severe Adverse Events Frequency
AE grade 3-4 (CTCAE 4.03)is calculated in subjects, who received at least one dose of study drug (NCT02727907)
Timeframe: 96 weeks
| Intervention | adverse events (Number) |
|---|
| BCD-033 | 2 |
| Rebif/BCD-033 | 3 |
Withdrawal
quantity of withdrawals due to AE/SAE is calculated in subjects, who received at least one dose of study drug (NCT02727907)
Timeframe: 16, 52 weeks
| Intervention | Participants (Count of Participants) |
|---|
| week 16 | week 52 |
|---|
| BCD-033 | 0 | 1 |
,| Placebo/BCD-033 | 1 | 2 |
,| Rebif | 1 | 1 |
Relapse Free Time
"Time to first relapse in per protocol population" (NCT02727907)
Timeframe: 16, 52 weeks
| Intervention | days (Median) |
|---|
| week 16 | week 52 |
|---|
| BCD-033 | 33.5 | 193.0 |
,| Placebo/BCD-033 | 15.0 | 74.0 |
,| Rebif | 14.0 | 123.5 |
Proportion of Subjects Without Confirmed Relapse
proportion of subjects without confirmed relapse in PP (NCT02727907)
Timeframe: 16, 52 weeks
| Intervention | Count of Participants (Number) |
|---|
| week 16 | week 52 |
|---|
| BCD-033 | 49 | 41 |
,| Placebo | 45 | 39 |
,| Rebif | 46 | 44 |
Immunogenicity
Count of Participants with Binding and Neutralizing Antibodies (NCT02727907)
Timeframe: 96 weeks
| Intervention | participants (Number) |
|---|
| Binding Antibodies | Neutralizing Antibodies |
|---|
| BCD-033 | 19 | 16 |
,| Rebif/BCD-033 | 14 | 13 |
Severe Adverse Events Frequency
AE grade 3-4 (CTCAE 4.03) is calculated in subjects, who received at least one dose of study drug (NCT02727907)
Timeframe: 52 weeks
| Intervention | adverse events (Number) |
|---|
| BCD-033 | 5 |
| Rebif | 4 |
| Placebo/BCD-033 | 7 |
Adverse Reaction/Serious Adverse Reactions
quantity and grade of all adverse reactions/serious adverse reactions is calculated in subjects, who received at least one dose of study drug (NCT02727907)
Timeframe: 16, 52 weeks
| Intervention | adverse events (Number) |
|---|
| week 16 | week 52 |
|---|
| BCD-033 | 67 | 92 |
,| Placebo/BCD-033 | 33 | 92 |
,| Rebif | 59 | 80 |
Immunogenicity
Count of Participants with Binding and Neutralizing Antibodies (NCT02727907)
Timeframe: 16, 52 weeks
| Intervention | participants (Number) |
|---|
| week 16 : Binding Antibodies | week 16 : Neutralizing Antibodies | week 52 : Binding Antibodies | week 52 : Neutralizing Antibodies |
|---|
| BCD-033 | 6 | 5 | 10 | 9 |
,| Placebo/BCD-033 | 2 | 2 | 7 | 7 |
,| Rebif/BCD-033 | 5 | 5 | 9 | 8 |
Adverse Events/Serious Adverse Events
quantity and grade of all AE/SAE is calculated in subjects, who received at least one dose of study drug (NCT02727907)
Timeframe: 96 weeks
| Intervention | adverse events (Number) |
|---|
| BCD-033 | 124 |
| Rebif/BCD-033 | 110 |
Annual Relapse Rate
Annual relapse rate ARR for 52 weeks was evaluated in all three groups, after the application of IFN beta-1a (NCT02727907)
Timeframe: 52 weeks
| Intervention | relapses (Mean) |
|---|
| BCD-033 | 0.113 |
| Rebif / BCD-033 | 0.091 |
| Placebo / BCD-033 | 0.109 |
Number of Combined Unique Active Lesions
CUA (the number of new contrast-enhanced lesions on T1 images, and new or expanding lesions on T2 images (lesion identified on T1-and T2 images is not counted twice) (NCT02727907)
Timeframe: 96 weeks
| Intervention | lesions (Median) |
|---|
| BCD-033 | 0.0 |
| Rebif/BCD-033 | 0.0 |
Withdrawal
quantity of withdrawals due to AE/SAE is calculated in subjects, who received at least one dose of study drug (NCT02727907)
Timeframe: 96 weeks
| Intervention | Participants (Count of Participants) |
|---|
| BCD-033 | 1 |
| Rebif/BCD-033 | 1 |
Percentage of Participants With HBsAg Seronegative at Weeks 48 and 72
Samples were collected and analyzed for HBsAg. Seronegative HBsAg is defined as below the level of detection of the assay. (NCT02732639)
Timeframe: At Weeks 48 and 72
| Intervention | percentage of participants (Number) |
|---|
| Seronegative HBsAg at Week 48 | Seronegative HBsAg at Week 72 |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 0 | 3.23 |
Number of Participants With Positive Hepatitis B Surface Antigen (HBsAg) Levels
Samples were collected and analyzed for HBsAg. Positive HBsAg levels are defined as levels above the level of detection of the assay. (NCT02732639)
Timeframe: At Screening and at Weeks 48 and 72
| Intervention | participants (Number) |
|---|
| HBsAg Positive at Screening | HBsAg Positive at Week 48 | HBsAg Positive at Week 72 |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 31 | 29 | 26 |
Percentage of Participants With Normal ALT at Week 48
Samples were collected and analyzed for ALT levels. A normal ALT is a value within the normal range of the assay. (NCT02732639)
Timeframe: At Week 48
| Intervention | percentage of participants (Number) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 45.16 |
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 72
Samples were collected and analyzed for ALT. A normal ALT is a value within the normal range of the assay. (NCT02732639)
Timeframe: At Week 72
| Intervention | percentage of participants (Number) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 54.84 |
Percentage of Participants With Negative Hepatitis D Virus Ribonucleic Acid (HDV RNA) at Week 72
Samples were collected and analyzed for HDV RNA levels. Negative HDV RNA is defined as below the level of detection of the assay. (NCT02732639)
Timeframe: At Week 72
| Intervention | percentage of participants (Number) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 61.29 |
Percentage of Participants With Negative HDV RNA at Week 48
Samples were collected and analyzed for HDV RNA levels. Negative HDV RNA is defined as below the level of detection of the assay. (NCT02732639)
Timeframe: At Week 48
| Intervention | percentage of participants (Number) |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 64.52 |
Percentage of Participants With Positive Hepatitis B Surface Antibody (HBsAb) at Weeks 48 and 72
Samples were collected and analyzed for HBsAb. Positive HBsAb levels are defined as levels above the level of detection of the assay and reflect the presence of antibodies produced against HBsAg. (NCT02732639)
Timeframe: At Weeks 48 and 72
| Intervention | percentage of participants (Number) |
|---|
| Positive HBsAb at Week 48 | Positive HBsAb at Week 72 |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 3.23 | 3.23 |
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Below 1*10^5 Copies/Milliliter (mL) at Weeks 48 and 72
Samples were collected and analyzed for HBV DNA levels. Reported here is the percentage of participants with HBV DNA levels below 1*10^5 copies/mL. (NCT02732639)
Timeframe: At Weeks 48 and 72
| Intervention | percentage of participants (Number) |
|---|
| HBV-DNA at Week 48 | HBV-DNA at Week 72 |
|---|
| Pegylated Interferon (PEG-IFN) Alfa-2a | 83.87 | 74.19 |
Percentage of Participants Without SVR Among Participants With Undetectable HCV RNA at the End of Treatment
"SVR was defined as having undetectable HCV RNA levels 24 weeks after completion of study treatment. HCV RNA levels were measured using Roche COBAS AMPLICOR HCV Test (limit of detection: 50 IU/mL). Percentage of participants without SVR among participants with undetectable HCV RNA at the end of treatment was reported (end of treatment = Week 48 for Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm and Week 72 for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm)." (NCT02761629)
Timeframe: "24 weeks after completion of study treatment (up to Week 72 for Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm and up to Week 96 for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm)"
| Intervention | percentage of participants (Number) |
|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | 52.6 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | 24.3 |
Percentage of Participants With Sustained Virologic Response (SVR)
SVR was defined as having un-detectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels 24 weeks after completion of study treatment. HCV RNA levels were measured using Roche COBAS AMPLICOR HCV Test (limit of detection: 50 International Units per milliliter [IU/mL]). Participants with detectable HCV RNA or without measurement at the end of the 24 week after completion of study treatment were considered as non-responders. (NCT02761629)
Timeframe: "24 weeks after completion of study treatment (up to Week 72 for Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm and up to Week 96 for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm)"
| Intervention | percentage of participants (Number) |
|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | 23.8 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | 36.5 |
Serum Human Immunodeficiency Virus (HIV) RNA Levels
HIV RNA levels were measured using Roche AMPLICOR MONITOR HIV-1 Test (limit of detection: 400 HIV-1 RNA copies/mL). Data for this outcome measure was to be reported up to 24 weeks after end of treatment visit (Week 72 for 'Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks' arm and Week 96 for 'Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks' arm). (NCT02761629)
Timeframe: "For Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm: Weeks 4, 12, 24, 48, and 72; for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm: Weeks 4, 12, 24, 48, 72, and 96"
| Intervention | Log10 copies per milliliter (Mean) |
|---|
| Baseline (n=12, 23) | Week 4 (n=6, 16) | Week 24 (n=9, 20) | Week 48 (n=11, 17) | Week 72 (n=10, 9) | Week 96 (n=0, 13) |
|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | 4.23 | 3.94 | 3.96 | 4.02 | 4.08 | NA |
,| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | 4.64 | 3.98 | 4.21 | 4.41 | 4.51 | 4.22 |
Percentage of Participants With Undetectable HCV RNA 12 Weeks After the Last Dose of Peg-IFN-Alpha-2A
HCV RNA levels were measured using Roche COBAS AMPLICOR HCV Test (limit of detection: 50 IU/mL). Participants with detectable HCV RNA or without measurement at the end of 12 weeks after the last dose of Peg-IFN-Alpha-2A were considered as non-responders. (NCT02761629)
Timeframe: "12 weeks after the last dose of Peg-IFN-Alpha-2A (up to Week 60 for Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm and up to Week 84 for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm)"
| Intervention | percentage of participants (Number) |
|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | 23.8 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | 36.5 |
Percentage of Participants With Undetectable HCV RNA
HCV RNA levels were measured using Roche COBAS AMPLICOR HCV Test (limit of detection: 50 IU/mL). Data for this outcome measure was to be reported up to end of treatment visit (Week 48 for 'Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks' arm and Week 72 for 'Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks' arm). (NCT02761629)
Timeframe: "For Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm: Weeks 4, 12, 24, and 48; for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm: Weeks 4, 12, 24, 48, and 72"
| Intervention | percentage of participants (Number) |
|---|
| Week 4 (n=73, 83) | Week 12 (n=73, 81) | Week 24 (n=73, 78) | Week 48 (n=68, 71) | Week 72 (n=0, 65) |
|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | 2.7 | 23.3 | 52.1 | 55.9 | NA |
,| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | 12.0 | 28.4 | 53.8 | 64.8 | 56.9 |
Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories
ALT levels were classified as: Normal Limit (NL) (as per laboratory standard), >1-2 Upper Normal Limit (ULN), >2-5 ULN, >5-10 ULN, and >10 ULN. Percentage of participants in each of these ALT level categories was reported. Data for this outcome measure was to be reported up to 24 weeks after end of treatment visit (Week 72 for 'Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks' arm and Week 96 for 'Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks' arm). (NCT02761629)
Timeframe: "For Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm: Weeks 4, 12, 24, 48, and 72; for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm: Weeks 4, 12, 24, 48, 72, and 96"
| Intervention | percentage of participants (Number) |
|---|
| Week 4, NL (n=70, 78) | Week 4, >1-2 ULN (n=70, 78) | Week 4, >2-5 ULN (n=70, 78) | Week 4, >5-10 ULN (n=70, 78) | Week 4, >10 ULN (n=70, 78) | Week 12, NL (n=76, 77) | Week 12, >1-2 ULN (n=76, 77) | Week 12, >2-5 ULN (n=76, 77) | Week 12, >5-10 ULN (n=76, 77) | Week 12, >10 ULN (n=76, 77) | Week 24, NL (n=74, 74) | Week 24, >1-2 ULN (n=74, 74) | Week 24, >2-5 ULN (n=74, 74) | Week 24, >5-10 ULN (n=74, 74) | Week 24, >10 ULN (n=74, 74) | Week 48, NL (n=65, 71) | Week 48, >1-2 ULN (n=65, 71) | Week 48, >2-5 ULN (n=65, 71) | Week 48, >5-10 ULN (n=65, 71) | Week 48, >10 ULN (n=65, 71) | Week 72, NL (n=59, 61) | Week 72, >1-2 ULN (n=59, 61) | Week 72, >2-5 ULN (n=59, 61) | Week 72, >5-10 ULN (n=59, 61) | Week 72, >10 ULN (n=59, 61) | Week 96, NL (n=0, 62) | Week 96, >1-2 ULN (n=0, 62) | Week 96, >2-5 ULN (n=0, 62) | Week 96, >5-10 ULN (n=0, 62) | Week 96, >10 ULN (n=0, 62) |
|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | 50.0 | 40.0 | 10.0 | 0.0 | 0.0 | 61.8 | 27.6 | 10.5 | 0.0 | 0.0 | 70.3 | 27.0 | 2.7 | 0.0 | 0.0 | 67.7 | 24.6 | 7.7 | 0.0 | 0.0 | 52.5 | 27.1 | 20.3 | 0.0 | 0.0 | NA | NA | NA | NA | NA |
,| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | 52.6 | 38.5 | 9.0 | 0.0 | 0.0 | 62.3 | 29.9 | 5.2 | 1.3 | 1.3 | 63.5 | 28.4 | 6.8 | 0.0 | 1.4 | 69.0 | 26.8 | 2.8 | 1.4 | 0.0 | 68.9 | 27.9 | 3.3 | 0.0 | 0.0 | 50.0 | 35.5 | 12.9 | 1.6 | 0.0 |
Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96
Data for this outcome measure was to be reported up to 24 weeks after end of treatment visit (Week 72 for 'Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks' arm and Week 96 for 'Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks' arm). (NCT02761629)
Timeframe: "For Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm: Baseline, Weeks 4, 12, 24, 48, and 72; for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm: Baseline, Weeks 4, 12, 24, 48, 72, and 96"
| Intervention | Cells per cubic millimeter (cells/mm^3) (Mean) |
|---|
| Baseline (n=78, 81) | Change at Week 4 (n=69, 74) | Change at Week 12 (n=68, 75) | Change at Week 24 (n=69, 68) | Change at Week 48 (n=61, 67) | Change at Week 72 (n=58, 55) | Change at Week 96 (n=0, 62) |
|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | 578.7 | -148.2 | -185.4 | -206.7 | -209.4 | 9.5 | NA |
,| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | 546.2 | -88.0 | -164.5 | -178.4 | -196.4 | -167.5 | -15.1 |
Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96
Data for this outcome measure was to be reported up to 24 weeks after end of treatment visit (Week 72 for 'Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks' arm and Week 96 for 'Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks' arm). (NCT02761629)
Timeframe: "For Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm: Baseline, Weeks 4, 12, 24, 48, and 72; for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm: Baseline, Weeks 4, 12, 24, 48, 72, and 96"
| Intervention | Ratio (Mean) |
|---|
| Baseline (n=78, 81) | Change at Week 4 (n=69, 74) | Change at Week 12 (n=68, 75) | Change at Week 24 (n=69, 68) | Change at Week 48 (n=61, 67) | Change at Week 72 (n=58, 55) | Change at Week 96 (n=0, 62) |
|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | 0.67 | 0.11 | 0.22 | 0.36 | 0.43 | 0.12 | NA |
,| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | 0.68 | 0.09 | 0.20 | 0.29 | 0.30 | 0.36 | 0.09 |
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
An adverse event (AE) is any untoward medical occurrence, whether or not the event is considered related to the investigational product. A TEAE is any adverse change from the subject's baseline condition, including any laboratory test value abnormality judged as clinically significant by the investigator, that occurs on or after the date of the first dose of study drug administered at home and throughout the duration of the clinical study, whether the adverse event is considered related to the treatment or not. A serious AE (SAE) is an AE that results in death, is life-threatening, results in persistent or significant disability or incapacity, inpatient hospitalization or prolongation of an existing hospitalization, is a congenital anomaly or birth defect, or other medically important event. (NCT02797080)
Timeframe: Baseline/Day 1 (Week 28 Follow-Up Visit for Study HZNP-ACT-302 ([NCT02593773]) through end of study; mean (SD) duration of treatment was 99.2 (58.48) days.
| Intervention | participants (Number) |
|---|
| ≥ 1 TEAE | ≥ 1 Related TEAE | ≥ 1 SAE | ≥ 1 Related SAE | ≥ 1 TEAE Leading to Discontinuation | ≥ 1 TEAE Leading to Death |
|---|
| Interferon γ-1b | 21 | 7 | 0 | 0 | 0 | 0 |
Number of Participants With Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship to the study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; Life-threatening experience (immediate risk of dying); Persistent or significant disability or incapacity; and congenital anomaly. (NCT02829775)
Timeframe: Baseline up to approximately 3 years
| Intervention | participants (Number) |
|---|
| Interferon Alfa-2A in Cancer Participants | 1 |
Number of Participants With Overall Tumor Response
Tumor response was assessed every 6 months using hematological evaluation or any other appropriate diagnostic techniques, as per standard of care practice. The complete response (CR) and partial response (PR) status were recorded from case report form. (NCT02829775)
Timeframe: Baseline until disease progression, withdrawal or death, whichever occurred earlier (assessed every 6 months up to approximately 3 years)
| Intervention | participants (Number) |
|---|
| CR | PR |
|---|
| Interferon Alfa-2A in Cancer Participants | 9 | 0 |
Incidence of Adverse Events
Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. (NCT03063632)
Timeframe: Up to 2 years and 1 months
| Intervention | Participants (Count of Participants) |
|---|
| Group I (Pembrolizumab, Interferon Gamma-1b) | 15 |
| Group II (Pembrolizumab, Interferon Gamma-1b) | 12 |
Time to Response (TTR)
Will use simple statistics. (NCT03063632)
Timeframe: Time interval between the date of first treatment and the date of response (complete response [CR]/partial response [PR]), up to 2 years
| Intervention | days (Median) |
|---|
| Group I (Pembrolizumab, Interferon Gamma-1b) | 126 |
Rate of Overall Response Duration Beyond 12 Months (ORR12)
Will be assessed per global assessment of mycosis fungoides and Sezary syndrome (confirmed & investigator assessed). Will use binomial distribution. (NCT03063632)
Timeframe: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date beyond 12 months that recurrent disease is objectively documented, up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Group I (Pembrolizumab, Interferon Gamma-1b) | 2 |
| Group II (Pembrolizumab, Interferon Gamma-1b) | 0 |
Progression-free Survival (PFS)
Will be assessed using the Kaplan-Meier method (NCT03063632)
Timeframe: Time from enrollment to disease progression or death, whichever occurs earlier, based upon investigator assessment, up to 3 years
| Intervention | days (Median) |
|---|
| Group I (Pembrolizumab, Interferon Gamma-1b) | 394.0 |
| Group II (Pembrolizumab, Interferon Gamma-1b) | 196.5 |
Overall Response Rate (ORR)
"Participants in Treatment Group 1 will be assessed for response and progression using standard response criteria in patients with Mycosis Fungoides and Sezary syndrome. Per Global Response Score determined by evaluating skin, lymph nodes, internal organs (viscera), and blood specimens: Complete Response (CR), complete disappearance of all clinical evidence of disease; Partial Response (PR), regression of measurable disease.~Participants in Treatment Group 2 will be assessed for response and progression using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Complete Response (CR) disappearance of all lesions and no new lesion; Partial Response (PR), 30% or greater reduction in tumor size and no new lesions.~The ORR is defined as CR combined with PR. Will be assessed using binomial proportion.~Best response at any timepoint was used to determine ORR." (NCT03063632)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Group I (Pembrolizumab, Interferon Gamma-1b) | 6 |
| Group II (Pembrolizumab, Interferon Gamma-1b) | 0 |
Event-free Survival (EFS)
Will be assessed using the Kaplan-Meier method. (NCT03063632)
Timeframe: Termination due to toxicity, initiation of next significant treatment, progressive disease, or death of any cause, up to 2 years
| Intervention | days (Median) |
|---|
| Group I (Pembrolizumab, Interferon Gamma-1b) | 185.5 |
| Group II (Pembrolizumab, Interferon Gamma-1b) | 73.0 |
Duration of Response (DOR)
Will be assessed using the Kaplan-Meier method. (NCT03063632)
Timeframe: Time interval between the date of first response (CR/PR) and the date of progression, up to 2 years and 11 months
| Intervention | days (Median) |
|---|
| Group I (Pembrolizumab, Interferon Gamma-1b) | 505.0 |
Number of Patients With Treatment Emergent Adverse Events Occurring in Two or More Patients [Safety]
To evaluate the number of patients with toxicity events while on SV-BR-1-GM, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) (NCT03066947)
Timeframe: Through study completion, an average of 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Patients with Adverse Events | Erythema injection site | Pruritis injection site | Induration injection site | Fatigue | Nausea | Constipation | Abdominal pain | Flu like symptoms | Diarrhea | GGTP increased | Injection site reaction | Urinary Tract Infection | Vomiting | Abdominal distension | Alkaline Phosphatase Increased | ALT Increased | Anorexia | AST Increased | Back Pain | Chills | Decreased appetite | Dehydration | Dizziness | Erythema Multiforme | Glucose increased | Hematocrit Decreased | Hypercalcemia | Lymphocytes Decreased | Myalgia | Pleural Effusion |
|---|
| SV-BR-1-GM Monotherapy | 24 | 11 | 8 | 7 | 6 | 6 | 5 | 4 | 4 | 3 | 3 | 3 | 3 | 3 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 |
Rate of Non-progression of Tumors
Non-progressive rate, defined as CR, PR or stable disease (SD) per RECIST and iRECIST criteria (NCT03066947)
Timeframe: Through study completion, an average of 1 year
| Intervention | Participants (Count of Participants) |
|---|
| SV-BR-1-GM Monotherapy | 4 |
Durability of Tumor Response
Durability of response, as defined as complete response (disappearance of all tumors), partial response (30% or greater reduction in the sum of diameters of target lesions (tumors) with stable disease in non-target lesions) or stable disease (less than 20% increase in the sum of diameters of target lesions with no new lesions appearing) by evaluating those patients eligible to complete the optional treatments from 9-12 months (NCT03066947)
Timeframe: Through study completion, an average of 1 year
| Intervention | days (Median) |
|---|
| SV-BR-1-GM Monotherapy | 105.5 |
Objective Tumor Response Rate
Objective response rate (ORR), defined as complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors (RECIST) and immune-related RECIST (iRECIST) criteria. (NCT03066947)
Timeframe: Through study completion, an average of 1 year
| Intervention | Participants (Count of Participants) |
|---|
| SV-BR-1-GM Monotherapy | 0 |
Duration of Treatment Emergent Adverse Events [Safety]
To evaluate the duration of toxicity events while on SV-BR-1-GM, as defined by CTCAE (NCT03066947)
Timeframe: Through study completion, an average of 1 year
| Intervention | Days (Median) |
|---|
| Median Duration | 8 |
Phase 1: Recommended Phase 2 Dose (RP2D)
The dose limiting toxicity (DLT) evaluation period for dose escalation will be during the first three weeks. The maximum tolerated dose (MTD) dose level is defined as the highest dose level with ≤1 out of 6 participants experiencing a DLT. If the first dose level experience two or more DLTs, then dose de-escalation will occur. DLT during cycle one (C1) is defined as follows: Non-hematologic or hematologic toxicities that are ≥ grade 3 in severity and probably or definitely related to study therapy which leads to chemotherapy treatment delays > 14 days are considered DLT. The MTD will become the RP2D. (NCT03112590)
Timeframe: 12 weeks
| Intervention | mcg/m^2 (Number) |
|---|
| Combination Therapy | 75 |
Phase 2: Clinical Response
Complete Response (CR) and Partial Response (PR) based upon tumor measurements obtained on physical examination at baseline, after completion of 4 cycles of study therapy. Factors that will be evaluated include: Breast mass(es) - size (longest dimension); Axillary lymph node(s) - size (longest dimension); Skin edema of the breast - present worse, present unchanged, present improved, or absent; Skin erythema of the breast - present worse, present unchanged, present improved, or absent. (NCT03112590)
Timeframe: 12 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease |
|---|
| Phase 2 | 25 | 11 | 2 | 1 |
Phase 2: Progression Free Survival (PFS)/Number of Participants Who Progressed
"Progression will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.~PFS is defined as the time from study therapy to the first occurrence of ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause. This is reported as number of participants who progressed." (NCT03112590)
Timeframe: Up to 2 years
| Intervention | participants (Number) |
|---|
| Phase 2 | 1 |
Phase 2: Pathologic Complete Response Rate (pCR)
"Pathologic complete response in the breast at definitive surgery after completion of protocol therapy. The pathologic response to treatment will be assessed by an institutional pathologist at Moffitt Cancer Center. The pathologist will evaluate response by the Residual Cancer Burden(RCB) for each participant as described in the online calculator (see RCB link in the More Information section). pCR is defined as no residual invasive carcinoma in the breast and lymph notes at definitive surgery following neoadjuvant therapy" (NCT03112590)
Timeframe: After post therapy surgery - Therapy: approximately 12 weeks per participant
| Intervention | percentage of participants (Number) |
|---|
| Combination Therapy | 52 |
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples
CD73 (ecto-5'-nucleotidase enzyme) concentration (NCT03119701)
Timeframe: Day 0 up to Day 13
| Intervention | ng/mL (Geometric Mean) |
|---|
| Baseline | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | Day 9 | Day 13 |
|---|
| FP-1201-lyo 10 µg | 2.1 | 2.0 | 2.2 | 2.0 | 2.3 | 3.0 | 3.8 | 3.9 | 2.9 |
,| FP-1201-lyo Placebo | 2.2 | 2.2 | 2.2 | 2.3 | 2.6 | 3.5 | 3.8 | 3.8 | 2.7 |
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis
Number of days receiving hemodialysis. There were only few reported values other than zero. (NCT03119701)
Timeframe: Day 30 and Day 90
| Intervention | days (Mean) |
|---|
| Day 30 | Day 90 |
|---|
| FP-1201-lyo 10 µg | 0.9 | 0.6 |
,| FP-1201-lyo Placebo | 0.0 | 0.0 |
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP)
Intra-abdominal pressure values, which were routinely measured during ICU stay via urine bladder catheter. (NCT03119701)
Timeframe: Days 1 - 6, D9 and D13 during Intensive Care Unit (ICU) stay
| Intervention | mmHg (Mean) |
|---|
| Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 |
|---|
| FP-1201-lyo Placebo | 10.3 | 12.1 | 10.3 | 8.6 | 12.5 | 15.0 |
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP)
Intra-abdominal pressure values, which were routinely measured during ICU stay via urine bladder catheter. (NCT03119701)
Timeframe: Days 1 - 6, D9 and D13 during Intensive Care Unit (ICU) stay
| Intervention | mmHg (Mean) |
|---|
| Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | Day 9 | Day 13 |
|---|
| FP-1201-lyo 10 µg | 15.4 | 12.2 | 13.1 | 11.4 | 10.5 | 11.4 | 11.0 | 10.8 |
Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters
Number of TEAEs from vital signs data, laboratory data, physical examinations and spontaneous reporting when conscious. (NCT03119701)
Timeframe: Day 0 to Day 30
| Intervention | Events (Number) |
|---|
| Product-related TEAEs | Severe TEAEs | Serious TEAEs | TEAEs Leading to Study Product Discontinuation | TEAEs Leading to Death |
|---|
| FP-1201-lyo 10 µg | 17 | 28 | 26 | 7 | 7 |
,| FP-1201-lyo Placebo | 1 | 2 | 5 | 1 | 1 |
The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Number of fatalities (NCT03119701)
Timeframe: Day 30
| Intervention | Participants (Count of Participants) |
|---|
| FP-1201-lyo 10 µg | 6 |
| FP-1201-lyo Placebo | 2 |
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker
Concentration of Myxovirus Resistant Protein A (MxA) (NCT03119701)
Timeframe: Day 0 up to Day 13
| Intervention | ng/mL (Geometric Mean) |
|---|
| Baseline | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | Day 9 | Day 13 |
|---|
| FP-1201-lyo 10 µg | 3.5 | 15.0 | 19.8 | 21.2 | 36.4 | 48.3 | 50.4 | 14.3 | 3.9 |
,| FP-1201-lyo Placebo | 6.0 | 5.1 | 3.8 | 3.3 | 4.1 | 3.1 | 3.6 | 4.8 | 8.7 |
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Organ Failure Free Days by Means of the Sequential Organ Failure Assessment (SOFA) Score
"Organ failure free days were defined as the number of days in the first 30 days after the first dose of study medication that the patient was alive and free of organ failure with a SOFA score of zero for the following six organ parameters: respiration, coagulation, liver, cardiovascular, central nervous system and renal function. It is graded from 0 to 4 according to the degree of dysfunction/ failure (higher scores indicate more severe organ failure). Patients who died without achieving a SOFA score of zero was assigned an organ failure free days value of zero.~Note: the information for organ failure free days has been only collected when the patients have been in the Intensive Care Unit (ICU). As ICU free days have been reported in a separate variable, it was decided that presented information will be kept, without trying to conduct imputation." (NCT03119701)
Timeframe: Day 30
| Intervention | days (Mean) |
|---|
| FP-1201-lyo 10 µg | 0.0 |
| FP-1201-lyo Placebo | 0.0 |
The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Number of fatalities (NCT03119701)
Timeframe: Day 90
| Intervention | Participants (Count of Participants) |
|---|
| FP-1201-lyo 10 µg | 7 |
| FP-1201-lyo Placebo | 2 |
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs)
Number of ventilator free days. VFDs to Day 30 were defined as the number of calendar days after initiating unassisted breathing (UAB) to Day 30 from first treatment, assuming that a patient survives at least 48 consecutive hours after initiating UAB. Patients who die without initiating UAB were assigned a VFD value of zero. (NCT03119701)
Timeframe: Day 30
| Intervention | days (Median) |
|---|
| FP-1201-lyo 10 µg | 25.0 |
| FP-1201-lyo Placebo | 29.0 |
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS).
Scale gives the degree of disability or dependence in the daily activities. Single mRS value is applied for every patient based on patient or caregiver interview. The scale runs from 0-6, from perfect health without symptoms to death. Pre-operation Baseline Visit mRS value is collected for reference. (NCT03119701)
Timeframe: Day 90
| Intervention | Participants (Count of Participants) |
|---|
| No symptoms - 0 | No significant disability - 1 | Slight disability - 2 | Moderate disability - 3 | Moderately severe disability - 4 | Severe disability - 5 | Death - 6 |
|---|
| FP-1201-lyo 10 µg | 5 | 5 | 3 | 2 | 3 | 2 | 7 |
,| FP-1201-lyo Placebo | 2 | 5 | 1 | 0 | 0 | 1 | 2 |
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples
IFN beta-1a neutralizing antibodies immune response. Blood samples for the NAbs assessments were collected at Day 0 pre-dose (baseline) and at Day 30. (NCT03119701)
Timeframe: Day 30
| Intervention | Participants (Count of Participants) |
|---|
| Baseline | Day 30 |
|---|
| FP-1201-lyo 10 µg | 0 | 0 |
,| FP-1201-lyo Placebo | 0 | 0 |
Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples
IL-6 concentration. (NCT03119701)
Timeframe: Day 0 up to Day 13
| Intervention | pg/mL (Geometric Mean) |
|---|
| Baseline | Day 1 | Day 3 | Day 6 | Day 9 |
|---|
| FP-1201-lyo 10 µg | 328.9 | 493.1 | 181.4 | 164.1 | 107.9 |
,| FP-1201-lyo Placebo | 378.9 | 460.2 | 130.7 | 79.1 | 74.5 |
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Months 4 and 8
EDSS is an ordinal scale in half-point increments that qualifies disability in participants with MS. It consists of 8 ordinal rating scales assessing seven functional systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other). EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicated worst outcomes. (NCT03368664)
Timeframe: Baseline, Months 4 and 8
| Intervention | scores on scale (Mean) |
|---|
| Month 4 | Month 8 |
|---|
| Alemtuzumab | 0.05 | 0.00 |
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Participants With New or Enlarged T2 Lesions Per MRI Scan
Number of participants with at least one new or enlarged T2 lesions per MRI scan was reported in this outcome measure. Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during treatment period divided by the total number of scans performed during treatment period. (NCT03368664)
Timeframe: Period 1: Month -4 up to Month 0, Period 2: Month 4 to Month 8
| Intervention | Participants (Count of Participants) |
|---|
| Period 1 | 10 |
| Period 2 | 3 |
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan
Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during a specified period divided by the total number of scans performed during that specified period. (NCT03368664)
Timeframe: Period 1: Month -4 up to Month 0, Period 2: Month 4 to Month 8
| Intervention | lesions per scan (Number) |
|---|
| Period 1 | 3.53 |
| Period 2 | 0.13 |
Progression Free Survival
Will be treated as bivariate time-to-event data and will be summarized using standard Kaplan-Meier methods. (NCT03403634)
Timeframe: From the start of treatment until disease progression (defined by RECIST 1.1) or last-follow-up, assessed up to 12 months
| Intervention | Months (Median) |
|---|
| Treatment (Celecoxib, Interferon Alfa-2b, Rintatolimod) | 1.5 |
Overall Survival
Will be treated as bivariate time-to-event data and will be summarized using standard Kaplan-Meier methods. (NCT03403634)
Timeframe: From the start of treatment until death due to any cause or last follow-up, assessed up to 12 months
| Intervention | Months (Median) |
|---|
| Treatment (Celecoxib, Interferon Alfa-2b, Rintatolimod) | 10.5 |
Change in Tumor-infiltrating Lymphocytes (TILs) in the Colorectal Cancer Lesions
"The TILs will be summarized by time-point (pre-/post-treatment) using the mean, median, standard deviation; and graphically using dot-plots.~The TIL of interest is CD8a expression, which is reported as the mean fold change from pre-treatment (i.e. post treatment / pre treatment)." (NCT03403634)
Timeframe: Baseline up to 12 months
| Intervention | fold change (Mean) |
|---|
| Treatment (Celecoxib, Interferon Alfa-2b, Rintatolimod) | 7.25 |
Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Will be treated as binary data and summarized using frequencies and relative frequencies; with the ORR estimated using a 90% confidence interval obtained using Jeffrey's prior method. (NCT03403634)
Timeframe: Up to 12 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Celecoxib, Interferon Alfa-2b, Rintatolimod) | 0 |
Serious Adverse Events
Number of participants with treatment-related serious adverse events by laboratory tests and physician examination (NCT03480932)
Timeframe: 16 weeks for SOF+DAC+PEG and 24 weeks for SOF+DAC
| Intervention | Participants (Count of Participants) |
|---|
| SOF+DAC+PEG | 0 |
| SOF+DAC, DOT | 0 |
| SOF+DAC, Standard | 0 |
Medication Adherence
Adherence to medication regimen defined using a combination of the biometric data for Arms 1 and 2 and self-report and pill counts for Arm 3. Percentage reporting at least 90% adherence (NCT03480932)
Timeframe: 4 weeks for SOF+DAC+PEG and 12 weeks for SOF+DAC
| Intervention | Participants (Count of Participants) |
|---|
| SOF+DAC+PEG | 35 |
| SOF+DAC, DOT | 31 |
| SOF+DAC, Standard | 10 |
SVR12
Percentage of participants achieving sustained virologic response 12 weeks quantification) after treatment is completed (SVR12) as assessed by HCV RNA less than the lower limit of quantification measured 12 weeks after treatment completion (NCT03480932)
Timeframe: 12 weeks after treatment completion, 16 weeks for SOF+DAC+PEG and 24 weeks for SOF+DAC
| Intervention | Participants (Count of Participants) |
|---|
| SOF+DAC+PEG | 26 |
| SOF+DAC, DOT | 30 |
| SOF+DAC, Standard | 17 |
Number of Participants Achieving Sustained Responder Status at 24 Weeks of Follow-up
The number of participants achieving sustained responder status at 24 weeks of follow-up was assessed. A participant was classified as a sustained responder if, at 24 weeks of follow-up, they met both of the following criteria: 1) HCV-RNA negative (defined as <100 copies/mL serum by qPCR assay); and 2) ALT level normal. (NCT03537274)
Timeframe: Up to 72 weeks (up to 48 weeks treatment and 24 weeks follow-up)
| Intervention | Participants (Count of Participants) |
|---|
| PEG-Intron, 0.5 mg/kg | 52 |
| PEG-Intron, 1.0 mg/kg | 70 |
| PEG-Intron, 1.5 mg/kg | 69 |
| Interferon Alfa-2b | 37 |
Number of Participants Achieving Responder Status at 24 Weeks of Treatment
The number of participants achieving responder status at 24 weeks of treatment was assessed. A participant was classified as a responder if, at 24 weeks of treatment, they met both of the following criteria: 1) HCV-Ribonucleic Acid (RNA) negative (defined as <100 copies/mL serum by quantitative polymerase chain reaction [qPCR] assay); and 2) alanine transaminase (ALT) level normal. (NCT03537274)
Timeframe: Up to 24 weeks
| Intervention | Participants (Count of Participants) |
|---|
| PEG-Intron, 0.5 mg/kg | 80 |
| PEG-Intron, 1.0 mg/kg | 87 |
| PEG-Intron, 1.5 mg/kg | 90 |
| Interferon Alfa-2b | 59 |
Number of Participants With Cytogenetic Response (CR) to PEG Intron and Intron A at 6 Months
Cytogenetic response (CR) at 6 months, as at 12 months, was defined by the degree of suppression of Philadelphia chromosome (Ph^1) achieved during study treatment. The determination of CR at 6 months was based on cytogenetic analysis of bone marrow aspirate samples. The CR criteria were based on the percentage (%) of PH^1-positive cells during study treatment. Protocol-defined CR criteria were Complete (0%), Partial (1-34%), Minor (35-90%), or No Response (>90%). Data for the analysis population was based on the intent-to-treat principle. Participants who were treatment failures at 6 months were considered cytogenetic non-responders. Recording of CR was independent of hematologic responses. (NCT03547154)
Timeframe: 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response: 0% Ph+ | Partial Response: 1-34% Ph+ | Minor Response: 35-90% Ph+ | No Response: >90% Ph+ | Participant with Missing Data |
|---|
| INTRON A (Interferon Alfa-2b) | 7 | 19 | 51 | 48 | 48 |
,| PEG Intron (Pegylated Interferon Alfa-2b) | 3 | 23 | 37 | 61 | 47 |
Number of Participants With Overall Survival
Participants were followed for survival; those who did not achieve a major cytogenetic response were discontinued from the study. For participants who completed 1 year of study treatment and continued to Year 2 and beyond, survival and disease progression every 3 months were assessed, and serious adverse events (SAEs) were reported. Participants were followed until resolution of any drug-related nonserious adverse event, and any SAE occurring while on the study or within 30 days of last dose of study drug. Participant death during survival follow-up was reported to the drug safety unit of the Sponsor. Each participant (whether discontinued or still on treatment) was followed every 3 months for survival and disease progression information. Overall survival was analyzed using the log-rank statistic, and the hazard ratio (HR) and 95% confidence interval (CI) for the HR were obtained using Cox's proportional hazards model. (NCT03547154)
Timeframe: Up to 2 years (24 months), and beyond
| Intervention | Participants (Count of Participants) |
|---|
| Deaths | Survivors |
|---|
| INTRON A (Interferon Alfa-2b) | 15 | 158 |
,| PEG Intron (Pegylated Interferon Alfa-2b) | 17 | 154 |
Number of Participants With Hematologic Responses to PEG Intron and Intron A at 6 Months
Hematologic response at 6 months was assessed, while the hematologic response was measured at 3, 6, 9 and 12 months during the first year of study treatment. To be considered a hematologic responder a participant must have met all of the following criteria for a minimum of 28 days: WBC count <10,000/μL; platelet count <450,000/L; normal differential count in peripheral blood (manual differential count); no palpable spleen. Participants achieving a complete hematologic response at 3 months had the cytogenetic response evaluated at 3 months as well. Participants who achieved a complete hematologic response by 6 months continued treatment for another 6 months. Participants who failed to achieve a complete hematologic response after 6 months of treatment were considered treatment failures, and further treatment for this group was at the discretion of the treating physician. Participants may have continued to receive their assigned study medication for an additional 6 months. (NCT03547154)
Timeframe: 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Treatment Failure | Missing |
|---|
| INTRON A (Interferon Alfa-2b) | 98 | 44 | 31 |
,| PEG Intron (Pegylated Interferon Alfa-2b) | 91 | 52 | 28 |
Overall Survival
Overall survival (OS) is the time from randomization to death due to any cause. Participants were to be followed for survival every 3 months. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. After the early termination of the study, participants were followed for safety only. Although the OS analysis is not in the clinical study report due to early termination of the study, an OS ad hoc analysis was requested by the FDA and is therefore presented in this outcome measure. Below table presents the median duration of survival for participants. (NCT03552549)
Timeframe: From time of randomization to time of death (up to approximately 26 months)
| Intervention | Months (Median) |
|---|
| PEG-Intron | NA |
| INTRON A | 23.72 |
Number of Participants Who Discontinued Treatment Due to an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. (NCT03554005)
Timeframe: Up to 40 Weeks
| Intervention | Participants (Count of Participants) |
|---|
| PEG Interferon Alfa-2b 0.75 mcg/kg OW | 0 |
| PEG Interferon Alfa-2b 1.5 mcg/kg OW | 0 |
| PEG Interferon Alfa-2b 3 mcg/kg OW | 0 |
| PEG Interferon Alfa-2b 4.5 mcg/kg OW | 0 |
| PEG Interferon Alfa-2b 6 mcg/kg OW | 0 |
| PEG Interferon Alfa-2b 7.5 mcg/kg OW | 3 |
Number of Participants Who Experienced an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. (NCT03554005)
Timeframe: Up to 42 Weeks
| Intervention | Participants (Count of Participants) |
|---|
| PEG Interferon Alfa-2b 0.75 mcg/kg OW | 1 |
| PEG Interferon Alfa-2b 1.5 mcg/kg OW | 2 |
| PEG Interferon Alfa-2b 3 mcg/kg OW | 1 |
| PEG Interferon Alfa-2b 4.5 mcg/kg OW | 2 |
| PEG Interferon Alfa-2b 6 mcg/kg OW | 11 |
| PEG Interferon Alfa-2b 7.5 mcg/kg OW | 11 |
Best Objective Response
Best Objective Response data were based on World Health Organization (WHO) criteria and included four categories. Complete Response (CR) was the disappearance of all clinically detectable malignant disease. Partial Response (PR) was a decrease of ≥50% of the sum of products of largest perpendicular diameters of all bidimensionally measurable lesions; and a decrease of ≥50% in sum of largest diameters of all unidimensionally measure lesions. Stable Disease (SD) was a <50% decrease or <25% increase in sum of products of largest perpendicular diameters of all bidimensionally measurable lesions; or a <50% decrease or <25% increase in sum of diameters of all unidimensionally measurable lesions. In addition, no new lesions appeared. Progressive Disease (PD) was a ≥25% increase in size of at least one bidimensionally or unidimensionally measurable lesion or appearance of new lesion. Occurrence of pleural effusion or ascites was also considered PD if substantiated by positive cytology. (NCT03554005)
Timeframe: Up to 40 Weeks
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Not Evaluated |
|---|
| PEG Interferon Alfa-2b 0.75 mcg/kg OW | 0 | 0 | 1 | 0 | 0 |
,| PEG Interferon Alfa-2b 1.5 mcg/kg OW | 0 | 0 | 2 | 0 | 0 |
,| PEG Interferon Alfa-2b 3 mcg/kg OW | 1 | 0 | 0 | 0 | 1 |
,| PEG Interferon Alfa-2b 4.5 mcg/kg OW | 0 | 1 | 0 | 1 | 0 |
,| PEG Interferon Alfa-2b 6 mcg/kg OW | 3 | 0 | 6 | 1 | 1 |
,| PEG Interferon Alfa-2b 7.5 mcg/kg OW | 0 | 4 | 4 | 2 | 1 |
Number of Participants With Reduction in Fibroscan Transient Elastography Values
Reduction in Fibroscan transient elastography values by >25% of baseline at end of therapy. (NCT03600714)
Timeframe: Baseline and 24 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 4 |
Number of Participants With Normalization of Serum ALT
Normalization of serum ALT (ALT <20 in females and ALT <31 in males) at the end of therapy, at week 12 of posttherapy follow-up and at week 24 of post-therapy follow-up, OR reduction in serum ALT by >50% of baseline at week 12 of post therapy follow up and week 24 of post therapy follow up. (NCT03600714)
Timeframe: End of therapy, and 12 and 24 weeks after completing therapy
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 2 |
Change in Quantitative Log HBsAg Levels From Baseline 24 Weeks After Completing Therapy
Change in quantitative log HBsAg levels at from baseline to 24 weeks after completing therapy (NCT03600714)
Timeframe: Baseline and 24 weeks after completing therapy
| Intervention | log IU/mL (Mean) |
|---|
| Treatment | 0.16 |
Change in Quantitative Log HBsAg Levels From Baseline to Week 24
Change in quantitative log HBsAg levels at from baseline to week 24 (NCT03600714)
Timeframe: Baseline and week 24
| Intervention | log IU/mL (Mean) |
|---|
| Treatment | 0.15 |
Number of Participants Who Discontinue Medication
Discontinuation of the medication before 24 weeks by the clinical team or patient will be considered a failure to tolerate the medicine. (NCT03600714)
Timeframe: 24 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 3 |
Number of Participants With Reduction in Histologic Inflammatory Scores (Modified HAI)
Reduction in histologic inflammatory scores (modified HAI) by at least two points with no progression in histologic fibrosis (Ishak) at week 24 post-treatment follow-up. (NCT03600714)
Timeframe: End of treatment and 24 weeks after completing therapy.
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 6 |
Number of Participants With Decline of Hepatitis D Virus (HDV) RNA Viral Titer of >2 Logs
Decline of HDV RNA viral titer of >2 logs from baseline at 24 weeks of therapy (NCT03600714)
Timeframe: Baseline and 24 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 18 |
Number of Participants With Loss of HBsAg at 24 Weeks After Completing Therapy
Loss of HBsAg from the serum at 24 weeks after completing therapy (NCT03600714)
Timeframe: 24 weeks after completing therapy
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 0 |
Number of Participants With Loss of HBsAg at Week 12 Weeks After Completing Therapy
Loss of HBsAg from the serum at 12 weeks after completing therapy (NCT03600714)
Timeframe: 12 weeks after completing therapy
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 0 |
Number of Participants With Loss of HBsAg at Week 24
Loss of HBsAg from the serum at week 24 (NCT03600714)
Timeframe: Week 24
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 0 |
Number of Participants With Reduction of Hepatic Venous Pressure Gradient (HVPG)
Reduction in hepatic venous pressure gradient (HVPG) measurements by >25% of baseline OR normalization of HVPG (<5 mm Hg) at 24 weeks after completing therapy (NCT03600714)
Timeframe: Baseline and 24 weeks after completing therapy
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 10 |
Number of Participants With Sustained Virologic Response
Undetectable HDV RNA at both 12 and 24 weeks post treatment follow-up visits (NCT03600714)
Timeframe: 12 and 24 weeks after completing therapy
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 3 |
Number of Patients With Pathological Complete Response (pCR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI, where Complete Response (CR) corresponds to the disappearance of all target lesions. (NCT04081389)
Timeframe: Up to 4 week post-treatment (with a range of 7 to 11 weeks).
| Intervention | Participants (Count of Participants) |
|---|
| Arm 1: Interferon Alpha-2b at DL 1 | 0 |
| Arm 2: Interferon Alpha-2b at DL 2 | 1 |
| Arm 3: Interferon Alpha-2b at DL 3 | 2 |
| Arm 4: Interferon Alpha-2b at DL 4 | 2 |
Recurrence-free Survival (RFS)
RFS is defined as local/regional invasive recurrence, invasive ipsilateral breast tumor recurrence, distant recurrence, inoperable (meaning no surgery because of progression), and/or death from breast cancer (per standard of care according to physician discretion) or any cause. RFS will be calculated from the time of treatment to event. The median RFS was estimated using standard Kaplan-Meier methods (where NR = not reached). (NCT04081389)
Timeframe: At 3 years
| Intervention | months (Median) |
|---|
| Arm 1: Interferon Alpha-2b at DL 1 | 12.0 |
| Arm 2: Interferon Alpha-2b at DL 2 | NA |
| Arm 3: Interferon Alpha-2b at DL 3 | 11.4 |
| Arm 4: Interferon Alpha-2b at DL 4 | 11.5 |
Overall Survival (OS)
OS is defined by death from breast cancer, non-breast cancer, unknown, or any other cause and will be calculated from the time of study entry to event. The median OS is estimated using standard Kaplan-Meier methods (where NR = not reached). (NCT04081389)
Timeframe: At 3 years
| Intervention | months (Median) |
|---|
| Arm 1: Interferon Alpha-2b at DL 1 | 21.7 |
| Arm 2: Interferon Alpha-2b at DL 2 | NA |
| Arm 3: Interferon Alpha-2b at DL 3 | NA |
| Arm 4: Interferon Alpha-2b at DL 4 | NA |
Number of Patients With Dose Limiting Toxicities
"Safety and toxicity will be assessed using the CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE Version 5.0). The resulting dose limiting toxicity (DLT) information is used to identify the appropriate dose level of CKM and paclitaxel for future clinical exploration.~The following events will be considered a DLT:~The event occurs within 3 weeks following 1st dose of combination CKM + paclitaxel therapy and subsequent enrollment for dose-escalation will only proceed after the 3-week period has been completed.~The toxicity has been determined by the investigator to be possibly, probably or definitely related to celecoxib, rintatolimod, interferon-α2b or paclitaxel.~Any death not clearly due to th" (NCT04081389)
Timeframe: Within 21 days of treatment adminstration
| Intervention | Participants (Count of Participants) |
|---|
| Arm 1: Interferon Alpha-2b at DL 1 | 0 |
| Arm 2: Interferon Alpha-2b at DL 2 | 0 |
| Arm 3: Interferon Alpha-2b at DL 3 | 0 |
| Arm 4: Interferon Alpha-2b at DL 4 | 0 |
Undetectable COVID PCR Testing at Day 14
Negative COVID PCR testing 14 days after first lambda dose (NCT04343976)
Timeframe: 14 days
| Intervention | Participants (Count of Participants) |
|---|
| Lambda Treatment | 2 |
| Saline Placebo | 2 |
Undetectable COVID PCR at Day 7
Negative COVID PCR testing 7 days after first lambda dose (NCT04343976)
Timeframe: 7 days
| Intervention | Participants (Count of Participants) |
|---|
| Lambda Treatment | 1 |
| Saline Placebo | 4 |
Undetectable COVID PCR at Day 3
Negative COVID PCR testing 3 days after first lambda dose (NCT04343976)
Timeframe: 3 days
| Intervention | Participants (Count of Participants) |
|---|
| Lambda Treatment | 1 |
| Saline Placebo | 4 |
Change From Baseline in Basophils
Blood to evaluate basophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | 10^9 cells/liter (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.000 | 0.002 | 0.015 | 0.009 | 0.021 | 0.027 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.003 | 0.011 | 0.004 | 0.022 | 0.007 | 0.049 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.001 | 0.009 | 0.010 | 0.016 | 0.027 | 0.031 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.002 | 0.003 | 0.007 | 0.015 | 0.022 | 0.028 |
Change From Baseline in Aspartate Aminotransferase (AST)
Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The measure was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | U/L (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 8.0 | 13.2 | -6.2 | -12.6 | -10.9 | -10.8 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | -5.1 | -11.3 | -10.8 | -27.2 | -19.0 | -26.3 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | -4.6 | -5.2 | -16.5 | -13.5 | -13.9 | -15.8 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | -10.0 | -19.8 | -20.6 | -26.3 | -30.8 | -22.2 |
Change From Baseline in Alanine Aminotransferase (ALT)
Blood to evaluate ALT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The measure was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | Units/Liter (U/L) (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 17.6 | 41.4 | 18.8 | 9.9 | 3.5 | -3.2 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 2.6 | 1.5 | 4.0 | -15.1 | -4.9 | -9.3 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 5.0 | 13.5 | 5.3 | 9.0 | 2.6 | -6.4 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 10.9 | 3.8 | -8.7 | -11.1 | -17.6 | -13.8 |
Time to Recovery for Patients With a Baseline Ordinal Score of 4 and 5
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 5.0 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 5.0 |
Duration of Hospitalization
Duration of hospitalization was determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Including imputations for participants who died | Among participants who did not die |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 6 | 6 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 28 | 16.5 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 6 | 6 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 10 | 10 |
Change in National Early Warning Score (NEWS) From Baseline
The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15, 22, and 29
| Intervention | units on a scale (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 22 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | -0.7 | -1.1 | -1.4 | -1.6 | -1.6 | -1.5 | -1.7 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 1.0 | 1.6 | 1.7 | 1.4 | 1.9 | 1.6 | 1.9 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | -0.6 | -1.0 | -1.3 | -1.4 | -1.6 | -1.6 | -1.9 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | -0.7 | -1.3 | -0.6 | -1.0 | -1.5 | -1.7 | -1.8 |
Change From Baseline in C-reactive Protein (CRP)
Blood to evaluate CRP was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The measure was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | mg/L (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | -44.3 | -59.0 | -63.8 | -65.6 | -66.6 | -69.2 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | -46.6 | -55.6 | -57.4 | -36.0 | -27.8 | -46.5 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | -40.0 | -58.2 | -63.3 | -66.6 | -65.6 | -70.2 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | -37.6 | -40.5 | -69.3 | -75.6 | -72.1 | -76.8 |
Time to an Improvement of One Category Using an Ordinal Scale
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Time to improvement by at least one category was determined for each participant. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 12.0 |
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 15.0 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 12.0 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 5.0 |
Proportion of Participants With New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use
Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use was assessed among participants not on ventilator or extracorporeal membrane oxygenation (ECMO) use at baseline. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Proportion of participants (Number) |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.04 |
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.54 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.05 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.15 |
Proportion of Participants With New Oxygen Use
Incidence of new oxygen use was assessed as for participants in Ordinal Score 4 and 5 who were not on oxygen at baseline. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Proportion of participants (Number) |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.51 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.57 |
Proportion of Participants With New Non-invasive Ventilation or High Flow Oxygen Use
Proportion of participants with new non-invasive ventilation or high flow oxygen use was assessed as for participants in Ordinal Score 4 and 5. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Proportion of participants (Number) |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.15 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.15 |
Percentage of Participants Reporting Serious Adverse Events (SAEs)
An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | percentage of participants (Number) |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 14.7 |
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 60.0 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 13.3 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 24.2 |
Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs)
Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | percentage of participants (Number) |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 38.9 |
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 60.0 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 31.7 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 36.4 |
28-day Participant Mortality
The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Proportion of participants (Number) |
|---|
| Remdesivir Plus Interferon Beta-1a | 0.05 |
| Remdesivir Plus Placebo | 0.03 |
14-day Participant Mortality
The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates (NCT04492475)
Timeframe: Day 1 through Day 15
| Intervention | Proportion of participants (Number) |
|---|
| Remdesivir Plus Interferon Beta-1a | 0.02 |
| Remdesivir Plus Placebo | 0.02 |
Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 5
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. (NCT04492475)
Timeframe: Day 5
| Intervention | percentage of participants (Number) |
|---|
| Death at or before study visit | Hospitalized, on invasive mech. vent. or ECMO | Hospitalized, on non-invasive vent./high flow O2 | Hospitalized, requiring supplemental oxygen | Hospitalized, not on O2, requiring ongoing care | Hospitalized, not requiring O2, no longer req care | Not hospitalized, limit on activities/req home O2 | Not hospitalized, no limitations on activities |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.2 | 1.8 | 8.4 | 49.1 | 26.5 | 0.7 | 13.3 | 0.0 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 2.9 | 37.1 | 48.6 | 11.4 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.7 | 2.7 | 8.7 | 46.2 | 26.3 | 0.0 | 15.2 | 0.2 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.0 | 14.7 | 58.8 | 20.6 | 0.0 | 0.0 | 5.9 | 0.0 |
Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 1
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. (NCT04492475)
Timeframe: Day 1
| Intervention | percentage of participants (Number) |
|---|
| Death at or before study visit | Hospitalized, on invasive mech. vent. or ECMO | Hospitalized, on non-invasive vent./high flow O2 | Hospitalized, requiring supplemental oxygen | Hospitalized, not on O2, requiring ongoing care | Hospitalized, not requiring O2, no longer req care | Not hospitalized, limit on activities/req home O2 | Not hospitalized, no limitations on activities |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.0 | 0.0 | 81.4 | 18.6 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.0 | 0.0 | 100 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.0 | 0.0 | 84.8 | 15.2 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.0 | 0.0 | 100 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
Change From Baseline in Total Bilirubin
Blood to evaluate total bilirubin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | mg/dL (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | -0.08 | -0.07 | -0.03 | 0.00 | 0.09 | -0.01 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.07 | 0.03 | 0.10 | 0.16 | 0.34 | 0.01 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | -0.07 | 0.00 | 0.04 | 0.09 | 0.03 | -0.06 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.03 | 0.02 | 0.04 | -0.01 | 0.13 | 0.03 |
Change From Baseline in Prothrombin International Normalized Ratio (INR)
Blood to evaluate INR was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | ratio (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | -0.03 | -0.03 | -0.07 | 0.05 | -0.09 | -0.07 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.05 | 0.02 | 0.01 | 0.02 | 0.02 | 0.00 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.07 | 0.09 | 0.04 | 0.06 | -0.09 | -0.10 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | -0.08 | -0.08 | 0.02 | 0.05 | 0.01 | -0.11 |
Change From Baseline in Platelets
Blood to evaluate platelets was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The outcome was assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | 10^9 cells/liter (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 46.5 | 82.1 | 96.8 | 70.9 | 29.4 | 56.7 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 38.4 | 63.9 | 45.2 | 20.0 | -40.0 | 52.4 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 57.6 | 97.8 | 126.8 | 98.9 | 33.3 | 52.3 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 58.8 | 82.2 | 92.0 | 61.2 | -14.5 | 4.5 |
Change From Baseline in Neutrophils
Blood to evaluate neutrophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | 10^9 cells/liter (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | -0.622 | -0.307 | 0.187 | 2.069 | -0.383 | -1.779 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | -0.324 | -0.123 | 1.712 | 3.419 | 1.311 | -1.867 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.329 | 1.096 | 2.583 | 2.612 | 0.165 | -1.492 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.479 | 0.323 | 2.312 | 1.146 | -0.004 | -3.317 |
Change From Baseline in Monocytes
Blood to evaluate monocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | 10^9 cells/liter (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.157 | 0.229 | 0.301 | 0.381 | 0.207 | 0.131 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.112 | 0.136 | 0.147 | 0.365 | 0.107 | 0.310 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.127 | 0.212 | 0.311 | 0.403 | 0.212 | 0.114 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.179 | 0.172 | 0.348 | 0.333 | 0.262 | 0.015 |
Change From Baseline in Lymphoctyes
Blood to evaluate lymphocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | 10^9 cells/liter (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.301 | 0.492 | 0.390 | 0.536 | 0.655 | 0.863 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.237 | 0.289 | 0.281 | 0.347 | 0.384 | 0.575 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.227 | 0.470 | 0.404 | 0.486 | 0.679 | 0.909 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.137 | 0.242 | 0.377 | 0.867 | 0.642 | 0.873 |
Change From Baseline in Hemoglobin
Blood to evaluate hemoglobin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | grams/deciliter (g/dL) (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | -0.19 | -0.04 | -0.34 | -0.71 | -0.58 | -0.39 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | -0.14 | -0.47 | -1.13 | -1.98 | -3.18 | -3.89 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | -0.20 | -0.13 | -0.29 | -0.47 | -0.43 | -0.13 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | -0.10 | -0.81 | -1.01 | -1.32 | -2.65 | -1.15 |
Change From Baseline in Eosinophils
Blood to evaluate eosinophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | 10^9 cells/liter (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.011 | 0.016 | 0.043 | 0.044 | 0.116 | 0.189 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.014 | 0.037 | 0.028 | 0.117 | 0.135 | 0.291 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.013 | 0.032 | 0.041 | 0.063 | 0.130 | 0.172 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.006 | 0.019 | 0.038 | 0.105 | 0.166 | 0.199 |
Change From Baseline in Creatinine
Blood to evaluate serum creatinine was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The measure was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | mg/dL (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | -0.076 | -0.122 | -0.144 | -0.205 | -0.049 | -0.075 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.054 | 0.121 | 0.415 | 0.361 | 0.099 | -0.182 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | -0.069 | -0.077 | -0.109 | -0.103 | -0.057 | -0.029 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | -0.074 | -0.050 | 0.005 | -0.004 | 0.178 | 0.140 |
Time to an Improvement of Two Categories Using an Ordinal Scale
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Time to improvement by at least two categories was determined for each participant. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 13.0 |
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | NA |
| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 13.0 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 14.0 |
Time to Discharge or to a National Early Warning Score (NEWS) of
The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. The time to discharge or a NEWS of less than or equal to 2 was determined for each participant. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 4.0 |
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | NA |
| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 4.0 |
| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 9.0 |
Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Remdesivir Plus Interferon Beta-1a | 5.0 |
| Remdesivir Plus Placebo | 5.0 |
Change From Baseline in White Blood Cell Count (WBC)
Blood to evaluate WBC was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15 and 29
| Intervention | 10^9 cells/liter (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | -0.166 | 0.486 | 1.037 | 3.145 | 0.649 | -0.470 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.255 | 0.434 | 3.062 | 4.420 | 3.030 | -0.472 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.720 | 1.894 | 3.529 | 3.646 | 1.211 | -0.294 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.856 | 0.908 | 3.261 | 3.153 | 1.562 | -2.123 |
Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Sex
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Male | Female |
|---|
| Remdesivir Plus Interferon Beta-1a | 5.0 | 4.5 |
,| Remdesivir Plus Placebo | 5.0 | 5.0 |
Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Race
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Asian | Black or African American | White | Other |
|---|
| Remdesivir Plus Interferon Beta-1a | 8.0 | 4.0 | 4.0 | 6.0 |
,| Remdesivir Plus Placebo | 8.0 | 4.0 | 5.0 | 5.0 |
Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Ethnicity
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Not Hispanic or Latino | Hispanic or Latino |
|---|
| Remdesivir Plus Interferon Beta-1a | 5.0 | 6.0 |
,| Remdesivir Plus Placebo | 5.0 | 5.0 |
Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 8
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. (NCT04492475)
Timeframe: Day 8
| Intervention | percentage of participants (Number) |
|---|
| Death at or before study visit | Hospitalized, on invasive mech. vent. or ECMO | Hospitalized, on non-invasive vent./high flow O2 | Hospitalized, requiring supplemental oxygen | Hospitalized, not on O2, requiring ongoing care | Hospitalized, not requiring O2, no longer req care | Not hospitalized, limit on activities/req home O2 | Not hospitalized, no limitations on activities |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.2 | 2.7 | 4.4 | 24.1 | 11.9 | 0.7 | 56.0 | 0.0 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 5.7 | 45.7 | 22.9 | 14.3 | 2.9 | 0.0 | 8.6 | 0.0 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.9 | 2.9 | 7.4 | 21.0 | 9.8 | 0.2 | 57.8 | 0.0 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 5.9 | 11.8 | 29.4 | 26.5 | 8.8 | 0.0 | 17.6 | 0.0 |
Change From Baseline in D-dimer Concentration
Blood to evaluate d-dimer concentration was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. (NCT04492475)
Timeframe: Days 1, 3, 5, 8, 11, 15, and 29
| Intervention | mg/L fibrinogen-equivalent units (FEU) (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | -0.2 | -0.2 | -0.2 | -0.2 | -0.2 | -0.1 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 2.2 | -4.0 | -9.9 | -10.9 | -9.1 | -8.9 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.1 | 0.2 | 0.2 | 0.1 | -0.1 | 0.1 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.5 | 0.8 | 0.0 | -0.3 | -0.3 | -0.4 |
Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 3
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. (NCT04492475)
Timeframe: Day 3
| Intervention | percentage of participants (Number) |
|---|
| Death at or before study visit | Hospitalized, on invasive mech. vent. or ECMO | Hospitalized, on non-invasive vent./high flow O2 | Hospitalized, requiring supplemental oxygen | Hospitalized, not on O2, requiring ongoing care | Hospitalized, not requiring O2, no longer req care | Not hospitalized, limit on activities/req home O2 | Not hospitalized, no limitations on activities |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.0 | 0.9 | 6.0 | 74.1 | 18.8 | 0.2 | 0.0 | 0.0 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.0 | 17.1 | 80.0 | 2.9 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.2 | 1.6 | 6.3 | 73.7 | 18.1 | 0.0 | 0.2 | 0.0 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.0 | 5.9 | 85.3 | 8.8 | 0.0 | 0.0 | 0.0 | 0.0 |
Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 29
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. (NCT04492475)
Timeframe: Day 29
| Intervention | percentage of participants (Number) |
|---|
| Death at or before study visit | Hospitalized, on invasive mech. vent. or ECMO | Hospitalized, on non-invasive vent./high flow O2 | Hospitalized, requiring supplemental oxygen | Hospitalized, not on O2, requiring ongoing care | Hospitalized, not requiring O2, no longer req care | Not hospitalized, limit on activities/req home O2 | Not hospitalized, no limitations on activities |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 3.1 | 1.8 | 0.7 | 2.7 | 1.3 | 0.0 | 65.9 | 24.6 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 20.0 | 17.1 | 5.7 | 8.6 | 2.9 | 0.0 | 31.4 | 14.3 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 2.9 | 1.6 | 0.0 | 2.0 | 0.7 | 0.0 | 67.2 | 25.7 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 11.8 | 0.0 | 2.9 | 2.9 | 2.9 | 0.0 | 70.6 | 8.8 |
Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 22
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. (NCT04492475)
Timeframe: Day 22
| Intervention | percentage of participants (Number) |
|---|
| Death at or before study visit | Hospitalized, on invasive mech. vent. or ECMO | Hospitalized, on non-invasive vent./high flow O2 | Hospitalized, requiring supplemental oxygen | Hospitalized, not on O2, requiring ongoing care | Hospitalized, not requiring O2, no longer req care | Not hospitalized, limit on activities/req home O2 | Not hospitalized, no limitations on activities |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 2.2 | 1.8 | 0.7 | 4.0 | 1.8 | 0.0 | 48.0 | 41.6 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 17.1 | 22.9 | 8.6 | 8.6 | 0.0 | 0.0 | 22.9 | 20.0 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 2.5 | 1.6 | 0.2 | 4.2 | 1.6 | 0.2 | 49.6 | 40.2 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 11.8 | 0.0 | 2.9 | 8.8 | 2.9 | 0.0 | 55.9 | 17.6 |
Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 15
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. (NCT04492475)
Timeframe: Day 15
| Intervention | percentage of participants (Number) |
|---|
| Death at or before study visit | Hospitalized, on invasive mech. vent. or ECMO | Hospitalized, on non-invasive vent./high flow O2 | Hospitalized, requiring supplemental oxygen | Hospitalized, not on O2, requiring ongoing care | Hospitalized, not requiring O2, no longer req care | Not hospitalized, limit on activities/req home O2 | Not hospitalized, no limitations on activities |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 1.3 | 2.2 | 1.1 | 6.0 | 3.1 | 0.4 | 53.1 | 32.7 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 14.3 | 31.4 | 8.6 | 11.4 | 2.9 | 0.0 | 22.9 | 8.6 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 2.0 | 3.1 | 1.8 | 6.0 | 2.5 | 0.9 | 52.5 | 31.3 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 8.8 | 5.9 | 5.9 | 23.5 | 0.0 | 0.0 | 47.1 | 8.8 |
Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 11
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. (NCT04492475)
Timeframe: Day 11
| Intervention | percentage of participants (Number) |
|---|
| Death at or before study visit | Hospitalized, on invasive mech. vent. or ECMO | Hospitalized, on non-invasive vent./high flow O2 | Hospitalized, requiring supplemental oxygen | Hospitalized, not on O2, requiring ongoing care | Hospitalized, not requiring O2, no longer req care | Not hospitalized, limit on activities/req home O2 | Not hospitalized, no limitations on activities |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.9 | 3.1 | 2.9 | 10.0 | 5.8 | 0.9 | 73.9 | 2.7 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 8.6 | 42.9 | 14.3 | 5.7 | 2.9 | 2.9 | 22.9 | 0.0 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 1.6 | 2.7 | 2.9 | 12.7 | 5.8 | 0.4 | 70.5 | 3.3 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 5.9 | 11.8 | 14.7 | 26.5 | 2.9 | 0.0 | 38.2 | 0.0 |
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 for Participants With Baseline Ordinal Score 4 and 5
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Data was imputed using last observation carried forward or worst possible score based on hospitalization status (2 if not hospitalized, 7 if hospitalized) when there was a change in hospitalization status since last score. Deaths were imputed as an 8. (NCT04492475)
Timeframe: Day 15
| Intervention | percentage of participants (Number) |
|---|
| Death at or before study visit | Hospitalized, on invasive mech. vent. or ECMO | Hospitalized, on noninvasive vent./high flow O2 | Hospitalized, requiring supplemental oxygen | Hospitalized, not on O2, requiring ongoing care | Hospitalized, not requiring O2, no longer req care | Not hospitalized, limit on activities/req home O2 | Not hospitalized, no limitations on activities |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 1.3 | 2.2 | 1.1 | 6.0 | 3.1 | 0.4 | 53.1 | 32.7 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 2.0 | 3.1 | 1.8 | 6.0 | 2.5 | 0.9 | 52.5 | 31.3 |
Number of Participants With Discontinuation or Temporary Suspension of Study Product Administration
Discontinuation or temporary suspension of study product administration, including participants who died or were discharged, was evaluated by baseline ordinal scale category (categories 4 and 5 versus category 6). (NCT04492475)
Timeframe: Day 1 through Day 10
| Intervention | Participants (Count of Participants) |
|---|
| Remdesivir | Interferon Beta-1a/Placebo |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 400 | 337 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 25 | 13 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 382 | 341 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 22 | 19 |
Mean Change From Baseline in the Ordinal Scale
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. A positive change indicates a worsening and a negative change is an improvement. (NCT04492475)
Timeframe: Day 1, 3, 5, 8, 11, 15, 22, and 29
| Intervention | units on a scale (Mean) |
|---|
| Day 3 | Day 5 | Day 8 | Day 11 | Day 15 | Day 22 | Day 29 |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 0.1 | -0.1 | -0.2 | -0.4 | -2.5 | -2.8 | -2.9 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 0.1 | 0.3 | 0.3 | 0.1 | -0.8 | -1.3 | -1.5 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 0.1 | 0.0 | -0.1 | -0.4 | -2.5 | -2.8 | -3.0 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 0.0 | -0.1 | -0.4 | -0.6 | -2.3 | -2.9 | -3.2 |
Duration of Oxygen Use
Duration of oxygen use was measured in days among participants who were on oxygen in based, calculated in two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Including imputations for participants who died | Among participants who did not die |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 6 | 6 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 28 | 27.5 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 7.5 | 7 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 21.5 | 20.5 |
Duration of Non Invasive Ventilation or High Flow Oxygen Use
Duration of non invasive ventilation or high flow oxygen use was measured in days, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Including imputations for participants who died | Among participants who did not die |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 5 | 4 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 6 | 4 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 6 | 5 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 5.5 | 4 |
Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use
Duration of new ventilator or ECMO use was measured in days among participants who were not on a ventilator or ECMO at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die. (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Including imputations for participants who died | Among participants who did not die |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 28 | 14 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 23 | 19 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 26.5 | 14 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 28 | 13.5 |
Duration of New Oxygen Use
Duration of new oxygen use was measured in days among participants who were not on oxygen at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Including imputations for participants who died | Among participants who did not die |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 3 | 3 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 3 | 3 |
Duration of New Non-invasive Ventilation or High Flow Oxygen Use
Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Including imputations for participants who died | Among participants who did not die |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 5 | 4 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 6 | 5 |
Duration of Invasive Mechanical Ventilation
Duration of invasive ventilation was measured in days among participants who required invasive ventilation, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die (NCT04492475)
Timeframe: Day 1 through Day 29
| Intervention | Days (Median) |
|---|
| Including imputations for participants who died | Among participants who did not die |
|---|
| Remdesivir Plus Interferon Beta-1a in Ordinal Score 4 and 5 | 28 | 14 |
,| Remdesivir Plus Interferon Beta-1a in Ordinal Score 6 | 23 | 19 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 4 and 5 | 26.5 | 14 |
,| Remdesivir Plus Placebo in Baseline Ordinal Score 6 | 28 | 13.5 |
Mean Change From Baseline HBV DNA
(NCT04781647)
Timeframe: Baseline and at pre-specified time points up to 60 weeks
| Intervention | log10 IU/mL (Mean) |
|---|
| Week 1 | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | Week 32 | Week 36 | Week 40 | Week 44 | Week 48 |
|---|
| ABI-H0731 + ETV | -2.1 | -2.5 | -3.2 | -3.6 | -4.2 | -4.9 | -5.5 | -5.8 | -6.0 | -6.2 | -6.2 | -6.2 | -6.2 | -6.5 | -6.7 |
,| ABI-H0731 + ETV + Peg-IFNα | -2.1 | -2.6 | -2.9 | -3.6 | -4.1 | -4.4 | -5.2 | -5.6 | -6.0 | -6.3 | -6.2 | -6.2 | -6.0 | -5.8 | -5.9 |
,| ETV + Peg-IFNα | -2.2 | -2.7 | -3.4 | -4.0 | -4.5 | -5.1 | -5.6 | -6.1 | -6.5 | -6.7 | -6.7 | -6.9 | -6.7 | -6.6 | -6.8 |
Number of Participants With Premature Discontinuation of Treatment
(NCT04781647)
Timeframe: Up to 60 weeks
| Intervention | Participants (Count of Participants) |
|---|
| ABI-H0731 + ETV | 18 |
| ABI-H0731 + ETV + Peg-IFNα | 17 |
| ETV + Peg-IFNα | 11 |
Mean Change From Baseline in HBsAg
(NCT04781647)
Timeframe: Baseline and at pre-specified time points up to 60 weeks
| Intervention | log10 IU/mL (Mean) |
|---|
| Week 4 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | Week 32 | Week 36 | Week 40 | Week 44 | Week 48 |
|---|
| ABI-H0731 + ETV | -.2 | -.4 | -.5 | -.6 | -.6 | -.6 | -.7 | -.6 | -.6 | -.7 | -1.0 | -1.1 |
,| ABI-H0731 + ETV + Peg-IFNα | -.1 | -.4 | -.2 | -.2 | -.5 | -.5 | -.5 | -.4 | -.2 | -.1 | -.1 | -.1 |
,| ETV + Peg-IFNα | -.2 | -.5 | -.5 | -.6 | -.7 | -.7 | -.7 | -.8 | -.9 | -.9 | -1.0 | -1.1 |
Number of Participants With a Laboratory Abnormality
(NCT04781647)
Timeframe: Up to 60 weeks
| Intervention | Participants (Count of Participants) |
|---|
| ABI-H0731 + ETV | 19 |
| ABI-H0731 + ETV + Peg-IFNα | 16 |
| ETV + Peg-IFNα | 17 |
Mean Change From Baseline in HBV pgRNA
(NCT04781647)
Timeframe: Baseline and at pre-specified time points up to 60 weeks
| Intervention | log10 U/mL (Mean) |
|---|
| Week 1 | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | Week 32 | Week 36 | Week 40 | Week 44 | Week 48 |
|---|
| ABI-H0731 + ETV | -1.3 | -1.6 | -2.0 | -2.3 | -2.5 | -2.7 | -2.8 | -2.8 | -2.7 | -2.9 | -3.1 | -3.3 | -3.1 | -4.0 | -4.2 |
,| ABI-H0731 + ETV + Peg-IFNα | -1.5 | -1.9 | -2.2 | -2.6 | -2.7 | -3.0 | -2.9 | -3.0 | -3.3 | -3.0 | -3.0 | -2.9 | -2.5 | -3.3 | -2.4 |
,| ETV + Peg-IFNα | -.5 | -.6 | -.9 | -1.6 | -2.0 | -2.4 | -2.7 | -2.5 | -2.7 | -3.8 | -3.2 | -3.8 | -3.3 | -3.0 | -2.9 |
Plasma Concentration of ABI-H0731
(NCT04781647)
Timeframe: Predose on Day 1, Week 4, and Week 24 and at pre-specified time points postdose up to Week 24
| Intervention | ng/mL (Mean) |
|---|
| Day 1, Predose | Day 1, 2 to 4 hours postdose | Week 2, 30 min to 2 hours postdose | Week 4, predose | Week 8, 30 min to 2 hours postdose | Week 12, 30 min to 2 hours postdose | Week 16, 4 to 6 hours postdose | Week 20, 4 to 6 hours postdose | Week 24, predose | Week 24, 30 min to 2 hours postdose |
|---|
| ABI-H0731 + ETV | 0 | 852 | 2130 | 2070 | 2000 | 1920 | 2030 | 2210 | 2020 | 2070 |
,| ABI-H0731 + ETV + Peg-IFNα | 0 | 1240 | 1700 | 1390 | 1560 | 1650 | 2200 | 2090 | 1730 | 1580 |
Mean Change From Baseline in HBeAg
(NCT04781647)
Timeframe: Baseline and at pre-specified time points up to 60 weeks
| Intervention | log10 IU/mL (Mean) |
|---|
| Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | Week 32 | Week 36 | Week 40 | Week 44 | Week 48 |
|---|
| ABI-H0731 + ETV | -.6 | -.8 | -1.0 | -1.1 | -1.1 | -1.2 | -1.4 | -1.5 | -1.5 | -1.8 | -1.9 |
,| ABI-H0731 + ETV + Peg-IFNα | -.8 | -.8 | -.9 | -1.1 | -1.2 | -1.2 | -1.2 | -1.1 | -1.2 | -1.1 | -1.1 |
,| ETV + Peg-IFNα | -.9 | -1.1 | -1.2 | -1.3 | -1.3 | -1.4 | -1.5 | -1.7 | -1.8 | -1.9 | -2.1 |
Mean Change From Baseline in HBcrAg
(NCT04781647)
Timeframe: Baseline and at pre-specified time points up to 60 weeks
| Intervention | log10 kU/mL (Mean) |
|---|
| Week 4 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | Week 32 | Week 36 | Week 40 | Week 44 | Week 48 |
|---|
| ABI-H0731 + ETV | -.4 | -.6 | -.9 | -1.0 | -1.1 | -1.2 | -1.2 | -1.3 | -1.5 | -1.6 | -2.0 | -2.0 |
,| ABI-H0731 + ETV + Peg-IFNα | -.4 | -.8 | -.9 | -1.0 | -1.2 | -1.3 | -1.3 | -1.2 | -1.2 | -1.3 | -1.3 | -1.2 |
,| ETV + Peg-IFNα | -.3 | -.8 | -1.1 | -1.2 | -1.3 | -1.4 | -1.5 | -1.7 | -1.9 | -1.9 | -2.0 | -2.0 |
Plasma Concentration of ABI-H0731
(NCT04781647)
Timeframe: Predose on Day 1, Week 4, and Week 24 and at pre-specified time points postdose up to Week 24
| Intervention | ng/mL (Mean) |
|---|
| Week 24, predose | Week 24, 30 min to 2 hours postdose |
|---|
| ETV + Peg-IFNα | 0 | 374 |
Number of Participants With an Adverse Event
(NCT04781647)
Timeframe: Up to 60 weeks
| Intervention | Participants (Count of Participants) |
|---|
| ABI-H0731 + ETV | 14 |
| ABI-H0731 + ETV + Peg-IFNα | 17 |
| ETV + Peg-IFNα | 17 |