| Trial | Phase | Enrollment | Study Type | Start Date | Status |
|---|
| A 4-month, Open-label, Multi-center Study to Explore Tolerability and Safety and Health Outcomes of FTY720 in Patients With Relapsing Forms of Multiple Sclerosis[NCT01127750] | Phase 3 | 2,417 participants (Actual) | Interventional | 2010-05-31 | Completed |
| Long-term, Prospective,Multinational, Parallel-cohort Study Monitoring Safety in Patients With MS Newly Started With Fingolimod Once Daily or Treated With Another Approved Disease-modifying Therapy[NCT01442194] | | 3,076 participants (Actual) | Observational | 2011-08-01 | Completed |
| A 6-month, Randomized, Active Comparator, Open-label, Multi-Center Study to Evaluate Patient Outcomes, Safety and Tolerability of Fingolimod (FTY720) 0.5 mg/Day in Patients With Relapsing Remitting Multiple Sclerosis Who Are Candidates for MS Therapy Chan[NCT01317004] | Phase 4 | 61 participants (Actual) | Interventional | 2011-05-31 | Completed |
| A Randomized, Single Dose, Crossover, Bioequivalence Study of Fingolimod 0.5 mg Capsule (Asofarma S.A.I. y C., Argentina) Compared With Gilenya 0.5 mg Capsule (Novartis Pharmaceuticals, Australia Pty Ltd) in Fasting Healthy Subjects[NCT03757338] | Phase 1 | 33 participants (Actual) | Interventional | 2015-10-23 | Completed |
| A 6-month Multicenter, Single-arm, Open-label Study to Investigate Changes in Biomarkers After Initiation of Treatment With 0.5 mg Fingolimod (FTY720) in Patients With Relapsing-remitting Multiple Sclerosis[NCT01310166] | Phase 4 | 447 participants (Actual) | Interventional | 2011-02-28 | Completed |
| A Long Term, Multicenter, Non-interventional, Observational Study Monitoring Long-term Safety and Effectiveness of Fingolimod 0.5 mg in Patients With Multiple Sclerosis Who Have Participated in the Fingolimod Clinical Development Program[NCT01281657] | | 64 participants (Actual) | Observational | 2011-02-28 | 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 |
| A 32-week, Monocentric, Exploratory, Single Arm Study to Assess Immune Function and MRI Disease Activity in Patients With RRMS Transferred From Previous Treatment With Natalizumab to Gilenya® (Fingolimod)[NCT02325440] | Phase 4 | 15 participants (Anticipated) | Interventional | 2014-03-31 | Recruiting |
| Prevention of Paclitaxel-Associated Neuropathy With Fingolimod: a Pilot Trial[NCT03941743] | Phase 1 | 2 participants (Actual) | Interventional | 2019-12-12 | Completed |
| A Randomised Controlled Trial of Combinating an Immune Modulator Fingolimod With Alteplase Bridging With Mechanical Thrombectomy in Acute Ischemic Stroke[NCT04675762] | Phase 2 | 118 participants (Anticipated) | Interventional | 2021-01-15 | Recruiting |
| An Investigator-initiated, Multicenter, Phase IV, Open-label Study to Evaluate the Biological Basis for Disease Progression in Relapsing-remitting Multiple Sclerosis Patients Treated in Routine Practice With Gilenya for 2 Years[NCT02137707] | | 135 participants (Actual) | Observational | 2012-11-30 | Completed |
| A Phase 2, Randomized, Placebo-Controlled Study to Evaluate Fingolimod for the Abrogation of Interstitial Fibrosis and Tubular Atrophy Following Kidney Transplantation[NCT05285878] | Phase 2 | 20 participants (Anticipated) | Interventional | 2022-07-28 | Enrolling by invitation |
| Evaluating the Effect of Fingolimod With Fish Oil Compared to Fingolimod With Placebo on Tumor Necrosis Factor-α , Interleukin1b , Interleukin6, and Interferon-gamma in Patients With Relapsing-Remitting Multiple Sclerosis[NCT02939079] | Phase 2/Phase 3 | 50 participants (Actual) | Interventional | 2015-04-30 | Completed |
| A 12-Month, Prospective, Multicenter, Two-cohort, Nonrandomized, Open-label Study in Adult Patients With Relapsing Multiple Sclerosis (RMS), to Investigate Changes in Immune Phenotype Biomarkers After Treatment With 0.5mg Fingolimod [FLUENT][NCT03257358] | Phase 4 | 382 participants (Actual) | Interventional | 2017-09-19 | Completed |
| A Multicentric Randomized PRAGmatic Trial to Compare the Effectiveness of Fingolimod Versus Dimethyl-Fumarate on Patient Overall Disease Experience in Relapsing Remitting Multiple Sclerosis: Novel Data to Inform Decision-makers[NCT03345940] | Phase 4 | 55 participants (Actual) | Interventional | 2017-04-30 | Terminated(stopped due to termination of the study due to the slowness of the recruitment activity, according to the contract signed with the Sponsor) |
| A 24-month, Open-label, Prospective, Multicenter Interventional, Single-arm Study Assessing the Efficacy and Safety of Fingolimod (Gilenya) 0.5 mg in Relapsing Multiple Sclerosis (RMS) Patients in China[NCT04667949] | Phase 4 | 98 participants (Actual) | Interventional | 2021-02-20 | Active, not recruiting |
| Efficacy of Fingolimod in the Treatment of New Coronavirus Pneumonia (COVID-19)[NCT04280588] | Phase 2 | 0 participants (Actual) | Interventional | 2020-02-22 | Withdrawn(stopped due to No participants enrolled) |
| A Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5mg Fingolimod Administered Orally Once Daily Versus Placebo in Patients With Primary Progressive Multiple Sclerosis and An Open-label[NCT00731692] | Phase 3 | 970 participants (Actual) | Interventional | 2008-07-28 | Terminated(stopped due to The extension study was terminated early after the results of the core study showed the study did not meet primary endpoint; confirmed disability progression) |
| A Double-blind, Randomized, Placebo-controlled, Parallel, Time-lagged, Ascending, Multi-centre, Multiple-dose Study to Measure the Magnitude and Time Course of the Effect of FTY720 on FEV1 and Other Pulmonary Function Tests (FVC, FEF25-75%, and FEV1/FVC) [NCT00785083] | Phase 2 | 36 participants (Actual) | Interventional | 2008-09-30 | Completed |
| Assessing Induction of Type II (M2) Monocytes/Macrophages in Patients Receiving Gilenya.[NCT02225977] | | 125 participants (Actual) | Observational | 2013-07-31 | Completed |
| 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 |
| A Phase 1 Clinical Study to Assess Safety and Efficacy of Oral Fingolimod (FTY720) in Children With Rett Syndrome.[NCT02061137] | Phase 1/Phase 2 | 6 participants (Actual) | Interventional | 2013-08-31 | Completed |
| A Multicenter, Randomized, Open-Label Study to Assess the Impact of Natalizumab Versus Fingolimod on Central Nervous System Tissue Damage and Recovery in Active Relapsing-Remitting Multiple Sclerosis Subjects[NCT02342704] | Phase 4 | 111 participants (Actual) | Interventional | 2014-11-30 | Terminated(stopped due to Business Decision) |
| [NCT02193217] | Phase 1 | 81 participants (Actual) | Interventional | | Completed |
| Efficacy and Safety of Fingolimod in Minimal Invasive Treatment of Intracerebral Hemorrhage[NCT06087965] | Phase 1/Phase 2 | 40 participants (Anticipated) | Interventional | 2023-10-11 | Not yet recruiting |
| Combinating Fingolimod With Endovascular Treatment in Acute Ischemic Stroke[NCT04629872] | Phase 2 | 30 participants (Anticipated) | Interventional | 2020-11-12 | Recruiting |
| Fingolimod for Type 2 Diabetes Mellitus: a Pilot, Prospective, Randomized, and Open Label Single-center Study[NCT05307731] | Phase 4 | 40 participants (Anticipated) | Interventional | 2022-03-15 | Recruiting |
| A Phase III Multicenter, Randomized, Double-Blind, Double-Dummy Study To Evaluate Safety And Efficacy Of Ocrelizumab In Comparison With Fingolimod In Children And Adolescents With Relapsing-Remitting Multiple Sclerosis[NCT05123703] | Phase 3 | 233 participants (Anticipated) | Interventional | 2022-02-04 | Recruiting |
| Pregnancy Outcomes in Women Exposed to Diroximel Fumarate[NCT05688436] | | 1,178 participants (Anticipated) | Observational [Patient Registry] | 2021-09-24 | Recruiting |
| 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 |
| A 24-month, Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of Fingolimod 1.25 mg and 0.5 mg Administered Orally Once Daily Versus Placebo in Patients With Relapsing-remitting Multiple Scle[NCT00289978] | Phase 3 | 1,272 participants (Actual) | Interventional | 2006-01-31 | Completed |
| An Open-label, Single-dose, Parallel-group Study to Compare the Pharmacokinetics of FTY720 and Metabolites in Subjects With Severe Renal Impairment With That in Matched Healthy Control Subjects[NCT00731523] | Phase 1 | 18 participants (Actual) | Interventional | 2008-07-31 | Completed |
| An Extension of the 6-month, Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study Comparing Efficacy and Safety of FTY720 0.5 mg and 1.25 mg Administered Orally Once Daily in Patients With Relapsing Multiple Sclerosis[NCT00670449] | Phase 2 | 143 participants (Actual) | Interventional | 2008-04-30 | Completed |
| An Extension of the 24-month, Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing Efficacy and Safety of Fingolimod (FTY720) 1.25 mg and 0.5 mg Administered Orally Once Daily Versus Placebo in Patients With Relapsing-[NCT00662649] | Phase 3 | 920 participants (Actual) | Interventional | 2008-02-29 | Completed |
| A 4-month, Prospective, Open-label, Multi-center Phase IV Study to Assess Response to Fingolimod Initiation According to Coping Profile in Adult Patients With Highly Active Relapsing Remitting Multiple Sclerosis in France[NCT01420055] | Phase 4 | 189 participants (Actual) | Interventional | 2011-08-31 | Completed |
| A 6-month, Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study Comparing Efficacy and Safety of FTY720 0.5 mg and 1.25 mg Administered Orally Once Daily in Patients With Relapsing Multiple Sclerosis[NCT00537082] | Phase 2 | 171 participants (Actual) | Interventional | 2007-09-30 | Completed |
| 24-month Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5 mg and 1.25 mg Fingolimod (FTY720) Administered Orally Once Daily Versus Placebo in Patients With Relapsing-remitting Multipl[NCT00355134] | Phase 3 | 1,083 participants (Actual) | Interventional | 2006-06-30 | Completed |
| Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study Evaluating the Safety, Tolerability and Effect on MRI Lesion Parameters of FTY720 vs Placebo in Patients With Relapsing Multiple Sclerosis Including 18 Month Extension Phase[NCT00333138] | Phase 2 | 281 participants (Actual) | Interventional | 2003-05-31 | Completed |
| A 12 Month Study, With a 6-month, Double-blind, Randomized, Placebo-controlled, Multi-center Parallel- Groups, Treatment Phase Evaluating Efficacy and Safety of Fingolimod 0.5 mg and a 6-month, Open-label, Treatment Phase, in Chinese Patients With Relapsi[NCT01941004] | Phase 3 | 0 participants (Actual) | Interventional | 2014-06-30 | Withdrawn |
| A Two-year Extension to a One-year, Multicenter, Partially Blinded, Double Dummy, Randomized Study to Evaluate the Efficacy and Safety of FTY720 Combined With Reduced-dose or Full-dose Cyclosporine, USP [Modified] (Novartis Brand) and Corticosteroids Vers[NCT00239811] | Phase 3 | 684 participants | Interventional | 2004-04-30 | Completed |
| Efficacy and Safety of FTY720 for the Treatment of Acute Stroke[NCT02002390] | Phase 2 | 22 participants (Actual) | Interventional | 2012-10-31 | Completed |
| Treatment of Established Chemotherapy-Induced Neuropathy With Fingolimod: A Pilot Trial[NCT03943498] | Early Phase 1 | 2 participants (Actual) | Interventional | 2019-05-24 | Completed |
| A 3-month Blinded, Randomized, Multicenter, Placebo-controlled Study to Evaluate the Effect of Treatment With Fingolimod on the Immune Response Following Seasonal Influenza Vaccination and Tetanus Toxoid Booster Injection in Patients With Relapsing Forms [NCT01199861] | Phase 3 | 138 participants (Actual) | Interventional | 2010-08-31 | 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 |
| An Open Label Randomized, Single Dose, Two-way Crossover Bioequivalence Study to Determine the Bioequivalence of Fingolimod From Sphingomod 0.5 mg Hard Gelatin Capsules (Hikma Pharma, Egypt) Versus Gilenya 0.5 mg Hard Capsules (Novartis Pharma AG, Basle, [NCT04657744] | Phase 1 | 34 participants (Actual) | Interventional | 2020-08-10 | Completed |
| A 6-month, Randomized, Active Comparator, Open-label, Multi-Center Study to Evaluate Patient OutComes, Safety and Tolerability of Fingolimod (FTY720) 0.5 mg/Day in Patients With Relapsing Forms of Multiple Sclerosis Who Are Candidates for MS Therapy Chang[NCT01216072] | Phase 4 | 1,053 participants (Actual) | Interventional | 2010-08-31 | Completed |
| A 2-year Randomized, 3-arm, Double-blind, Non-inferiority Study Comparing the Efficacy and Safety of Ofatumumab and Siponimod Versus Fingolimod in Pediatric Patients With Multiple Sclerosis Followed by an Open-label Extension[NCT04926818] | Phase 3 | 180 participants (Anticipated) | Interventional | 2021-10-05 | Recruiting |
| A Randomised Controlled Trial of Combinating an Immune Modulator Fingolimod With Alteplase Bridging With Mechanical Thrombectomy in Acute Ischemic Stroke[NCT02956200] | Phase 2 | 0 participants (Actual) | Interventional | 2016-11-30 | Withdrawn |
| Impact of Fingolimod Adherence on Outcomes[NCT05141669] | | 694 participants (Actual) | Observational | 2020-05-18 | 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 |
| 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 |
| FINGORHYMS - Effects of Fingolimod on Heart Rhythm and Heart Rate Variability in Patients With Multiple Sclerosis[NCT03216915] | | 100 participants (Anticipated) | Observational | 2013-06-01 | Recruiting |
| A One-year, Multicenter, Partially Blinded, Double-dummy, Randomized Study to Evaluate the Efficacy and Safety of FTY720 Combined With Reduced-dose or Full-dose Cyclosporine, USP [Modified] (Novartis Brand) and Corticosteroids Versus Mycophenolate Mofetil[NCT00239785] | Phase 3 | 684 participants | Interventional | 2003-04-30 | Completed |
| A Two-year Extension to a One-year, Multicenter, Partially Blinded, Double-dummy, Randomized Study to Evaluate the Efficacy and Safety of FTY720 Combined With Reduced-dose or Full-dose Cyclosporine, USP [Modified] (Novartis Brand) and Corticosteroids Vers[NCT00239863] | Phase 3 | 684 participants | Interventional | 2004-05-31 | Completed |
| Two-year Extension of a One-year, Multicenter, Randomized, Partially-blinded Study of the Safety and Efficacy of FTY720 Combined With Corticosteroids and Full or Reduced-dose Cyclosporine, USP [Modified] (Novartis Brand) in de Novo Adult Renal Transplant [NCT00239902] | Phase 2 | 396 participants | Interventional | 2002-05-31 | Completed |
| Safety and Efficacy of FTY720 in Adult Patients Who Receive a Kidney Transplant[NCT00099801] | Phase 3 | 0 participants | Interventional | 2005-01-31 | Completed |
| A Randomized, Parallel Group, Double-blind, Placebo Controlled, 14 Days Multiple-dose Treatment to Assess the Pulmonary and Cardiac Pharmacodynamics of FTY720 (0.5 and 1.25 mg) in Healthy Volunteers[NCT00416845] | Phase 1 | 39 participants (Actual) | Interventional | 2006-10-31 | Completed |
| Efficacy and Safety of FTY720 in Patients Who Receive a Kidney Transplantation[NCT00098735] | Phase 3 | 140 participants | Interventional | 2004-04-30 | Completed |
| Safety and Efficacy of FTY720 in Adult Patients Who Receive a Kidney Transplant[NCT00099749] | Phase 2/Phase 3 | 255 participants | Interventional | 2003-11-30 | Completed |
| The Multi-National Gilenya Pregnancy Exposure Registry in Multiple Sclerosis[NCT01285479] | | 500 participants (Anticipated) | Observational [Patient Registry] | 2011-10-15 | Recruiting |
| A Single Arm, Open-label, Multicenter Study Evaluating the Long-term Safety and Tolerability of 0.5 mg Fingolimod (FTY720) Administered Orally Once Daily in Patients With Relapsing Forms of Multiple Sclerosis[NCT01201356] | Phase 3 | 4,125 participants (Actual) | Interventional | 2010-09-13 | Completed |
| An Open-Label, Balanced, Randomized, 2-Treatment, 2-Sequence, 2-Period, Single Dose, Crossover Oral Bioequivalence Study of Two Formulations of Fingolimod Capsules (3 x 0.5 mg) in Healthy Adult Human Subjects Under Fasting Conditions[NCT05145621] | Phase 1 | 26 participants (Actual) | Interventional | 2015-10-29 | Completed |
| Pharmacogenetic Investigation of Susceptibility to Liver Toxicity in Patients With Multiple Sclerosis Treated With Fingolimod[NCT05516303] | | 65 participants (Anticipated) | Observational | 2022-06-07 | Recruiting |
| Efficacy and Safety of FTY720 in Patients Who Receive a Kidney Transplant[NCT00099736] | Phase 3 | 696 participants (Actual) | Interventional | 2003-05-07 | Completed |
| Long-term Follow up of Patients With Relapsing-remitting Multiple Sclerosis Enrolled in the Multicenter, Single-arm, Open-label Biobank Study (CFTY720DDE01), to Investigate Changes in Biomarkers After 48 Months of Treatment With 0.5 mg Fingolimod (FTY720)[NCT02720107] | Phase 4 | 133 participants (Actual) | Interventional | 2016-05-12 | Completed |
| Safety and Effectiveness of Generic Fingolimod (Sphingomod®, Hikma) in Patients With Relapsing-Remitting Multiple Sclerosis in Egypt[NCT05423769] | | 30 participants (Anticipated) | Observational | 2022-01-19 | Active, not recruiting |
| A 24-month Extension of a One-year, Multicenter, Double Blinded Double Dummy, Randomized Study to Evaluate the Safety and Efficacy of Two Doses of FTY720 Combined With Full-dose Cyclosporine, USP [Modified] (Novartis Brand) and Steroids Versus Mycophenola[NCT00239798] | Phase 2 | 255 participants | Interventional | 2004-11-30 | Completed |
| A Two-year Extension to a One-year, Multicenter, Open-label, Randomised Study to Evaluate the Safety and Efficacy of FTY720 Combined With Tacrolimus and Steroids Versus Mycophenolate Mofetyl Combined With Tacrolimus and Steroids, in de Novo Adult Renal Tr[NCT00239876] | Phase 3 | 140 participants | Interventional | 2005-05-31 | Completed |
| Revascularization Pretreated With Fingolimod in Acute Stroke[NCT04718064] | | 20 participants (Anticipated) | Interventional | 2021-02-01 | Not yet recruiting |
| A 12-month, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of Fingolimod in the Treatment of Relapsing-remitting Multiple Sclerosis Patients With Neutralizing Antibodies to Interferon Beta[NCT01621269] | Phase 4 | 0 participants (Actual) | Interventional | 2013-06-30 | Withdrawn |
| Phase II/III Study to Investigate the Effects of Fingolimod Versus Interferon Beta-1b on Visual Recovery After Optic Neuritis[NCT01647880] | Phase 2/Phase 3 | 15 participants (Actual) | Interventional | 2013-07-31 | Terminated(stopped due to delayed recruitment) |
| A 48-week, Double-blind, Randomized, Multi-center, Parallel-group Study Comparing Structural Changes in the Retina and Evolution of Visual Function After Immediate Versus Delayed Treatment With Fingolimod in Patients With Acute Demyelinating Optic Neuriti[NCT01757691] | Phase 2 | 2 participants (Actual) | Interventional | 2013-08-31 | Terminated(stopped due to Discontinuation of this study was based on Novartis decision to discontinue development of fingolimod for the treatment of ADON) |
| The Long-term Effect of Fingolimod on Circulating Immunocompetent Mononuclear Cells in Patients With Multiple Sclerosis[NCT01755871] | Phase 4 | 8 participants (Actual) | Interventional | 2013-01-31 | Terminated(stopped due to lack of recruitment) |
| 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 |
| A 12-month, Prospective, Multi-center Post-authorization Commitment (PAC) Study Monitoring Safety in Adult Patients With Relapsing-remitting Multiple Sclerosis Newly Initiated on Gilenya (Fingolimod) in Taiwan (SPRING)[NCT04480853] | Phase 4 | 30 participants (Anticipated) | Interventional | 2020-10-12 | Recruiting |
| 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 |
| A Multicenter, Randomized, Active-controlled Study to Assess the Safety, Tolerability, and Efficacy of FTY720 in Patients With Acute, Noninfectious Intermediate, Posterior and Pan Uveitis[NCT01791192] | Phase 2 | 0 participants (Actual) | Interventional | 2013-11-30 | Withdrawn |
| Effects of Fingolimod (Gilenya®) on Cytokine and Chemokine Levels in Relapsing Remitting Multiple Sclerosis Patients[NCT02373098] | Phase 4 | 126 participants (Actual) | Interventional | 2015-03-31 | Completed |
| Phase IIa Double-Blind, Placebo-Controlled Study to Evaluate the Safety of Oral Fingolimod in Patients With Amyotrophic Lateral Sclerosis (ALS)[NCT01786174] | Phase 2 | 30 participants (Actual) | Interventional | 2013-08-31 | Completed |
| Safety and Efficacy of Fingolimod in Schizophrenia Patients Who Have Suboptimal Responses to Antipsychotic Drug Treatment[NCT01779700] | Phase 2 | 40 participants (Actual) | Interventional | 2013-01-31 | Completed |
| A 1-week, Open-label, Multi-center Study to Explore Conduction Abnormalities During First Dose Administration of Fingolimod in Patients With Relapsing-remitting Multiple Sclerosis[NCT01585298] | Phase 4 | 6,998 participants (Actual) | Interventional | 2012-04-29 | Completed |
| Effect of Fingolimod on Neurodegeneration, Brain Atrophy and Cognitive Impairment in Relapsing Remitting Multiple Sclerosis Patients[NCT02575365] | Phase 4 | 4 participants (Actual) | Interventional | 2016-02-16 | Terminated(stopped due to The trial was terminated due to low enrollment.) |
| A Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Fingolimod 0.5 mg Administered Orally Once Daily Versus Placebo in Patients With Chronic Inflammatory Demyelinating Polyradiculoneurop[NCT01625182] | Phase 3 | 106 participants (Actual) | Interventional | 2012-12-22 | Completed |
| A 32-week, Patient- and Rater-blinded, Randomized, Multi-center, Parallel-group Study to Evaluate Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis Transferred From Previous Treatment With Natalizumab to Fingolimod (FTY720[NCT01499667] | Phase 3 | 142 participants (Actual) | Interventional | 2011-09-30 | Terminated(stopped due to Based on recent publications, determination of natalizumub washout period was no longer relevant.) |
| A Multi-centre, Open-label, Non-randomised, Parallel Group Clinical Trial to Assess the Efficacy of Fingolimod in Naive Patients Versus Fingolimod in Patients Previously Treated With Interferons or Glatiramer Acetate, Based on the Presence of Relapses in [NCT01498887] | Phase 4 | 347 participants (Actual) | Interventional | 2011-12-24 | Completed |
| A 21-week, Multicenter, Open Label Study to Evaluate the Safety and Tolerability Profile of the Combination of a SSRI or SNRI Antidepressive Therapy With Oral Fingolimod in the Treatment of RRMS Patients With Mild to Moderate Depression[NCT01436643] | Phase 4 | 54 participants (Actual) | Interventional | 2011-11-30 | Terminated(stopped due to Due to slow enrollment the study was terminated early) |
| A Safety Study of Fingolimod With Radiation and Temozolomide in Newly Diagnosed High Grade Glioma[NCT02490930] | Early Phase 1 | 5 participants (Actual) | Interventional | 2015-07-31 | Completed |
| A 3-year Multi-center Study to Describe the Long Term Changes of Optical Coherence Tomography (OCT) Parameters in Patients Under Treatment With Gilenya®[NCT01705236] | Phase 4 | 87 participants (Actual) | Interventional | 2012-08-20 | Completed |
| A 12 -Month, Open-label, Multi-center Pilot Study to Explore the Health Outcomes of FTY720 in RRMS Patients Who Have Previously Been Treated With Other Disease Modifying Therapies (DMT)- Fine[NCT01578330] | Phase 4 | 42 participants (Actual) | Interventional | 2012-10-31 | Completed |
| A 4-month, Open-label, Multi-center Study to Explore the Safety and Tolerability of Fingolimod 0.5 mg in Patients With Relapsing-remitting Multiple Sclerosis[NCT01497262] | Phase 3 | 162 participants (Actual) | Interventional | 2012-02-29 | Completed |
| A 12-month, Prospective, Randomized, Active-controlled, Open-label Study to Evaluate the Patient Retention of Fingolimod vs. Approved First-line Disease Modifying Therapies in Adults With Relapsing Remitting Multiple Sclerosis (PREFERMS)[NCT01623596] | Phase 4 | 881 participants (Actual) | Interventional | 2012-06-08 | Completed |
| Funktionelle Evaluation Des Autonomen Nervensystems im Zusammenhang Mit Der Erstmaligen Einnahme Von 0,5mg Fingolimod (Gilenya) Bei Patienten Mit schubförmig Verlaufender Multipler Sklerose[NCT02048072] | Phase 4 | 33 participants (Actual) | Interventional | 2013-07-31 | Completed |
| STATURE: A Prospective Observational Study of the relationShip beTween Oral DMT bURden and adhErence in People With MS[NCT04676204] | | 323 participants (Anticipated) | Observational | 2020-09-25 | Enrolling by invitation |
| Fingolimod as a Treatment of Cerebral Edema After Intracerebral Hemorrhage[NCT04088630] | Early Phase 1 | 28 participants (Actual) | Interventional | 2020-08-07 | Active, not recruiting |
| Long-term, Open-label, Multicenter Study Assessing Long-term Cardiovascular Risks in Patients Treated With Fingolimod[NCT02232061] | Phase 4 | 6 participants (Actual) | Interventional | 2014-09-29 | Completed |
| A 12-month, Randomized, Rater- and Dose-blinded Study to Compare the Efficacy and Safety of Fingolimod 0.25 mg and 0.5 mg Administered Orally Once Daily With Glatiramer Acetate 20 mg Administered Subcutaneously Once Daily in Patients With Relapsing-remitt[NCT01633112] | Phase 3 | 1,064 participants (Actual) | Interventional | 2012-08-09 | Terminated(stopped due to slow recruitment) |
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] |
Change From Baseline in Patient-reported Activities of Daily Living (ADL)
The PRIMUS activity measure is a 15-item assessment used to evaluate patient-reported activities of daily living. The PRIMUS activities score was calculated summing the 15 items, after recoding the responses from 1 - 3 to 0 - 2. Therefore, the total score ranged from 0 - 3-, where high scores were indicative of greater function limitation. A negative change from baseline indicates improvement. (NCT01317004)
Timeframe: baseline, 6 months
| Intervention | score on a scale (Mean) |
|---|
| Fingolimod | 0.19 |
| Multiple Sclerosis Disease Modifying Treatment (MS DMT) | 0.15 |
Change From Baseline in Patient-reported Depression
The Beck Depression Inventory Fast Screen (BDI-FS) is a brief, multiple choice, self reported inventory designed to evaluate depression in patients with medical illness. The BDI-FS score was calculated summing the 7 items of the questionnaire. Each item ranged from 0 (not present) to 3 (severe). The total score ranges from 0-3 (minimal depression), 4-8 (mild depression), 9-12 (moderate depression) and 13-21 (severe depression). A negative change from baseline indicates improvement. (NCT01317004)
Timeframe: 6 months
| Intervention | score on a scale (Mean) |
|---|
| Fingolimod | -1.15 |
| Multiple Sclerosis Disease Modifying Treatment (MS DMT) | -0.12 |
Change From Baseline in Patient-reported Fatigue
The fatigue Severity Scale (FSS) is a 9-item scale used to assess fatigue. The FSS score was calculated summing the 9 items of the questionnaire and dividing by the number of non-missing items (each item is based on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree)). A negative change from baseline indicates improvement. (NCT01317004)
Timeframe: 6 months
| Intervention | score on a scale (Mean) |
|---|
| Fingolimod | -0.18 |
| Multiple Sclerosis Disease Modifying Treatment (MS DMT) | -0.32 |
Change From Baseline in Patient-reported Treatment Satisfaction
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. The lowest possible score (1 for each item and 3 for all 3 subscales) was subtracted from the composite score and divided by the greatest possible score range. The greatest range was (7-1) X 3 items = 18 for the effectiveness and convenience, and (5-1) x 3 items = 12 for global satisfaction. This provided a transformed score between 0 and 1 that was then multiplied by 100. A positive change from baseline indicates improvement. (NCT01317004)
Timeframe: baseline, 6 months
| Intervention | score on a scale (Mean) |
|---|
| Fingolimod | 19.57 |
| Multiple Sclerosis Disease Modifying Treatment (MS DMT) | 5.83 |
Change From Baseline in Patient-Reported Effectiveness and Convenience
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. The lowest possible score (1 for each item and 3 for all 3 subscales) was subtracted from the composite score and divided by the greatest possible score range. The greatest range was (7-1) X 3 items = 18 for the effectiveness and convenience, and (5-1) x 3 items = 12 for global satisfaction. This provided a transformed score between 0 and 1 that was then multiplied by 100. A positive change from baseline indicates improvement. (NCT01317004)
Timeframe: 6 months
| Intervention | score on a scale (Mean) |
|---|
| Effectiveness | Convenience |
|---|
| Fingolimod | 13.53 | 24.64 |
,| Multiple Sclerosis Disease Modifying Treatment (MS DMT) | -1.67 | 12.78 |
Change From Baseline in Patient-reported Health Related Quality of Life (QOL)
The SF-36v2 is a validated health-related quality of life instrument used in numerous disease states, including MS. It is a self-administered survey that measures 8 domains of health including: physical functioning, role limitations due to physical health, pain, general health, energy/fatigue, social functioning, role limitations due to emotional problems and emotional well-being. Additionally, two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). If half or more questions within a domain were answered, then a score was calculated for that domain. Otherwise, the patient score for that domain was set to missing. If the patient was missing any 1 of the 8 scale scores, then the physical and mental component scores were set to missing. An algorithm was used to create a score from 0 to 100 for each domain score and component score. A positive change from baseline indicates improvement. (NCT01317004)
Timeframe: 6 months
| Intervention | score on a scale (Mean) |
|---|
| Physical functioning (n=41,9) | Role limitations due to physical health (n=42,9) | Pain (n=45,9) | General health (n=44,8) | Energy/fatigue (n=43,9) | Social functioning (n=45,9) | Role limitations d/t emotional problems (n=45,9) | Emotional well-being (n=43,9) | PCS (n=40,8) | MCS (n=40,8) |
|---|
| Fingolimod | 1.71 | 7.14 | 6.56 | 4.52 | 2.33 | 7.78 | 7.04 | 2.51 | 4.52 | 5.88 |
,| Multiple Sclerosis Disease Modifying Treatment (MS DMT) | -1.11 | 5.56 | 14.44 | 6.25 | 6.48 | 6.94 | 3.70 | 4.89 | 7.83 | 7.28 |
Physician-reported Clinical Global Impression of Improvement (CGI-I)
The CGI-I is a rating scale allowing a physician-reported global evaluation of the subject's improvement over time. The Investigator assessed the subject's clinical change relative to the symptoms at baseline on the CGI-I, a seven-point scale, with rating as follows: 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse, 7=Very much worse. A lower score and a negative change from baseline indicate improvement. (NCT01317004)
Timeframe: 6 months
| Intervention | Percentage of participants (Number) |
|---|
| Much improved | Minimally improved | No change | Minimally worse |
|---|
| Fingolimod | 13.64 | 36.36 | 47.73 | 2.27 |
,| Multiple Sclerosis Disease Modifying Treatment (MS DMT) | 11.11 | 11.11 | 66.67 | 11.11 |
Serum Level of IFN-gamma
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: 1 year after intervention
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 5.92 |
| Fingolimod and Placebo | 5.99 |
Serum Level of IFN-gamma
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: 6 months after intervention
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 5.71 |
| Fingolimod and Placebo | 6.37 |
Serum Level of IFN-gamma
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: Baseline
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 6.38 |
| Fingolimod and Placebo | 6.98 |
Serum Level of IL1b
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: 1 year after intervention
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 13.17 |
| Fingolimod and Placebo | 13.15 |
Serum Level of IL1b
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: 6 months after intervention
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 13.61 |
| Fingolimod and Placebo | 13.47 |
Serum Level of IL1b
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: Baseline
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 13.76 |
| Fingolimod and Placebo | 14 |
Serum Level of IL6
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: 1 year after intervention
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 6.17 |
| Fingolimod and Placebo | 6.05 |
Serum Level of IL6
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: 6 months after intervention
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 6.65 |
| Fingolimod and Placebo | 6.17 |
Serum Level of IL6
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: Baseline
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 6.19 |
| Fingolimod and Placebo | 6.33 |
Serum Level of TNF-α
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: 1 year after intervention
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 21.20 |
| Fingolimod and Placebo | 16.47 |
Serum Level of TNF-α
5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: 6 months after intervention
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 28.03 |
| Fingolimod and Placebo | 17.18 |
Serum Level of TNF-α
5 cc of venous blood is taken from patients and are kept in test tubes without ethylenediaminetetraacetic acid (EDTA). Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. (NCT02939079)
Timeframe: Baseline
| Intervention | Pg/ml (Mean) |
|---|
| Fingolimod and Fish Oil | 37.16 |
| Fingolimod and Placebo | 28.79 |
Change From Baseline for New Gd-Enhancing T1 Lesion Count
(NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | number of lesions (Mean) |
|---|
| Baseline (BL) n=125,147 | Month 12 n=33,28 | Change from BL to Month 12 n=33,28 |
|---|
| Cohort 1 | 0.4 | 0.1 | -0.2 |
,| Cohort 2 | 0.2 | 0.2 | 0.2 |
Change From Baseline in Patient Determined Disease Steps (PDDS)
PDDS scoring ranges 0 to 8. 0 = Normal; 1 = Mild disability; 2 = Moderate disability; 3 = Gait disability; 4 = Early cane; 5 = Late cane; 6 = Bilateral support; 7 = Wheelchair/scooter; 8 = Bedridden. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | scores (Mean) |
|---|
| Baseline (BL) n=163,217 | Month 12 n=103,188 | Change from BL to Month 12 n=103,188 |
|---|
| Cohort 1 | 1.7 | 1.8 | -0.1 |
,| Cohort 2 | 1.8 | 1.8 | -0.0 |
Change From Baseline in T2 Lesion Burden
(NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | number of lesions (Mean) |
|---|
| Baseline (BL) n=91,84 | Month 12 n=21,17 | Change from BL to Month 12 n=21,17 |
|---|
| Cohort 1 | 8.1 | 6.5 | -0.8 |
,| Cohort 2 | 9.7 | 13.1 | 3.2 |
Change From Baseline to Month 12 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Change from BL to Month 12 n=83,150 |
|---|
| Cohort 1 | 374.6 | -356.8 |
,| Cohort 2 | 16.3 | 3.9 |
Change From Baseline to Month 12 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Change from BL to Month 12 n=83,150 |
|---|
| Cohort 1 | 74.3 | -50.4 |
,| Cohort 2 | 22.8 | -3.3 |
Change From Baseline to Month 12 in CD4+ Naive T Cells (CCR7+CD45RA+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Change from BL to Month 12 n=82,150 |
|---|
| Cohort 1 | 404.4 | -376.3 |
,| Cohort 2 | 3.4 | -0.8 |
Change From Baseline to Month 12 in CD4+ Th1 Cells (CXCR3+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=148,211 | Change from BL to Month 12 n=88,175 |
|---|
| Cohort 1 | 53.8 | -42.3 |
,| Cohort 2 | 11.1 | -2.1 |
Change From Baseline to Month 12 in CD4+ Th17 Cells (CCR6+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=148,212 | Change from BL to Month 12 n=88,175 |
|---|
| Cohort 1 | 55.5 | -52.1 |
,| Cohort 2 | 2.4 | 0.5 |
Change From Baseline to Month 12 in CD4+ Th2 Cells (CCR4+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=148,212 | Change from BL to Month 12 |
|---|
| Cohort 1 | 35.9 | -36.3 |
,| Cohort 2 | 1.1 | 0.4 |
Change From Baseline to Month 12 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Change from BL to Month 12 n=83,150 |
|---|
| Cohort 1 | 93.1 | -86.5 |
,| Cohort 2 | 5.6 | 0.0 |
Change From Baseline to Month 12 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Change from BL to Month 12 n=83,150 |
|---|
| Cohort 1 | 108.2 | -55.9 |
,| Cohort 2 | 63.8 | -15.9 |
Change From Baseline to Month 12 in CD8+ Naive T Cells (CCR7+CD45RA+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Change from BL to Month 12 n=83,150 |
|---|
| Cohort 1 | 150.9 | -126.3 |
,| Cohort 2 | 1.8 | 0.6 |
Change From Baseline to Month 12 in Memory B Lymphocytes (CD19+CD27+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=144,212 | Change from BL to Month 12 n=82,174 |
|---|
| Cohort 1 | 61.8 | -46.4 |
,| Cohort 2 | 3.3 | 1.4 |
Change From Baseline to Month 12 in Monocytes (CD14+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=150,197 | Change from BL to Month 12 n=86,164 |
|---|
| Cohort 1 | 329.6 | 57.1 |
,| Cohort 2 | 251.7 | 112.4 |
Change From Baseline to Month 12 in Naive B Lymphocytes (CD19+CD27-)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=144,212 | Change from BL to Month 12 n=82,174 |
|---|
| Cohort 1 | 201.11 | -177.0 |
,| Cohort 2 | 18.1 | -0.5 |
Change From Baseline to Month 12 in Neutrophils (CD16+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=149,197 | Change from BL to Month 12 n=87, 164 |
|---|
| Cohort 1 | 4041.4 | -815.9 |
,| Cohort 2 | 3717.9 | -345.0 |
Change From Baseline to Month 12 in NK Cells (CD56+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=149,197 | Change from BL to Month 12 n=87,164 |
|---|
| Cohort 1 | 166.4 | -32.6 |
,| Cohort 2 | 181.0 | -28.9 |
Change From Baseline to Month 12 in Regulatory B Lymphocytes (CD19+CD24+CD38+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=144,212 | Change from BL to Month 12 n=82,174 |
|---|
| Cohort 1 | 12.3 | -7.7 |
,| Cohort 2 | 5.3 | 0.8 |
Change From Baseline to Month 12 in Total CD19+ Absolute Cell Count
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=151,213 | Change from BL to Month 12 n=88,176 |
|---|
| Cohort 1 | 259.7 | -218.9 |
,| Cohort 2 | 21.4 | 1.0 |
Change From Baseline to Month 12 in Total CD19+ Differential Cell Count (%)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=152,213 | Change from BL to Month 12 n=89,176 |
|---|
| Cohort 1 | 13.97 | -8.86 |
,| Cohort 2 | 4.81 | 0.20 |
Change From Baseline to Month 12 in Total CD4+ Absolute Cell Count
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=156,213 | Change from BL to Month 12 n=94,176 |
|---|
| Cohort 1 | 936.3 | -844.9 |
,| Cohort 2 | 64.4 | 0.7 |
Change From Baseline to Month 12 in Total CD4+ Differential Cell Count (%)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=157,213 | Change from BL to Month 12 n=95,176 |
|---|
| Cohort 1 | 49.40 | -37.90 |
,| Cohort 2 | 11.95 | 0.70 |
Change From Baseline to Month 12 in Total CD8+ Absolute Cell Count
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=156,213 | Change from BL to Month 12 n=94,176 |
|---|
| Cohort 1 | 419.9 | -265.1 |
,| Cohort 2 | 124.6 | -11.6 |
Change From Baseline to Month 12 in Total CD8+ Differential Cell Counts (%)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=157,213 | Change from BL to Month 12 n=95,176 |
|---|
| Cohort 1 | 21.86 | 4.33 |
,| Cohort 2 | 25.25 | 0.34 |
Change From Baseline to Month 6 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Month 6 n=97,156 | Change from BL to Month 6, n=97,156 |
|---|
| Cohort 1 | 374.6 | 19.6 | -368.9 |
,| Cohort 2 | 16.3 | 18.3 | 1.1 |
Change From Baseline to Month 6 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Month 6, n=97,156 | Change from BL to Month 6 n=97,156 |
|---|
| Cohort 1 | 74.3 | 18.2 | -51.5 |
,| Cohort 2 | 22.8 | 21.7 | -2.0 |
Change From Baseline to Month 6 in CD4+ Naive T Cells (CCR7+ CD45RA+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Month 6 n=97,156 | Change from BL to Month 6, n=97,156 |
|---|
| Cohort 1 | 404.4 | 7.6 | -411.4 |
,| Cohort 2 | 3.4 | 4.8 | 0.8 |
Change From Baseline to Month 6 in CD4+ Th1 Cells (CXCR3+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=148,211 | Month 6 n=104,180 | Change from BL to Month 6 n=104,180 |
|---|
| Cohort 1 | 53.8 | 7.6 | -43.6 |
,| Cohort 2 | 11.1 | 11.7 | -0.7 |
Change From Baseline to Month 6 in CD4+ Th17 Cells (CCR6+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=148,212 | Month 6 n=104,181 | Change from BL to Month 6 n=104,181 |
|---|
| Cohort 1 | 55.5 | 3.1 | -53.2 |
,| Cohort 2 | 2.4 | 2.8 | 0.5 |
Change From Baseline to Month 6 in CD4+ Th2 Cells (CCR4+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=148,212 | Month 6 n=104,181 | Change from BL to Month 6 n=104,181 |
|---|
| Cohort 1 | 35.9 | 1.7 | -36.1 |
,| Cohort 2 | 1.1 | 1.6 | 0.5 |
Change From Baseline to Month 6 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Month 6 n=97,156 | Change from BL to Month 6 n=97,156 |
|---|
| Cohort 1 | 93.1 | 5.9 | -85.2 |
,| Cohort 2 | 5.6 | 6.1 | 0.0 |
Change From Baseline to Month 6 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Month 6 n=97,156 | Change from BL to Month 6 n=97,156 |
|---|
| Cohort 1 | 108.2 | 55.4 | -40.6 |
,| Cohort 2 | 63.8 | 52.6 | -12.5 |
Change From Baseline to Month 6 in CD8+ Naive T Cells (CCR7+CD45RA+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=147,188 | Month 6 n=97,156 | Change from BL to Month 6 n=97,156 |
|---|
| Cohort 1 | 150.9 | 4.2 | -139.3 |
,| Cohort 2 | 1.8 | 3.3 | 1.2 |
Change From Baseline to Month 6 in Memory B Lymphocytes (CD19+CD27+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=144,212 | Month 6 n=101,176 | Change from BL to Month 6 n=101,176 |
|---|
| Cohort 1 | 61.8 | 3.8 | -55.1 |
,| Cohort 2 | 3.3 | 4.0 | 0.3 |
Change From Baseline to Month 6 in Monocytes (CD14+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=150,197 | Month 6 n=105,166 | Change from BL to Month 6 n=105,166 |
|---|
| Cohort 1 | 329.6 | 384.7 | 66.1 |
,| Cohort 2 | 251.7 | 379.2 | 123.1 |
Change From Baseline to Month 6 in Naive B Lymphocytes (CD19+CD27-)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=144,212 | Month 6 n=101,176 | Change from BL to Month 6 n=101,176 |
|---|
| Cohort 1 | 201.1 | 15.0 | -181.4 |
,| Cohort 2 | 18.1 | 17.8 | -0.2 |
Change From Baseline to Month 6 in Neutrophils (CD16+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=149,197 | Month 6 n=105,166 | Change from BL to Month 6 n=105,166 |
|---|
| Cohort 1 | 4041.4 | 3505.4 | -586.0 |
,| Cohort 2 | 3717.9 | 3312.6 | -439.6 |
Change From Baseline to Month 6 in NK Cells (CD56+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=149,197 | Month 6 n=105,166 | Change from BL to Month 6 n=105,166 |
|---|
| Cohort 1 | 166.4 | 133.6 | -29.4 |
,| Cohort 2 | 181.0 | 154.5 | -28.0 |
Change From Baseline to Month 6 in Regulatory B Lymphocytes (CD19+CD24+CD38+)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=144,212 | Month 6 n=101,176 | Change from BL to Month 6 n=101,176 |
|---|
| Cohort 1 | 12.3 | 4.8 | -7.4 |
,| Cohort 2 | 5.3 | 6.1 | 0.9 |
Change From Baseline to Month 6 in Total CD19+ Absolute Cell Count
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=151,213 | Month 6 n=106,179 | Change from BL to Month 6 n=106,179 |
|---|
| Cohort 1 | 259.7 | 19.5 | -231.3 |
,| Cohort 2 | 21.4 | 21.8 | 0.1 |
Change From Baseline to Month 6 in Total CD19+ Differential Cell Count (%)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=152,213 | Month 6 n=107,180 | Change from BL to Month 6 n=107,180 |
|---|
| Cohort 1 | 13.97 | 5.38 | -8.53 |
,| Cohort 2 | 4.81 | 4.83 | 0.23 |
Change From Baseline to Month 6 in Total CD4+ Absolute Cell Count
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=156,213 | Month 6 n=110,182 | Change from BL to Month 6 n=110,182 |
|---|
| Cohort 1 | 936.3 | 53.4 | -884.1 |
,| Cohort 2 | 64.4 | 71.3 | 1.4 |
Change From Baseline to Month 6 in Total CD4+ Differential Cell Count
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=157,213 | Month 6 n=111,183 | Change from BL to Month 6 n=111,183 |
|---|
| Cohort 1 | 49.40 | 11.08 | -39.09 |
,| Cohort 2 | 11.95 | 12.82 | 0.32 |
Change From Baseline to Month 6 in Total CD8+ Absolute Cell Count
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=156,213 | Month 6 n=110,182 | Change from BL to Month 6 n=110,182 |
|---|
| Cohort 1 | 419.9 | 120.1 | -266.2 |
,| Cohort 2 | 124.6 | 116.8 | -13.5 |
Change From Baseline to Month 6 in Total CD8+ Differential Cell Counts (%)
Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected. (NCT03257358)
Timeframe: Baseline to Month 6
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=157,213 | Month 6 n=111,183 | Change from BL to Month 6 |
|---|
| Cohort 1 | 21.86 | 25.33 | 4.63 |
,| Cohort 2 | 25.25 | 24.99 | -0.39 |
Change From Baseline to Months 6 and 12 in the Anti-JCV Antibody Index (Index/Value)
(NCT03257358)
Timeframe: Baseline to Month 6 and 12
| Intervention | cells/uL (Mean) |
|---|
| Baseline (BL) n=159,215 | Change from BL to Month 6 n=116,195 | Change from BL to Month 12 n=100,180 |
|---|
| Cohort 1 | 1.273 | 0.038 | 0.040 |
,| Cohort 2 | 1.391 | 0.045 | 0.145 |
Multiple Sclerosis (MS) Relapses During Treatment
A relapse is 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 demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5°C) or infection. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | relapses (Number) |
|---|
| Number of patients with relapses | Total number of relapses | Relapses not requiring steroid use | Relapses requiring steroid use | Mild relapse | Moderate relapse | Severe relapse |
|---|
| Cohort 1 | 11 | 12 | 5 | 7 | 5 | 6 | 1 |
,| Cohort 2 | 13 | 13 | 5 | 8 | 8 | 5 | 0 |
Number of Participants Who Received Steroid Treatment for MS Relapses During Treatment
A relapse is 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 demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5°C) or infection. (NCT03257358)
Timeframe: Baseline to Month 12
| Intervention | Participants (Count of Participants) |
|---|
| Patients with ≥ 1 relapses | Patients with relapse who received ≥ 1 steroid | Corticosteroids for systemic use | Methylprednisolone sodium succinate | Methylprednisolone | Prednisone |
|---|
| Cohort 1 | 11 | 7 | 7 | 4 | 3 | 0 |
,| Cohort 2 | 13 | 8 | 8 | 4 | 2 | 3 |
Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D Score)
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT00731692)
Timeframe: Baseline, 36 months
| Intervention | Score on a scale (Mean) |
|---|
| FTY720 1.25 mg to 0.5 mg | -0.0332 |
| FTY720 0.5 mg to 0.5 mg | -0.0475 |
| Placebo | -0.0539 |
Change From Baseline in Multiple Sclerosis Walking Scale (MSWS-12 Score)
The Multiple Sclerosis Walking Scaleis a patient reported measure of walking quality (Hobart et al 2003), consisting of 12 items asking patients to rate the impact of MS upon their walking ability. Responses were captured on a 3-point scale ranging from 1 (Not at all) to 3 (A lot) for items 1 to 3 and on a 5-point scale ranging from 1 (not limited) to 5 (extremely) for items 4 to 12. All 12 item scores were summed to obtain a total score ranging from 12 (good) to 54 (poor) which is the MSWS-12 scale score. The total score was transformed to a 0 to 100 scale score. The MSWS-12 scale score will be transformed to a 0-100 scale score before any summaries or statistical analyses are performed. The transformed score is obtained by subtracting 12 and divided by 42 and multiplying by 100 (i.e., transformed scale score = (raw scale score- 12)/42*100). (NCT00731692)
Timeframe: Baseline, 36 months
| Intervention | Score on a scale (Mean) |
|---|
| FTY720 1.25 mg to 0.5 mg | 6.4444 |
| FTY720 0.5 mg to 0.5 mg | 5.5616 |
| Placebo | 9.5899 |
Change From Baseline in PRIMUS-Activities
The activities subscale of PRIMUS contains 15 items and each item is given a score of 0 (able to do on own without difficulties), 1 (able to do on own with difficulties), or 2 (unable to do on own). All 15 items were summed to obtain a total score ranging from 0 (good) to 30 (poor). (NCT00731692)
Timeframe: Baseline, 36 months
| Intervention | Score on a scale (Mean) |
|---|
| FTY720 1.25 mg to 0.5 mg | 3.5504 |
| FTY720 0.5 mg to 0.5 mg | 2.6324 |
| Placebo | 2.8830 |
Change From Baseline in the Patient Reported Indices in Multiple Sclerosis (PRIMUS-QoL Score)
The quality of life scale contains 22 items. Each item will be given a score of 1 or 0. A score of 1 (or 0) indicates the presence (or absence) of the symptom or adverse quality of life. All 22 item scores will be summed to obtain a total score ranging from 0 (good) to 22 (poor), which is the PRIMUS QoL scale score (NCT00731692)
Timeframe: Baseline, 36 months
| Intervention | Score on a scale (Mean) |
|---|
| FTY720 1.25 mg to 0.5 mg | 0.2424 |
| FTY720 0.5 mg to 0.5 mg | 0.5921 |
| Placebo | 0.9597 |
Change From Baseline in Unidimensional Fatigue Impact (U-FIS) Score
Unidimensional Fatigue Impact Scale (U-FIS), contains 22 patient-reported items that assess the impact of fatigue on cognitive, physical, and psychosocial functioning. Responses formed a single unidimensional scale measuring fatigue impact. The U-FIS was calculated and analyzed according to the U-FIS scoring manual. The U-FIS scale contains 22 items with 5 possible outcomes for each item. Two response categories (about half the time and a lot of the time) were combined into 1 category to obtain 4 possible outcomes: 0 (never), 1 (a little of the time), 2 (about half the time/a lot of the time), and 3 (all the time). The 22 condensed item scores were summed to obtain a total score ranging from 0 (no fatigue) to 66 (severe fatigue impact). (NCT00731692)
Timeframe: Baseline, 36 months
| Intervention | Score on a scale (Mean) |
|---|
| FTY720 1.25 mg to 0.5 mg | 1.3197 |
| FTY720 0.5 mg to 0.5 mg | 2.8451 |
| Placebo | 3.1394 |
Change in MSFC Z-score and Subscale Scores From Baseline to Month 36
The Multiple Sclerosis Functional Composite (MSFC) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation (Timed 25-Foot Walk), arm function (9-Hole Peg Test), and cognitive function (Paced Auditory Serial Addition Test). The overall MSFC z-score as an average of the three standardized scores derived using baseline data pooled over each treatment arm as reference population. Higher scores reflect better neurological function and a positive change from Baseline indicates improvement. (NCT00731692)
Timeframe: Baseline to Month 36
| Intervention | Z-scores (Mean) |
|---|
| FTY720 0.5 mg | -0.189 |
| Placebo | -0.212 |
Kaplan Meier Estimate -Percentage of Participants With 3- Month Confirmed Disability Progression Based on 25' TWT.
The 25' TWT is a quantitative measure of lower extremity function designed and validated for evaluation of MS patients. N= Total number of patients included in the analysis (NCT00731692)
Timeframe: up to 36 months after the last patient was randomized
| Intervention | Percentage of Participants (Number) |
|---|
| FTY720 0.5 mg to 0.5 mg | 54.8 |
| Placebo | 56.7 |
Kaplan Meier Estimate -Percentage of Participants With 3- Month Confirmed Disability Progression Based on 9-HPT.
The 9-HPT is a quantitative measure of upper extremity (arm and hand) function designed and validated for evaluation of MS patients. N= Total number of patients included in the analysis (NCT00731692)
Timeframe: up to 36 months after the last patient was randomized
| Intervention | Percentge of Participants (Number) |
|---|
| FTY720 0.5 mg to 0.5 mg | 25.0 |
| Placebo | 24.9 |
Kaplan-Meier Estimate of the Risk of 3- Month Confirmed Disability Progression Based on Expanded Disability Status Scale (EDSS)
The Expanded Disability Status Scale (EDSS) is a scale for assessing neurologic impairment in MS (Kurtzke 1983) and includes a series of scores in each of 8 functional systems and the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Fatigue is not included in the Cerebral score of the EDSS. The score ranges from 0 (normal) to 10 (death due to MS) (NCT00731692)
Timeframe: up to 36 months after the last patient was randomized
| Intervention | Percentage of Participants (Number) |
|---|
| FTY720 0.5 mg to 0.5 mg | 54.3 |
| Placebo | 58.7 |
Kaplan-Meier Estimate of the Risk of 3-month Confirmed Disability Progression Based on Composite Endpoint
3-month sustained increase from Baseline in EDSS (at least 1 point increase from Baseline for patients with a Baseline value of 5 or less or at least 0.5 point increase from Baseline for patients with a Baseline value of 5.5 or more) or 3-month sustained increase of at least 20% from BL in the time taken to complete the timed 25-foot walk test (25' TWT); or 3-month sustained increase of at least 20% from BL in the time taken to complete the 9-HPT. The 25' TWT is a quantitative measure of lower extremity function. The EDSS is a scale assessing neurologic impairment, including a series of scores in each of 8 functional systems: Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. The score ranges from 0 (normal) to 10 (death due to MS)). The 9-hole peg test (9-HPT) is a quantitative measure of upper extremity (arm and hand) function. (NCT00731692)
Timeframe: up to 36 months after the last patient was randomized
| Intervention | Percentage of Participants (Number) |
|---|
| FTY720 0.5 mg to 0.5 mg | 77.2 |
| Placebo | 80.3 |
Number of Gd-enhancing Lesions at Month 36
Inflammatory disease, as measured by number of T1 Gd-enhancing lesions, was assessed by MRI scanning of the brain and full spinal cord. N= Total number of patients included in the analysis (NCT00731692)
Timeframe: Baseline to 36 months
| Intervention | Gd-enhanced lesions per patient per scan (Least Squares Mean) |
|---|
| FTY720 0.5 mg to 0.5 mg | 0.05 |
| Placebo | 0.21 |
Number of New/Enlarging T2 Lesions Per Year Measured From Baseline to Month 36
Inflammatory disease, as measured by number of new or newly-enlarging T2 lesions, was assessed by Magnetic resonance Imaging (MRI) scanning of the brain and full spinal cord. N= Total number of patients included in the analysis (NCT00731692)
Timeframe: Baseline to 36 months
| Intervention | T2 Lesions per year (Least Squares Mean) |
|---|
| FTY720 0.5 mg to 0.5 mg | 0.13 |
| Placebo | 0.50 |
Percent Change From Baseline in Brain Volume at Month 36
The percent change from Baseline in brain volume was analyzed using a random coefficients model. The model included: 1) fixed effects: treatment and region and 2) continuous covariates: time, number of Gd enhancing lesions at Baseline, Baseline T2 volume, and normalized brain volume at Baseline. Time as a continuous covariate allowed for the estimation of different slopes and intercepts among treatment groups. (NCT00731692)
Timeframe: Baseline to month 36
| Intervention | Percent Change (Least Squares Mean) |
|---|
| FTY720 0.5 mg to 0.5 mg | -1.49 |
| Placebo | -1.53 |
Percent Change in Total T2 Lesion Volume From Baseline to Month 36
Inflammatory disease as measured by percent change in total T2 lesion volume (mm3) was assessed by MRI. N= Total number of patients included in the analysis (NCT00731692)
Timeframe: Baseline to month 36
| Intervention | Percent Change (Mean) |
|---|
| FTY720 0.5 mg to 0.5 mg | -9.2 |
| Placebo | 8.9 |
Blood Concentrations of Fingolimod and Fingolimod-phosphate
"Concentrations of fingolimod and fingolimod-phosphate in whole blood were determined by validated liquid chromatography methods with tandem mass spectrometry. The lower limits of quantification were 0.08 ng/ml for fingolimod and 0.1 ng/ml for fingolimod-phosphate.~Venous blood samples were collected for the analysis." (NCT00731692)
Timeframe: Month 3 up to 36 months
| Intervention | ng/ml (Mean) |
|---|
| Month 3 Fingolimod (n=64, 179) | Month 12 Fingolimod (n=23, 161) | Month 18 Fingolimod (n=71,155) | Month 24 Fingolimod (n=67, 160) | Month 30 Fingolimod (n=62, 158) | Month 36 Fingolimod (n=55, 118) | End of treatment Fingolimod (n=32, 115) | Month 3 Fingolimod-Phosphate (n=64, 179) | Month 12 Fingolimod-Phosphate (n=23, 161) | Month 18 Fingolimod-Phosphate (n=71,155) | Month 24 Fingolimod-Phosphate (n=67, 160) | Month 30 Fingolimod-Phosphate (n=62, 158) | Month 36 Fingolimod-Phosphate (n=55, 118) | End of treatment Fingolimod-Phosphate (n=32, 115 |
|---|
| FTY720 0.5 mg to 0.5 mg | 2.58 | 2.55 | 2.59 | 2.64 | 2.60 | 2.63 | 2.57 | 1.40 | 1.43 | 1.41 | 1.44 | 1.48 | 1.51 | 1.50 |
,| FTY720 1.25 mg to 0.5 mg | 6.04 | 6.24 | NA | NA | NA | NA | NA | 3.20 | 3.21 | NA | NA | NA | NA | NA |
,| FTY720 1.25mg to 0.5 mg | NA | 2.87 | 2.44 | 2.41 | 2.52 | 2.44 | 2.02 | NA | 1.54 | 1.34 | 1.35 | 1.32 | 1.32 | 1.19 |
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 |
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 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 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 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 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 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 - 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 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 |
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 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 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 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 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 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 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 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 |
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 |
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 Baseline in SDMT at Week 52
The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution. (NCT02342704)
Timeframe: Baseline, Week 52
| Intervention | units on a scale (Mean) |
|---|
| Fingolimod | 2.11 |
Change From Baseline in Symbol Digit Modalities Test (SDMT) at Week 24
The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution. (NCT02342704)
Timeframe: Baseline, Week 24
| Intervention | units on a scale (Mean) |
|---|
| Natalizumab | 3.79 |
| Fingolimod | 3.24 |
Cumulative Number of New or Enlarging T2 Lesions
(NCT02342704)
Timeframe: Baseline, Week 24
| Intervention | lesions (Mean) |
|---|
| Natalizumab | 1.33 |
| Fingolimod | 1.94 |
Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 24
As assessed by magnetic resonance imaging (MRI). (NCT02342704)
Timeframe: Baseline, Week 24
| Intervention | percentage change (Mean) |
|---|
| T1 Lesion Volume Change | T2 Lesion Volume Change |
|---|
| Fingolimod | 1.81 | 3.32 |
,| Natalizumab | 0.5 | 0.08 |
Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 52
As assessed by MRI. (NCT02342704)
Timeframe: Baseline, Week 52
| Intervention | percentage change (Mean) |
|---|
| T1 Lesion Volume Change | T2 Lesion Volume Change |
|---|
| Fingolimod | -15.31 | 5.6 |
Cumulative Number of New T1-Gd+ Lesions
(NCT02342704)
Timeframe: Baseline, Week 4, Week 12, Week 24
| Intervention | lesions (Mean) |
|---|
| From Baseline to Week 4 | From Baseline to Week 12 | From Baseline to Week 24 |
|---|
| Fingolimod | 1.69 | 2.27 | 2.6 |
,| Natalizumab | 0.62 | 0.68 | 0.72 |
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 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 |
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 |
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 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 |
Estimated Annualized Aggregate Relapse Rate (ARR)
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 the mean of the annualized ARRs for all patients in the group calculated as the total number of confirmed relapses divided by the total number of days on study, multiplied by 365.25. (NCT00289978)
Timeframe: Baseline to end of study (Month 24)
| Intervention | Relapses per year (Number) |
|---|
| Fingolimod 1.25 mg | 0.16 |
| Fingolimod 0.5 mg | 0.18 |
| Placebo | 0.40 |
Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline
The number of new or newly enlarged T2 lesions at Month 24 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. (NCT00289978)
Timeframe: Baseline to end of study (Month 24)
| Intervention | T2 lesions (Mean) |
|---|
| Fingolimod 1.25 mg | 2.5 |
| Fingolimod 0.5 mg | 2.5 |
| Placebo | 9.8 |
Percentage of Patients Free of Disability Progression at Month 24 Assessed With the 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) is calculated. Disability progression was determined by the following: 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. A 3-month confirmed disability progression required onset EDSS, 3-month confirming EDSS, and all EDSS in between to meet the disability progression criteria. Percent of free of disability progression was calculated using the Kaplan Meier method. (NCT00289978)
Timeframe: Baseline to end of study (Month 24)
| Intervention | Percentage of participants (Number) |
|---|
| Fingolimod 1.25 mg | 83.4 |
| Fingolimod 0.5 mg | 82.3 |
| Placebo | 75.9 |
Percentage of Patients Relapse-free at the End of the Study
Patients who did not experience any relapses confirmed by a neurologist during the study were regarded as relapse-free patients. (NCT00670449)
Timeframe: Baseline to the end of the study (up to 4 years)
| Intervention | Percentage of patients (Number) |
|---|
| Fingolimod 0.5 mg | 45.2 |
| Fingolimod 1.25 mg | 62.1 |
| Placebo-fingolimod | 48.3 |
Aggregate Annualized Relapse Rate (ARR) Based on Confirmed Relapses
The ARR was defined as the total number of relapses for all patients in the treatment arm / total number of days in the study for all patients in the treatment arm for the specific period of time × 365.25. General definition of relapse: Appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from the onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (< 37.5°C) or infection. A relapse was to be confirmed by a neurologist trained on the Expanded Disability Status Scale (EDSS). A relapse must be accompanied by an increase of at least half a step (0.5) on the EDSS or an increase of 1 point on 2 different Functional Systems (FS) of the EDSS or 2 points on 1 of the FS (excluding Bowel/Bladder or Cerebral FS). (NCT00670449)
Timeframe: Months 0-6, 6-12, 12-24, 24-36, 36-48, and 48 to the end of the study (up to 4 years)
| Intervention | Relapses per year (Number) |
|---|
| Month 0 to 6 (N=57, 54, 57) | Month 6 to 12 (N=47, 46, 50) | Month 12 to 24 (N=44, 43, 39) | Month 24 to 36 (N=41, 40, 34) | Month 36 to 48 (N=28, 23, 23) | Month 48 to end of study (N=8, 6, 3) |
|---|
| Fingolimod 0.5 mg | 0.539 | 0.227 | 0.166 | 0.191 | 0.164 | 0.000 |
,| Fingolimod 1.25 mg | 0.404 | 0.284 | 0.223 | 0.058 | 0.075 | 0.000 |
,| Placebo-fingolimod | 1.131 | 0.232 | 0.222 | 0.162 | 0.309 | 0.000 |
Change From Core Study Baseline in the Expanded Disability Status Scale (EDSS) Score
Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months. (NCT00670449)
Timeframe: Baseline to Months 12, 24, 36, 48, and end of study (up to 4 years)
| Intervention | Units on a scale (Mean) |
|---|
| Month 12 (N=45, 43, 40) | Month 24 (N=42, 40, 35) | Month 36 (N=25, 21, 23) | Month 48 (N=3, 4, 1) | End of study (N=37, 36, 32) |
|---|
| Fingolimod 0.5 mg | -0.02 | -0.12 | 0.16 | 1.17 | 0.00 |
,| Fingolimod 1.25 mg | -0.02 | -0.06 | -0.07 | -0.63 | -0.17 |
,| Placebo-fingolimod | -0.23 | -0.21 | -0.37 | 0.00 | -0.31 |
Percentage of Patients Free From 3-month and 6-month Confirmed Disability Progression at Their Last Expanded Disability Status Scale (EDSS) Assessment
Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months. (NCT00670449)
Timeframe: Baseline to the end of the study (up to 4 years)
| Intervention | Percentage of patients (Number) |
|---|
| Free from 3-month confirmed disability progression | Free from 6-month confirmed disability progression |
|---|
| Fingolimod 0.5 mg | 74.3 | 87.1 |
,| Fingolimod 1.25 mg | 82.4 | 90.7 |
,| Placebo-fingolimod | 90.6 | 92.3 |
Percentage of Patients Free of Gd-enhanced T1 Weighted Magnetic Resonance Imaging (MRI) Lesions
To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of Gd-enhanced T1 weighted MRI lesions were counted and recorded. Lesions expanding through several slices were counted as only 1 lesion. (NCT00670449)
Timeframe: Months 6, 9, 12, 18, 24, 36, and 48
| Intervention | Percentage of patients (Number) |
|---|
| Month 6 (N=44, 48, 50) | Month 9 (N=44, 39, 41) | Month 12 (N=44, 42, 36) | Month 18 (N=42, 40, 37) | Month 24 (N=38, 39, 33) | Month 36 (N=25, 21, 22) | Month 48 (N=3, 4, 1) |
|---|
| Fingolimod 0.5 mg | 88.6 | 90.9 | 97.7 | 92.9 | 94.7 | 92.0 | 100.0 |
,| Fingolimod 1.25 mg | 97.9 | 94.9 | 97.6 | 92.5 | 94.9 | 85.7 | 75.0 |
,| Placebo-fingolimod | 58.0 | 92.7 | 88.9 | 94.6 | 90.9 | 90.9 | 100.0 |
Percentage of Patients Free of New or Newly Enlarged T2 Weighted MRI Lesions
To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of new or newly enlarged T2 weighted MRI lesions were counted and recorded. New lesions were identified by comparing each lesion with previous scans. Lesions expanding through several slices were counted as only 1 lesion. (NCT00670449)
Timeframe: Months 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36,36-48, and 48 to the end of the study (up to 4 years)
| Intervention | Percentage of patients (Number) |
|---|
| Month 0 to 3 (N=49, 50, 51) | Month 3 to 6 (N=43, 47, 48) | Month 6 to 9 (N=44, 39, 40) | Month 9 to 12 (N=44, 42, 35) | Month 12 to 18 (N=43, 40, 37) | Month 18 to 24 (N=39, 39, 33) | Month 24 to 36 (N=25, 21, 22) | Month 36 to 48 (N=3, 4, 1) | Month 48 to end of study (N=3, 3, 1) |
|---|
| Fingolimod 0.5 mg | 69.4 | 86.0 | 88.6 | 93.2 | 88.4 | 94.9 | 92.0 | 100.0 | 100.0 |
,| Fingolimod 1.25 mg | 60.0 | 91.5 | 92.3 | 95.2 | 90.0 | 92.3 | 90.5 | 100.0 | 100.0 |
,| Placebo-fingolimod | 45.1 | 43.8 | 70.0 | 85.7 | 91.9 | 87.9 | 90.9 | 100.0 | 100.0 |
Annualized Aggregate Relapse Rate (ARR) During Months 0 to End of Study(Core [CFTY720D2301/NCT00289978] and Extension Study)
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 the mean of the annualized ARRs for all patients in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. (NCT00662649)
Timeframe: Months 0 to end of study (maximum up to 60 months)
| Intervention | Relapses per year (Number) |
|---|
| Fingolimod 1.25 mg | 0.164 |
| Fingolimod 0.5 mg | 0.185 |
| Placebo-fingolimod | 0.357 |
Change (Expressed as Ratio) in the Annualized Aggregate Relapse Rate (ARR) From Months 0-24 (Core Study) to Months 24-48 (Extension Study)
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 the mean of the annualized ARRs for all patients in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. (NCT00662649)
Timeframe: Months 0-24 (core study) and Months 24-48 (extension study)
| Intervention | Ratio of relapses per year (Number) |
|---|
| Fingolimod 1.25 mg | 1.164 |
| Fingolimod 0.5 mg | 0.850 |
| Placebo-fingolimod 1.25 mg | 0.547 |
| Placebo-fingolimod 0.5 mg | 0.446 |
Percent Change in Brain Volume From Month 0 End of Study (Core and Extension Study)
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. (NCT00662649)
Timeframe: Months 0 to end of study (maximum up to 60 months)
| Intervention | Percent change (Mean) |
|---|
| Fingolimod 1.25 mg | -1.639 |
| Fingolimod 0.5 mg | -1.674 |
| Placebo-fingolimod | -2.241 |
Time to First 3-month Confirmed Disability Progression up to End of Study Based on Expanded Disability Status Scale (EDSS): Kaplan-Meier Estimate of Percentage of Patients Free of Disability Progression
Kurtzke's Expanded Disability Status Scale (EDSS) is a scale for assessing neurologic impairment in multiple sclerosis (MS) includes a series of scores in each of eight functional systems such as Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, Cerebral, and Other. The EDSS steps range from 0 (normal) to 10 (death due to MS). The Kaplan-Meier estimates of the percentage of participants free of disability progression at end of study and their 95% CIs were provided for each treatment group. (NCT00662649)
Timeframe: Core baseline to end of study (maximum up to 60 months)
| Intervention | Percentage of patients (Number) |
|---|
| Fingolimod 1.25 mg | 74.15 |
| Fingolimod 0.5 mg | 73.90 |
| Placebo-fingolimod | 66.28 |
Time to First Confirmed Relapse up to End of Study: Kaplan-Meier Estimate of Percentage of Patients Relapse-free
A relapse was confirmed when it was accompanied by an increase of at least half a step (0.5) on the Expanded Disability Status Scale (EDSS) or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Kaplan-Meier estimates of the percentage of relapse-free patients at end of study and and 95% confidence intervals (CIs) were presented for the treatment groups. (NCT00662649)
Timeframe: Core baseline to end of study (maximum up to 60 months)
| Intervention | Percentage of patients (Number) |
|---|
| Fingolimod 1.25 mg | 59.85 |
| Fingolimod 0.5 mg | 59.29 |
| Placebo-fingolimod | 37.18 |
Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study)
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 the mean of the annualized ARRs for all patients in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. (NCT00662649)
Timeframe: Months 0-24 (core study) and Months 24-48 (extension study)
| Intervention | Relapses per year (Number) |
|---|
| Months 0-24 | Months 24-48 |
|---|
| Fingolimod 0.5 mg | 0.111 | 0.095 |
,| Fingolimod 1.25 mg | 0.064 | 0.074 |
,| Placebo-fingolimod 0.5 mg | 0.292 | 0.130 |
,| Placebo-fingolimod 1.25 mg | 0.301 | 0.164 |
Change in Mean Number of New or Newly Enlarged T2 Magnetic Resonance Imaging (MRI) Lesions During Months 0-24 (Core Study) and Months 24-48 (Extension Study)
The number of new or newly enlarged T2 lesions was assessed with T2-weighted 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. (NCT00662649)
Timeframe: Months 0-24 (core study) and Months 24-48 (extension study)
| Intervention | Lesions (Mean) |
|---|
| Months 0-24 | Months 24-48 | Change from Months 0-24 to Months 24-48 |
|---|
| Fingolimod 0.5 mg | 2.66 | 2.58 | -0.09 |
,| Fingolimod 1.25 mg | 2.14 | 1.71 | -0.43 |
,| Placebo-fingolimod 0.5 mg | 8.12 | 1.43 | -6.68 |
,| Placebo-fingolimod 1.25 mg | 12.83 | 2.34 | -10.48 |
Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study)
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. (NCT00662649)
Timeframe: Months 0-24 (core study) and Months 24-48 (extension study)
| Intervention | Percent change (Mean) |
|---|
| Month 0 to Month 24, n=75, 109, 41, 49 | Month 24 to Month 48, n=75, 109, 41, 49 |
|---|
| Fingolimod 0.5 mg | -0.983 | -0.780 |
,| Fingolimod 1.25 mg | -1.011 | -0.871 |
,| Placebo-fingolimod 0.5 mg | -1.419 | -0.903 |
,| Placebo-fingolimod 1.25 mg | -1.511 | -1.103 |
Percentage of Patients Free of New or Newly Enlarged T2 Magnetic Resonance Imaging (MRI) Lesions During Months 0-24 (Core Study) and Months 24-48 (Extension Study)
The number of new or newly enlarged T2 lesions was assessed with T2-weighted 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. (NCT00662649)
Timeframe: Months 0-24 (core study) and Months 24-48 (extension study)
| Intervention | Percentage of patients (Number) |
|---|
| Months 0-24 | Months 24-48 |
|---|
| Fingolimod 0.5 mg | 50.3 | 69.3 |
,| Fingolimod 1.25 mg | 53.2 | 57.1 |
,| Placebo-fingolimod 0.5 mg | 23.2 | 55.1 |
,| Placebo-fingolimod 1.25 mg | 18.5 | 52.3 |
Annualized Relapse Rate (ARR) at 6 Months
Annualized relapse rate (ARR) of the treatment group is calculated by taking the total number of confirmed relapses for all the patients in the treatment group divided by the total number of days on study for all patients in the group and multiplied by 365.25 to obtain the annual rate. (NCT00537082)
Timeframe: 6 Months
| Intervention | Relapses per year (Number) |
|---|
| FTY720 1.25 mg | 0.407 |
| FTY720 0.5 mg | 0.512 |
| Placebo | 1.131 |
Number of Patients Free of Gadolinium-enhanced T1-Weighted Magnetic Resonance Imaging (MRI) Lesions at Both Month 3 and Month 6
Brain Magnetic Resonance Imaging (MRI) was performed at Month 3 and Month 6. Gadolinium-enhancing lesions (active lesions) represent acute inflammatory activity only and dissipate within 2-8 weeks of appearance. MRI scans were analyzed by blinded readers at the central MRI Evaluation Center to ensure consistency. Any Gd-enhanced T1 weighted MRI data obtained less than 14 days after the steroid used to treat MS relapses is invalid and excluded. (NCT00537082)
Timeframe: Month 3 and Month 6
| Intervention | Participants (Number) |
|---|
| FTY720 1.25 mg | 43 |
| FTY720 0.5 mg | 35 |
| Placebo | 21 |
Number of Patients Free of MS Relapse up to Month 6 (Confirmed Relapse Only)
A relapse must have been confirmed by a neurologist and was confirmed when it was accompanied by an increase of at least half a step (0.5) on the Expanded Disability Status Scale (EDSS) or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). (NCT00537082)
Timeframe: up to Month 6
| Intervention | Participants (Number) |
|---|
| FTY720 1.25 mg | 45 |
| FTY720 0.5 mg | 45 |
| Placebo | 37 |
Number of Patients Free of New or Newly Enlarged T2 Lesions
The number of T2 lesions were obtained from MRI scans at Screening visit. The numbers of new/newly enlarging T2 lesions were obtained from MRI scans at Month 3 or more. New lesions were identified by comparing each lesion already seen in previous examinations. Lesions expanding throughout several slices were counted as only one lesion. (NCT00537082)
Timeframe: up to Month 3 and up to Month 6
| Intervention | Participants (Number) |
|---|
| Month 3 (n = 50, 49, 51) | Month 6 (n = 48, 48, 50) |
|---|
| FTY720 0.5 mg | 34 | 31 |
,| FTY720 1.25 mg | 30 | 28 |
,| Placebo | 23 | 18 |
Aggregate Annualized Relapse Rate (ARR) Estimate up to End of Study
"ARR is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all patients in the group divided by the sum of the number of days on study of all patients in the group and multiplied by 365.25.~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 demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or known infection. A relapse must be confirmed by the Independent Evaluating Physician (examining neurologist).~ARR estimates were calculated from a negative binomial regression model adjusted for treatment, pooled center, number of relapses in the previous 2 years prior to enrollment, and Baseline expanded disability status scale (EDSS)." (NCT00355134)
Timeframe: From Baseline until end of study (up to approximately 54 months).
| Intervention | relapses per year (Number) |
|---|
| Fingolimod 1.25 mg | 0.180 |
| Fingolimod 0.5 mg | 0.192 |
| Placebo | 0.363 |
Aggregate Annualized Relapse Rate (ARR) Estimate up to Month 24
"ARR is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all patients in the group divided by the sum of the number of days on study of all patients in the group and multiplied by 365.25.~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 demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or known infection. A relapse must be confirmed by the Independent Evaluating Physician (examining neurologist).~ARR estimates were calculated from a negative binomial regression model adjusted for treatment, pooled center, number of relapses in the previous 2 years prior to enrollment, and Baseline expanded disability status scale (EDSS)." (NCT00355134)
Timeframe: 24 months
| Intervention | relapses per year (Number) |
|---|
| Fingolimod 1.25 mg | 0.203 |
| Fingolimod 0.5 mg | 0.208 |
| Placebo | 0.403 |
Percentage of Participants Relapse-free up to End of Study
Estimates of the percentage of participants relapse-free at end of study were generated from Kaplan-Meier curves of the time to first relapse. 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 demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or infection. A relapse was confirmed by an Independent Evaluating Physician. (NCT00355134)
Timeframe: From Baseline until the end of study (up to approximately 54 months)
| Intervention | percentage of participants (Number) |
|---|
| Fingolimod 1.25 mg | 63.88 |
| Fingolimod 0.5 mg | 66.57 |
| Placebo | 49.12 |
Percentage of Participants Relapse-free up to Month 24
Estimates of the percentage of participants relapse-free at 24 months were generated from Kaplan-Meier curves of the time to first relapse. 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 demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or infection. A relapse was confirmed by an Independent Evaluating Physician. (NCT00355134)
Timeframe: 24 months
| Intervention | percentage of participants (Number) |
|---|
| Fingolimod 1.25 mg | 73.2 |
| Fingolimod 0.5 mg | 71.5 |
| Placebo | 52.7 |
Change From Baseline in Lesion Volume at Month 24 (Core Phase)
Change from Baseline in lesion volume was measured by MRI for T2 lesions and for T1 hypointense lesions. (NCT00355134)
Timeframe: Baseline and Month 24
| Intervention | mm^3 (Mean) |
|---|
| T2 lesions [N=248, 266, 251] | T1 hypointense lesions [N=247, 266, 248] |
|---|
| Fingolimod 0.5 mg | -223.27 | -111.28 |
,| Fingolimod 1.25 mg | -436.92 | -99.13 |
,| Placebo | 541.83 | -37.68 |
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z-score
The Multiple Sclerosis Functional Composite (MSFC) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation (Timed 25-Foot Walk), arm function (9-Hole Peg Test), and cognitive function (Paced Auditory Serial Addition Test). The overall MSFC z-score as an average of the three standardized scores derived using baseline data pooled over each treatment arm as reference population. Higher scores reflect better neurological function and a positive change from Baseline indicates improvement. (NCT00355134)
Timeframe: Baseline, Month 24 and end of study (up to approximately 54 months)
| Intervention | units on a scale (Mean) |
|---|
| Month 24 [N=250; 271; 258] | End of Study [N=174; 187; 184] |
|---|
| Fingolimod 0.5 mg | 0.00 | -0.091 |
,| Fingolimod 1.25 mg | -0.08 | 0.011 |
,| Placebo | -0.07 | 0.019 |
Number of Gadolinium-enhanced T1 Lesions
Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of gadolinium-enhanced T1 lesions. (NCT00355134)
Timeframe: Month 24 and end of study (up to approximately 54 months)
| Intervention | lesions (Mean) |
|---|
| Core Phase (Month 24) [N=251; 269; 256] | End of Extension study [N=184; 194; 184] |
|---|
| Fingolimod 0.5 mg | 0.37 | 0.09 |
,| Fingolimod 1.25 mg | 0.24 | 0.46 |
,| Placebo | 1.22 | 0.45 |
Number of New or Newly Enlarged T2 Lesions
Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of new or newly enlarged T2 lesions, by year. (NCT00355134)
Timeframe: From Baseline until Month 48
| Intervention | lesions (Mean) |
|---|
| Core Phase (Month 0 to 24) [N=245; 264; 251] | Month 24 to 36 [N=103; 111; 102] | Month 36 to 48 [N=24; 15; 15] |
|---|
| Fingolimod 0.5 mg | 2.3 | 0.45 | 0.07 |
,| Fingolimod 1.25 mg | 1.6 | 0.63 | 0.13 |
,| Placebo | 8.9 | 0.63 | 2.53 |
Percent Change From Baseline in Brain Volume
Brain volume was measured using magnetic resonance imaging (MRI). Change from Baseline in brain volume is expressed as a percentage of the Baseline brain volume. (NCT00355134)
Timeframe: Baseline, Month 24 and end of study (up to approximately 54 months)
| Intervention | percent change (Mean) |
|---|
| Month 24 [N=247; 266; 249] | End of study [N=178; 187; 182] |
|---|
| Fingolimod 0.5 mg | -0.858 | -1.266 |
,| Fingolimod 1.25 mg | -0.595 | -1.130 |
,| Placebo | -1.279 | -1.694 |
Percentage of Participants Free of 3-month Confirmed Disability Progression at Month 24 and End of Study
Disability progression was defined using the following criteria: One point increase from baseline in patients with Baseline Expanded Disability Status Scale (EDSS) score from 0 to 5.0; or half a point increase from Baseline in patients with Baseline EDSS score of 5.5 or above. A 3-month confirmed disability progression was defined as a 3-month sustained increase from Baseline in EDSS score. The EDSS quantifies disability in multiple sclerosis in 8 functional systems; the score ranges from 0 (normal) to 10 (death due to MS). Progression curves were generated by the Kaplan-Meier method. (NCT00355134)
Timeframe: 24 months and end of study (up to approximately 54 months)
| Intervention | percentage of participants (Number) |
|---|
| At month 24 | At end of study |
|---|
| Fingolimod 0.5 mg | 74.7 | 58.89 |
,| Fingolimod 1.25 mg | 78.3 | 66.64 |
,| Placebo | 71.0 | 63.51 |
Percentage of Participants Free of 6-month Confirmed Disability Progression at Month 24 and End of Study
Disability progression was defined using the following criteria: One point increase from baseline in patients with Baseline Expanded Disability Status Scale (EDSS) score from 0 to 5.0; or half a point increase from Baseline in patients with Baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined as a 6-month sustained increase from Baseline in EDSS score. The EDSS quantifies disability in multiple sclerosis in 8 functional systems; the score ranges from 0 (normal) to 10 (death due to MS). Progression curves were generated by the Kaplan-Meier method. (NCT00355134)
Timeframe: 24 months and end of study (up to approximately 54 months)
| Intervention | percentage of participants (Number) |
|---|
| At Month 24 | At end of study |
|---|
| Fingolimod 0.5 mg | 86.2 | 74.89 |
,| Fingolimod 1.25 mg | 86.9 | 79.92 |
,| Placebo | 82.2 | 75.03 |
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at End of Study
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. The last observation was the last observation available for each patient which ranged from 1 to 2801 days (NCT00333138)
Timeframe: Last observation (Up to 80 months in average)
| Intervention | GD- enhanced T1 lesions (Mean) |
|---|
| Placebo | 0.8 |
| Fingolimod (FTY720) 1.25 mg/Day | 0.4 |
| Fingolimod (FTY720) 5.0 mg/Day | 0.5 |
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 12
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. (NCT00333138)
Timeframe: Month 12 (extension)
| Intervention | GD- enhanced T1 lesions (Mean) |
|---|
| Placebo | 0.4 |
| Fingolimod (FTY720) 1.25 mg/Day | 1.0 |
| Fingolimod (FTY720) 5.0 mg/Day | 0.2 |
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core)
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. (NCT00333138)
Timeframe: Month 6 (Core)
| Intervention | GD- enhanced T1 lesions (Mean) |
|---|
| Placebo | 2.3 |
| Fingolimod (FTY720) 1.25 mg/Day | 1.4 |
| Fingolimod (FTY720) 5.0 mg/Day | 0.4 |
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 60
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. (NCT00333138)
Timeframe: Month 60 (extension)
| Intervention | GD- enhanced T1 lesions (Mean) |
|---|
| Placebo | 0.2 |
| Fingolimod (FTY720) 1.25 mg/Day | 0.2 |
| Fingolimod (FTY720) 5.0 mg/Day | 0.1 |
Change From Baseline in Volume of Total T2-weighted 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). The last observation was the last observation available for each patient which ranged from 1 to 2801 days. (NCT00333138)
Timeframe: Baseline to month 6, 12, 60 and Last observation (up to 80 months in average)
| Intervention | mm^3 (Mean) |
|---|
| Month 6 (core) n=85, 89, 86 | Month 12 (extension) n=73, 77, 71 | Month 60 (extension) n=45, 49, 43 | Last observation (extension) n= 87, 89, 87 |
|---|
| Fingolimod (FTY720) 1.25 mg/Day | -115.81 | 1.66 | -204.09 | -92.24 |
,| Fingolimod (FTY720) 5.0 mg/Day | -607.97 | -513.35 | -1429.98 | -907.48 |
,| Placebo | 146.15 | 144.96 | -621.82 | -178.86 |
Mean Number of New T2-weighted Lesions
New T2 lesions at a specific visit were assessed relative to the previous visit scan. The total number of lesions (Month 1 to end of study) is calculated as the sum of the number of lesions at Months 1 to 6, Month 12, Month 60 and last observation. The last observation was the last observation available for each patient which ranged from 1 to 2801 days (NCT00333138)
Timeframe: (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average)
| Intervention | GD enhanced T2 lesions (Mean) |
|---|
| Month 6 (Core), n= 82,88, 84 | Month 12 (Extension) n=71, 79, 71 | Month 60 (Extension) n=45, 50, 43 | Last observation (Extension) n=92, 93, 91 |
|---|
| Fingolimod (FTY720) 1.25 mg/Day | 0.5 | 1.4 | 0.5 | 0.6 |
,| Fingolimod (FTY720) 5.0 mg/Day | 0.1 | 0.6 | 0.3 | 0.5 |
,| Placebo | 1.0 | 0.8 | 0.4 | 0.7 |
Mean Trough Blood Concentrations of FTY720
For each patient, the arithmetic mean of the two FTY720 trough blood levels from month 3 and 6 was calculated. This was taken as the patient's steady-state trough levels. Venous blood samples (3 mL) were collected before the dose in ethylenediaminetetraacetic acid (EDTA)-containing tubes at protocol-scheduled visits at months 3 and 6 in all patients. (NCT00333138)
Timeframe: Month 3 and 6
| Intervention | ng/mL (Mean) |
|---|
| Month 3 (core) | Month 6 (core) |
|---|
| FTY720 1.25 mg/Day | 7.64 | 7.38 |
,| FTY720 5.0 mg/Day | 30.5 | 28.9 |
Percentage of Participants Free of T1-weighted Lesions
A patient was defined as free of lesions if s/he had zero lesions. The last observation was the last observation available for each patient which ranged from 1 to 2801 days (NCT00333138)
Timeframe: Baseline, Months 6 (core), 12, 60 and Last Observation (up to 80 months in average)
| Intervention | percentage of participants (Number) |
|---|
| Baseline (Core) n=93, 92, 93 | Month 6 (Core) n= 83, 90, 87 | Month 12 (Extension) n= 72, 77, 71 | Month 60 (Extension) n= 45, 49, 44 | Last observation (Extension) n= 92, 93, 92 |
|---|
| Fingolimod (FTY720) 1.25 mg/Day | 52.2 | 76.7 | 83.1 | 91.8 | 83.9 |
,| Fingolimod (FTY720) 5.0 mg/Day | 48.4 | 78.2 | 88.7 | 93.2 | 83.7 |
,| Placebo | 49.5 | 47.0 | 79.2 | 91.1 | 81.5 |
Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit
A patient was defined as free of lesions if s/he had zero lesions. The sum of all new T2-weighted lesions at Month 1 to last observation was zero (the sum is missing if one of the assessments was missing). New T2 lesions at a specific visit were assessed relative to the previous visit scan. Exception: new T2 lesions at Month 24 were assessed relative to Month 12. The last observation was the last observation available for each patient which ranged from 1 to 2801 days (NCT00333138)
Timeframe: Month 6 and 12, 60, last observation (up to 80 months in average)
| Intervention | percentage of paticipants (Number) |
|---|
| Month 6 (Core), n= 80, 87, 83 | Month 12 (Extension) n=70, 77, 70 | Month 60 (Extension) n=45, 49, 43 | Last observation (Extension) n=92, 93,90 |
|---|
| Fingolimod (FTY720) 1.25 mg/Day | 77.0 | 67.5 | 87.8 | 76.3 |
,| Fingolimod (FTY720) 5.0 mg/Day | 80.7 | 72.9 | 83.7 | 78.9 |
,| Placebo | 47.5 | 57.1 | 88.9 | 72.8 |
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
The Expanded Disability Status Scale (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. The last observation was the last observation available for each patient which ranged from 1 to 2801 days (NCT00333138)
Timeframe: Month 6,12,60 and Last observation (up to 80 months in average)
| Intervention | percentage of participants (Number) |
|---|
| 0 days (n=93,94,94) | 200 days (n=57, 73, 70) | 400 days (n=48, 63, 60) | 600 days (n=41, 57, 52) | 800 days (n=38, 48, 48) | 1000 days (n=35, 42, 45) | 1200 days (n=30, 38 40) | 1400 days (n=29, 36, 35) | 1600 days (n=27, 34, 34) | 1800 days (n=25, 33, 33) | 2000 days (n=23, 31, 31) | 2200 days (n=22, 28, 30) | 2400 days (n=21, 26, 27) | 2600 days (n=9, 12, 12) | 2880 days (n=0, 0, 0) |
|---|
| Fingolimod (FTY720) 1.25 mg/Day | 1.00 | 0.86 | 0.78 | 0.76 | 0.75 | 0.70 | 0.66 | 0.63 | 0.61 | 0.61 | 0.59 | 0.55 | 0.55 | 0.55 | 0 |
,| Fingolimod (FTY720) 5.0 mg/Day | 1.00 | 0.86 | 0.79 | 0.78 | 0.75 | 0.75 | 0.70 | 0.70 | 0.68 | 0.68 | 0.66 | 0.66 | 0.66 | 0.66 | 0 |
,| Placebo | 1.00 | 0.69 | 0.62 | 0.58 | 0.55 | 0.53 | 0.51 | 0.51 | 0.51 | 0.51 | 0.51 | 0.49 | 0.46 | 0.44 | 0 |
Volume of T2-weighted Lesions
Volume of total T2-weighted lesions by visit were summarized. The last observation was the last observation available for each patient which ranged from 1 to 2801 days (NCT00333138)
Timeframe: (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average)
| Intervention | mm^3 (Mean) |
|---|
| Month 6 (Core) n=85, 91, 87 | Month 12 (Extension) n= 73, 79, 72 | Month 60 (Extension) n=45, 50, 44 | Last observation (Extension) n=87, 91, 88 |
|---|
| Fingolimod (FTY720) 1.25 mg/Day | 10084.6 | 10707.1 | 9498.7 | 10090.2 |
,| Fingolimod (FTY720) 5.0 mg/Day | 8331.1 | 8363.2 | 6626.9 | 8061.8 |
,| Placebo | 9016.0 | 8264.1 | 6698.3 | 8757.2 |
Immune Response 3 Weeks After Seasonal Influenza Vaccination
"Percentage of participants who responded to treatment with the seasonal influenza vaccine 3 weeks after vaccination. Response was defined as patients fulfilling one of the following criteria for at least one of the three strains contained in the seasonal influenza vaccine:~Seroconversion: The pre-vaccination antibody titer measurement was <1:10 and the post-vaccination measurement is ≥1:40.~Significant increase in antibody titer: The pre-vaccination antibody titer measurement was ≥1:10 and the increase in antibody titer from this to the post-vaccination measurement is ≥ 4-fold." (NCT01199861)
Timeframe: Week 6 (pre-vaccination) and 3 weeks after vaccination (Study week 9)
| Intervention | percentage of participants (Number) |
|---|
| Fingolimod | 53.3 |
| Placebo | 83.7 |
Immune Response 3 Weeks After Tetanus Toxoid Booster
"Percentage of participants with an immune response to a single dose of tetanus toxoid three weeks after vaccination. A patient was considered a responder to tetanus toxoid booster vaccination if one of the following criteria was met:~Seroconversion: The pre-vaccination antibody titer measurement was <0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml.~Significant increase: The pre-vaccination antibody titer measurement was ≥0.1 IU/ml and the increase in antibody titer from this to the post-vaccination measurement was ≥4- fold." (NCT01199861)
Timeframe: Week 6 (pre-vaccination) and 3 weeks after vaccination (Study Week 9)
| Intervention | percentage of participants (Number) |
|---|
| Fingolimod | 40.0 |
| Placebo | 60.5 |
Immune Response 6 Weeks After Seasonal Influenza Vaccination
"Percentage of participants who responded to treatment with the seasonal influenza vaccine 6 weeks after vaccination. Response was defined as patients fulfilling one of the following criteria for at least one of the three strains contained in the seasonal influenza vaccine:~Seroconversion: The pre-vaccination antibody titer measurement was <1:10 and the post-vaccination measurement is ≥1:40.~Significant increase in antibody titer: The pre-vaccination antibody titer measurement was ≥1:10 and the increase in antibody titer from this to the post-vaccination measurement is ≥ 4-fold." (NCT01199861)
Timeframe: Week 6 (pre-vaccination) and 6 weeks after vaccination (Study week 12).
| Intervention | percentage of participants (Number) |
|---|
| Fingolimod | 43.2 |
| Placebo | 74.4 |
Immune Response 6 Weeks After Tetanus Toxoid Booster
"Percentage of participants with an immune response to a single dose of tetanus toxoid six weeks after vaccination. A patient was considered a responder to tetanus toxoid booster vaccination if one of the following criteria was met:~Seroconversion: The pre-vaccination antibody titer measurement was <0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml.~Significant increase: The pre-vaccination antibody titer measurement was ≥0.1 IU/ml and the increase in antibody titer from this to the post-vaccination measurement was ≥4- fold." (NCT01199861)
Timeframe: Week 6 (pre-vaccination) and 6 weeks after vaccination (Study Week 12)
| Intervention | percentage of participants (Number) |
|---|
| Fingolimod | 37.5 |
| Placebo | 48.8 |
Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 3 Weeks After Vaccination
Change from Baseline was expressed by the ratio of post-vaccination to pre-vaccination antibody titer for each of the three strains included in the seasonal influenza vaccine. Inhibition of an immune response to each strain included in the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo three weeks after a single dose of seasonal influenza vaccine. (NCT01199861)
Timeframe: Pre-vaccination (Week 6) and 3 weeks after vaccination (Study Week 9).
| Intervention | ratio (Number) |
|---|
| A/California/7/09(H1N1) | A/Perth/16/2009(H3N2) | B/Brisbane/60/2008 |
|---|
| Fingolimod | 2.45 | 0.49 | 1.34 |
,| Placebo | 4.14 | 0.36 | 2.40 |
Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 6 Weeks After Vaccination
Change from Baseline was expressed by the ratio of post-vaccination to pre-vaccination antibody titer for each of the three strains included in the seasonal influenza vaccine. Inhibition of an immune response to each strain included in the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo six weeks after a single dose of seasonal influenza vaccine. (NCT01199861)
Timeframe: Pre-vaccination (Week 6) and 6 weeks after vaccination (Study Week 12).
| Intervention | ratio (Number) |
|---|
| A/California/7/09(H1N1) | A/Perth/16/2009(H3N2) | B/Brisbane/60/2008 |
|---|
| Fingolimod | 1.81 | 0.36 | 1.08 |
,| Placebo | 2.91 | 0.28 | 2.07 |
Number of Participants With Adverse Events (AEs)
"Relationship to study drug was determined by the investigator (suspected/not suspected).~A serious AE is defined as an event which fulfills one of the following criteria:~is fatal or life-threatening;~results in persistent or significant disability/incapacity;~constitutes a congenital anomaly/birth defect;~requires inpatient hospitalization or prolongation of existing hospitalization;~is medically significant, i.e., jeopardizes the patient or may require intervention to prevent one of the outcomes listed above." (NCT01199861)
Timeframe: From first dose of study drug until 45 days after the last dose of study drug (130 days).
| Intervention | participants (Number) |
|---|
| Any adverse event | AE related to study drug | Serious adverse event | Adverse events leading to discontinuation |
|---|
| Fingolimod | 82 | 42 | 1 | 1 |
,| Placebo | 34 | 11 | 2 | 0 |
Change From Baseline in Patient-reported Activities of Daily Living (ADL) Using the Multiple Sclerosis Activities Scale (PRIMUS-Activities) at Month 6
The PRIMUS activity measure is a 15-item assessment of patient-reported ADL. The PRIMUS-Activities total score was calculated by summing the 15 item scores after recoding the responses from 1 - 3 to 0 - 2. Totals scores range from 0 to 30 with higher scores indicating greater activity limitation. If no more than 20% of the items were missing, the total score was the product of the mean response of the non-missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change from baseline indicates improvement. (NCT01216072)
Timeframe: Baseline, Month 6
| Intervention | units on a scale (Mean) |
|---|
| Fingolimod | -0.6 |
| Multiple Sclerosis Disease Modifying Treatments (MS DMTs) | -0.2 |
Change From Baseline in the Global Satisfaction Subscale of the Treatment Satisfaction Questionnaire for Medication (TSQM) at Month 6
The TSQM was developed and validated as a general measure for treatment satisfaction. It contains 14 items assessing the following 4 domains: effectiveness (sum of scores for questions 1 - 3), side effects (sum of scores for questions 4 - 8), convenience (sum of scores for questions 9 - 11) and Global Satisfaction (sum of scores for questions 12 - 14). The primary analysis was on Global Satisfaction. Question 12 scored as 1(not at all confident) to 5 (extremely confident); question 13 scored as 1(not at all certain) to 5(extremely certain); and question 14 scored as 1(extremely dissatisfied) to 7(extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement. (NCT01216072)
Timeframe: Baseline, Month 6
| Intervention | units on a scale (Mean) |
|---|
| Fingolimod | 22.5 |
| Multiple Sclerosis Disease Modifying Treatments (MS DMTs) | 3.5 |
Change From Baseline in the Patient-reported Convenience Subscale Using the TSQM v1.4
The convenience subscale was scored as follows: questions 9 and 10 scored as 1(extremely difficult) to 7 (extremely easy), and question 11 scored as 1(extremely inconvenient) to 7 (extremely convenient). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement. (NCT01216072)
Timeframe: Baseline, Month 6
| Intervention | units on a scale (Mean) |
|---|
| Fingolimod | 41.8 |
| Multiple Sclerosis Disease Modifying Treatments (MS DMTs) | 1.5 |
Change From Baseline in the Patient-reported Effectiveness Subscale Using the TSQM v1.4
The effectiveness scale was scored as follows: 1(extremely dissatisfied) to 7(extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement. (NCT01216072)
Timeframe: Baseline, Month 6
| Intervention | units on a scale (Mean) |
|---|
| Fingolimod | 15.5 |
| Multiple Sclerosis Disease Modifying Treatments (MS DMTs) | 2.8 |
Change From Baseline in the Patient-reported Side Effects Subscale Using the TSQM v1.4
The Side Effects subscale was scored as follows: question 4 scored as 0(no) or 1(yes); question 5 scored as 1(extremely bothersome) to 5(not at all bothersome); and questions 6 - 8 scored as 1(a great deal) to 5(not at all). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement. (NCT01216072)
Timeframe: Baseline, Month 6
| Intervention | units on a scale (Mean) |
|---|
| Fingolimod | 22.9 |
| Multiple Sclerosis Disease Modifying Treatments (MS DMTs) | 3.5 |
Change From Baseline in Patient-reported Depression Using the Beck Depression Inventory (BDI-II)
The Beck Depression Inventory (BDI-II) is a 21-question multiple-choice self-report inventory. Each item is scored from 0 to 3. The questions in the BDI-II refer to how the patient has been feeling over the past two weeks specifically. The BDI-II total score was calculated by summing the 21 item scores. Final scores ranged from 0 to 63 where higher scores indicated more severe depression. If no more than 20% of the items were missing, the total score was the product of the mean response of the non-missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change indicates improvement. (NCT01216072)
Timeframe: Baseline, Month 3, Month 6
| Intervention | units on a scale (Mean) |
|---|
| Change from Baseline to Month 3 (n=748,236) | Change from Baseline to Month 6 (n=709,223) |
|---|
| Fingolimod | -3.2 | -3.4 |
,| Multiple Sclerosis Disease Modifying Treatments (MS DMTs) | -0.8 | -0.6 |
Change From Baseline in Patient-reported Fatigue Using the Fatigue Severity Scale (FSS)
The Fatigue Severity Scale (FSS) is a 9-item assessment scale measuring fatigue and its effects, using a scale from 1 to 7, with higher scores indicating greater fatigue, or greater negative effects of fatigue on daily living. The FSS 9 item total score was calculated by summing the first 9 item scores and dividing by the number of non-missing items. If no more than 20% of the items were missing, the total score was the product of the mean response of the non missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change from baseline indicates improvement. (NCT01216072)
Timeframe: Baseline, Month 3, Month 6
| Intervention | units on a scale (Mean) |
|---|
| Change from Baseline to Month 3 (n=710,232) | Change from Baseline to Month 6 (n=687,218) |
|---|
| Fingolimod | -0.3 | -0.4 |
,| Multiple Sclerosis Disease Modifying Treatments (MS DMTs) | 0.0 | 0.0 |
Change From Baseline in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Standard (SF-36 v2)
The SF-36v2 is a validated health-related quality of life instrument used in numerous disease states, including MS. It is a self-administered survey that measures 8 domains of health including: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems and general mental health. Additionally, two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). If half or more questions within a domain were answered, then a score was calculated for that domain. Otherwise, the patient score for that domain was set to missing. If the patient was missing any 1 of the 8 scale scores, then the physical and mental component scores were set to missing. An algorithm was used to create a score from 0 to 100 for each domain score and component score. A positive change from baseline indicates improvement. (NCT01216072)
Timeframe: Baseline, Month 6
| Intervention | units on a scale (Mean) |
|---|
| Physical Function (n=745,226) | Role Limitations d/t Physical Health (n=742,226) | Bodily Pain (n=742,226) | General Health Perceptions (n=737,224) | Vitality (n=745,227) | Social Functioning (n=747,227) | Role Limitation d/t Emotional Problems (n=745,226) | General Mental Health (n=745,227) | Physical Component Summary Scale (n=724,222) | Mental Component Summary Scale (n=724,222) |
|---|
| Fingolimod | 1.5 | 2.8 | 2.0 | 0.8 | 2.8 | 2.6 | 1.6 | 2.2 | 1.7 | 2.3 |
,| Multiple Sclerosis Disease Modifying Treatments (MS DMTs) | 0.4 | 1.2 | -0.3 | -0.3 | 0.6 | 0.8 | -0.6 | 0.3 | 0.3 | 0.2 |
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death
In this analysis, patients with all (serious and non-serious) adverse events, serious adverse events and death were reported. (NCT01216072)
Timeframe: 9 months (6 month core + 3 month Extension)
| Intervention | Participants (Number) |
|---|
| Adverse Events (serious and non-serious) | Serious Adverse Events | Death |
|---|
| Extension Fingolimod Period | 123 | 7 | 0 |
,| Fingolimod | 617 | 31 | 0 |
,| Multiple Sclerosis Disease Modifying Treatments (MS DMTs) | 152 | 5 | 0 |
Physician-reported Clinical Global Impression of Improvement (CGI-I)
The CGI-I is a rating scale allowing a physician-reported global evaluation of the subject's improvement over time. The Investigator assessed the subject's clinical change relative to the symptoms at baseline on the CGI-I, a seven-point scale, with rating as follows: 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse, 7=Very much worse. The assessments were completed at Month 3 and Month 6. A lower score indicates improvement. (NCT01216072)
Timeframe: Month 3, Month 6
| Intervention | units on a scale (Mean) |
|---|
| Month 3 (n=758,242) | Month 6 (n=727,228) |
|---|
| Fingolimod | 3.4 | 3.2 |
,| Multiple Sclerosis Disease Modifying Treatments (MS DMTs) | 3.9 | 3.9 |
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 |
Part I: Aggregate Annualized Relapse Rates (ARR) From First Dose of Fingolimod
Annualized relapse rate (ARR) is defined as the number of all relapses (including both confirmed and unconfirmed relapses) experienced during a specific period of time adjusted to a one-year period. ARR is calculated as follows: (total number of all relapses) / (total number of days in the study for all patients for that specific period of time) x 365.25. Month 0 is the first dose of fingolimod study drug among all studies in which patient participated. Only descriptive analysis performed. (NCT01201356)
Timeframe: Month 0 (Core Baseline) to End of Follow-up Visit (an average of 162 months)
| Intervention | Annual number of relapses per patient (Number) |
|---|
| Month 0 to Month 6 | Month 0 to Month 12 | Month 0 to Month 24 | Month 0 to Month 36 | Month 0 to Month 48 | Month 0 to Month 60 | Month 0 to Month 72 | Month 0 to Month 84 | Month 0 to Month 96 | Month 0 to Month 108 | Month 0 to Month 120 | Month 0 to Month 132 | Month 0 to Month 144 | Month 0 to Month 156 | Month 0 to end of Study | Month 0 to end of Follow-up |
|---|
| Fingolimod 0.5 mg/Day | 0.325 | 0.273 | 0.237 | 0.217 | 0.208 | 0.197 | 0.190 | 0.182 | 0.177 | 0.172 | 0.170 | 0.170 | 0.169 | 0.169 | 0.166 | 0.169 |
Part I: Annualized Rate of Brain Atrophy (ARBA) Relative to First Dose of Fingolimod
"The annualized rate of brain volume change is an averaged annual percentage change in brain volume. ARBA was calculated as: ARBA = [(SIENA/100+1) ^ (365.25/#days)-1]*100 where SIENA=(Vk/V0-1)*100 and Vk is the brain volume at time k, V0 is the brain volume at time 0 and k is the total number of days in the study for all patients for that specific period of time) × 365.25. Only descriptive analysis performed." (NCT01201356)
Timeframe: Month 3 to Month 156
| Intervention | Ratio (Mean) |
|---|
| Month 3 | Month 6 | Month 12 | Month 24 | Month 36 | Month 48 | Month 60 | Month 72 | Month 84 | Month 96 | Month 108 | Month 120 | Month 132 | Month 144 | Month 156 |
|---|
| Fingolimod 0.5 mg/Day | -0.73 | -0.39 | -0.35 | -0.37 | -0.35 | -0.37 | -0.34 | -0.35 | -0.35 | -0.31 | -0.33 | -0.36 | -0.43 | -0.36 | -0.35 |
Part I: Annualized Rates of New or Newly Enlarging T2 Lesions (ARneT2) Compared With First Dose of Fingolimod
Annualized rate of new/newly enlarging T2 lesions (ARneT2) is defined as the number of new or newly enlarging T2 lesions experienced during a specific period of time adjusted to a one-year period. ARneT2 was calculated as follows: (total number of new/newly enlarging T2 lesions) / (total number of days in the study for all patients for that specific period of time) x 365.25.Month 0 is the first dose of fingolimod study drug among all studies in which patient participated. Only descriptive analysis performed. (NCT01201356)
Timeframe: Month 0 (Core Baseline) to End of Study (an average of Month 156)
| Intervention | Annual number of T2 lesions per patient (Number) |
|---|
| Month 0 to Month 3 | Month 0 to Month 6 | Month 0 to Month 12 | Month 0 to Month 24 | Month 0 to Month 36 | Month 0 to Month 48 | Month 0 to Month 60 | Month 0 to Month 72 | Month 0 to Month 84 | Month 0 to Month 96 | Month 0 to Month 108 | Month 0 to Month 120 | Month 0 to Month 132 | Month 0 to Month 144 | Month 0 to Month 156 | Month 0 to end of study |
|---|
| Fingolimod 0.5 mg/Day | 12.324 | 2.073 | 1.360 | 1.042 | 1.011 | 1.008 | 0.957 | 0.963 | 0.906 | 0.813 | 0.713 | 0.702 | 0.659 | 0.681 | 0.637 | 0.751 |
Part I: Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS)
The EDSS is a scale for assessing neurological impairment in MS (Kurtzke 1983) including (1) a series of scores in each of eight functional systems, and (2) the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Based on the assessment of each FS, the participant's overall score is determined between 0 to 10. A negative change from baseline indicates improvement. Only descriptive analysis performed. (NCT01201356)
Timeframe: Month 0 (Core Baseline) to End of Follow-up Visit (an average of 162 months)
| Intervention | EDDS Overall Score (Mean) |
|---|
| Baseline (BL) | Change from BL at Month 3 | Change from BL at Month 6 | Change from BL at Month 9 | Change from BL at Month 12 | Change from BL at Month 15 | Change from BL at Month 18 | Change from BL at Month 21 | Change from BL at Month 24 | Change from BL at Month 27 | Change from BL at Month 30 | Change from BL at Month 33 | Change from BL at Month 36 | Change from BL at Month 39 | Change from BL at Month 42 | Change from BL at Month 45 | Change from BL at Month 48 | Change from BL at Month 51 | Change from BL at Month 54 | Change from BL at Month 57 | Change from BL at Month 60 | Change from BL at Month 63 | Change from BL at Month 66 | Change from BL at Month 69 | Change from BL at Month 72 | Change from BL at Month 75 | Change from BL at Month 78 | Change from BL at Month 81 | Change from BL at Month 84 | Change from BL at Month 87 | Change from BL at Month 90 | Change from BL at Month 93 | Change from BL at Month 96 | Change from BL at Month 99 | Change from BL at Month 102 | Change from BL at Month 105 | Change from BL at Month 108 | Change from BL at Month 111 | Change from BL at Month 114 | Change from BL at Month 117 | Change from BL at Month 120 | Change from BL at Month 123 | Change from BL at Month 126 | Change from BL at Month 129 | Change from BL at Month 132 | Change from BL at Month 135 | Change from BL at Month 138 | Change from BL at Month 141 | Change from BL at Month 144 | Change from BL at Month 147 | Change from BL at Month 150 | Change from BL at Month 153 | Change from BL at Month 156 | Change from BL at Month 159 | Change from BL at Month 162 | Change from BL at End of study | Change from BL at Month 3 follow-up | Change from BL at Month 6 follow-up |
|---|
| Fingolimod 0.5 mg/Day | 2.39 | -0.06 | -0.07 | -0.09 | -0.07 | -0.08 | -0.05 | -0.08 | -0.01 | -0.03 | -0.00 | -0.02 | 0.01 | 0.02 | 0.04 | 0.06 | 0.06 | 0.06 | 0.04 | 0.09 | 0.17 | 0.08 | 0.15 | 0.14 | 0.22 | 0.13 | 0.28 | 0.18 | 0.25 | 0.24 | 0.29 | 0.18 | 0.31 | 0.18 | 0.30 | 0.21 | 0.28 | 0.24 | 0.30 | 0.35 | 0.40 | 0.60 | 0.38 | 0.40 | 0.40 | 0.51 | 0.42 | 0.54 | 0.60 | 0.67 | 0.44 | 0.23 | 0.26 | 1.17 | 0.75 | 0.14 | 0.29 | 0.56 |
Part I: Change From First Dose of Fingolimod in Total T1 Hypointense Lesions Volume
T1 hypointense lesion (black hole) volume was summarized by presenting descriptive statistics for change from first dose of fingolimod baseline values by visit. (NCT01201356)
Timeframe: Month 3 to End of Study (Study Completion Visit)
| Intervention | mm^3 (Mean) |
|---|
| T1 volume change at Month 3 | T1 volume change at Month 12 | T1 volume change at Month 24 | T1 volume change at Month 36 | T1 volume change at Month 48 | T1 volume change at Month 60 | T1 volume change at Month 72 | T1 volume change at Month 84 | T1 volume change at Month 96 | T1 volume change at Month 108 | T1 volume change at Month 120 | T1 volume change at Month 132 | T1 volume change at End of Study |
|---|
| Fingolimod 0.5 mg/Day | -519.8 | 49.1 | 64.1 | 151.08 | 524.8 | 853.6 | 975.7 | 930.1 | 753.4 | 628.7 | 817.3 | 726.7 | 800.6 |
Part I: Change From First Dose of Fingolimod in Total T2 Lesions Volume
Total volume of T2 lesions was summarized by presenting descriptive statistics for change from first dose of fingolimod baseline values by visit. (NCT01201356)
Timeframe: Month 3 to End of Study (Study Completion Visit)
| Intervention | mm^3 (Mean) |
|---|
| T2 volume change at Month 3 | T2 volume change at Month 6 | T2 volume change at Month 12 | T2 volume change at Month 24 | T2 volume change at Month 36 | T2 volume change at Month 48 | T2 volume change at Month 60 | T2 volume change at Month 72 | T2 volume change at Month 84 | T2 volume change at Month 96 | T2 volume change at Month 108 | T2 volume change at Month 120 | T2 volume change at Month 132 | T2 volume change at Month 144 | T2 volume change at Month 156 | T2 volume change at End of Study |
|---|
| Fingolimod 0.5 mg/Day | -749.5 | -207.0 | -55.0 | 16.2 | 235.8 | 875.1 | 1546.3 | 1719.2 | 1635.8 | 1303.9 | 1562.0 | 1393.1 | 905.9 | 702.7 | 274.0 | 1588.5 |
Part I: Number of Participants With Confirmed 6-month Disability Progression After First Dose of Fingolimod
Disability progression was defined based on an increase in the EDSS score by 1.5 point for patients with a first dose of fingolimod (FDF) baseline EDSS score of 0, 1 point for patients with FDF baseline EDSS of >=1 and <=5.5, and by 0.5 points for patients with an FDF baseline EDSS>5.5, confirmed after 6 months and all intermediate EDSS assessments. A 6-month confirmed disability progression was defined as a 6-month sustained increase from the reference (potential onset of progression) value in the EDSS scores. i.e., every EDSS score (scheduled or unscheduled) within a 6-month duration after the first progression should meet the progression criteria as specified above. The confirmation could only happen at a scheduled visit and in the absence of a relapse. Only descriptive analysis performed. (NCT01201356)
Timeframe: Month 12 to Month 156
| Intervention | Participants (Number) |
|---|
| Month 12 | Month 24 | Month 36 | Month 48 | Month 60 | Month 72 | Month 84 | Month 96 | Month 108 | Month 120 | Month 132 | Month 144 | Month 156 |
|---|
| Fingolimod 0.5 mg/Day | 212 | 336 | 434 | 519 | 590 | 659 | 714 | 753 | 767 | 772 | 775 | 776 | 777 |
Part I: Number of Participants With Relapses (Confirmed and Unconfirmed) From First Dose of Fingolimod
"A relapse is 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 demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5°C) or infection.~In Study Part One, a relapse must be confirmed by an Expanded Disability Status Scale (EDSS) certified Physician within 7 days of the onset of symptoms. A relapse is confirmed when it is accompanied by an increase of at least half a step (0.5) on the EDSS or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Month 0 is the first dose of fingolimod study drug among all studies in which patient participated. Only descriptive analysis performed." (NCT01201356)
Timeframe: Month 0 (Core Baseline) to End of Follow-up Visit (an average of 162 months)
| Intervention | Participants (Number) |
|---|
| Month 0 to Month 6 | Month 0 to Month 12 | Month 0 to Month 24 | Month 0 to Month 36 | Month 0 to Month 48 | Month 0 to Month 60 | Month 0 to Month 72 | Month 0 to Month 84 | Month 0 to Month 96 | Month 0 to Month 108 | Month 0 to Month 120 | Month 0 to Month 132 | Month 0 to Month 144 | Month 0 to Month 156 | Month 0 to end of Study | Month 0 to end of Follow-up |
|---|
| Fingolimod 0.5 mg/Day | 655 | 992 | 1461 | 1794 | 2127 | 2383 | 2616 | 2793 | 2944 | 3036 | 3063 | 3072 | 3075 | 3079 | 2970 | 3079 |
Part I: Percent Brain Volume Change (PBVC) Relative to First Dose of Fingolimod
Descriptive statistics on percent brain volume change from first dose of fingolimod baseline were presented by visit. A negative change from baseline indicates improvement. (NCT01201356)
Timeframe: Month 3 to Month 156
| Intervention | Percent change (Mean) |
|---|
| Percent volume change at Month 3 | Percent volume change at Month 6 | Percent volume change at Month 12 | Percent volume change at Month 24 | Percent volume change at Month 36 | Percent volume change at Month 48 | Percent volume change at Month 60 | Percent volume change at Month 72 | Percent volume change at Month 84 | Percent volume change at Month 96 | Percent volume change at Month 108 | Percent volume change at Month 120 | Percent volume change at Month 132 | Percent volume change at Month 144 | Percent volume change at Month 156 |
|---|
| Fingolimod 0.5 mg/Day | -0.19 | -0.20 | -0.36 | -0.74 | -1.03 | -1.44 | -1.65 | -2.02 | -2.38 | -2.41 | -2.91 | -3.42 | -4.61 | -4.21 | -4.33 |
Parts I and II: Number of Participants With Adverse Events, Serious Adverse Event, and Death
Analysis of absolute and relative frequencies for Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that Fingolimod 0.5 mg/day is safe in patients with relapsing forms of Multiple Sclerosis (MS) through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed. (NCT01201356)
Timeframe: Baseline (Part I) to Month 6 Follow-up (Part II), up to 8 years
| Intervention | Participants (Count of Participants) |
|---|
| Adverse Event (AEs) | Serious Adverse Events (SAEs) | Deaths |
|---|
| Fingolimod 0.5 mg/Day | 2125 | 515 | 16 |
Part I: Number of Participants With Categorized Change From First Dose of Fingolimod in Expanded Disability Status Scale (EDSS) Overall Score
"The EDSS is a scale for assessing neurological impairment in MS (Kurtzke 1983) including (1) a series of scores in each of eight functional systems, and (2) the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Based on the assessment of each FS, the participant's overall score is categorized as Improvement, Stable or Deterioration.~If baseline EDSS score is <=5, improvement is indicated by an EDSS score change of <= -1, stable is indicated by an EDSS score change of > -1 and <= 0.5, deterioration is indicated by an EDSS score change of > 0.5; if baseline EDSS score is > 5, improvement is indicated by an EDSS score change of <= -0.5, stable is indicated by an EDSS score change of > -0.5 and <= 0, deterioration is indicated by an EDSS score change of > 0. Only descriptive analysis performed." (NCT01201356)
Timeframe: Month 3 to Month 6 Follow-up
| Intervention | Participants (Count of Participants) |
|---|
| Month 372327500 | Month 672327500 | Month 972327500 | Month 1272327500 | Month 1572327500 | Month 1872327500 | Month 2172327500 | Month 2472327500 | Month 2772327500 | Month 3072327500 | Month 3372327500 | Month 3672327500 | Month 3972327500 | Month 4272327500 | Month 4572327500 | Month 4872327500 | Month 5172327500 | Month 5472327500 | Month 5772327500 | Month 6072327500 | Month 6372327500 | Month 6672327500 | Month 6972327500 | Month 7272327500 | Month 7572327500 | Month 7872327500 | Month 8172327500 | Month 8472327500 | Month 8772327500 | Month 9072327500 | Month 9372327500 | Month 9672327500 | Month 9972327500 | Month 10272327500 | Month 10572327500 | Month 10872327500 | Month 11172327500 | Month 11472327500 | Month 11772327500 | Month 12072327500 | Month 12372327500 | Month 12672327500 | Month 12972327500 | Month 13272327500 | Month 13572327500 | Month 13872327500 | Month 14172327500 | Month 14472327500 | Month 14772327500 | Month 15072327500 | Month 15372327500 | Month 15672327500 | Month 15972327500 | Month 16272327500 | End of study72327500 | Month 3 follow-up72327500 | Month 6 follow-up72327500 |
|---|
| Improvement | Stable | Deterioration |
|---|
| Fingolimod 0.5 mg/Day | 374 |
| Fingolimod 0.5 mg/Day | 3126 |
| Fingolimod 0.5 mg/Day | 269 |
| Fingolimod 0.5 mg/Day | 508 |
| Fingolimod 0.5 mg/Day | 2900 |
| Fingolimod 0.5 mg/Day | 340 |
| Fingolimod 0.5 mg/Day | 482 |
| Fingolimod 0.5 mg/Day | 2425 |
| Fingolimod 0.5 mg/Day | 304 |
| Fingolimod 0.5 mg/Day | 422 |
| Fingolimod 0.5 mg/Day | 1930 |
| Fingolimod 0.5 mg/Day | 322 |
| Fingolimod 0.5 mg/Day | 405 |
| Fingolimod 0.5 mg/Day | 1764 |
| Fingolimod 0.5 mg/Day | 285 |
| Fingolimod 0.5 mg/Day | 345 |
| Fingolimod 0.5 mg/Day | 1361 |
| Fingolimod 0.5 mg/Day | 271 |
| Fingolimod 0.5 mg/Day | 376 |
| Fingolimod 0.5 mg/Day | 1524 |
| Fingolimod 0.5 mg/Day | 320 |
| Fingolimod 0.5 mg/Day | 1299 |
| Fingolimod 0.5 mg/Day | 294 |
| Fingolimod 0.5 mg/Day | 313 |
| Fingolimod 0.5 mg/Day | 1271 |
| Fingolimod 0.5 mg/Day | 270 |
| Fingolimod 0.5 mg/Day | 305 |
| Fingolimod 0.5 mg/Day | 1204 |
| Fingolimod 0.5 mg/Day | 326 |
| Fingolimod 0.5 mg/Day | 1172 |
| Fingolimod 0.5 mg/Day | 292 |
| Fingolimod 0.5 mg/Day | 309 |
| Fingolimod 0.5 mg/Day | 1065 |
| Fingolimod 0.5 mg/Day | 288 |
| Fingolimod 0.5 mg/Day | 284 |
| Fingolimod 0.5 mg/Day | 1015 |
| Fingolimod 0.5 mg/Day | 276 |
| Fingolimod 0.5 mg/Day | 282 |
| Fingolimod 0.5 mg/Day | 948 |
| Fingolimod 0.5 mg/Day | 287 |
| Fingolimod 0.5 mg/Day | 875 |
| Fingolimod 0.5 mg/Day | 263 |
| Fingolimod 0.5 mg/Day | 250 |
| Fingolimod 0.5 mg/Day | 838 |
| Fingolimod 0.5 mg/Day | 264 |
| Fingolimod 0.5 mg/Day | 244 |
| Fingolimod 0.5 mg/Day | 784 |
| Fingolimod 0.5 mg/Day | 247 |
| Fingolimod 0.5 mg/Day | 256 |
| Fingolimod 0.5 mg/Day | 788 |
| Fingolimod 0.5 mg/Day | 251 |
| Fingolimod 0.5 mg/Day | 694 |
| Fingolimod 0.5 mg/Day | 245 |
| Fingolimod 0.5 mg/Day | 175 |
| Fingolimod 0.5 mg/Day | 577 |
| Fingolimod 0.5 mg/Day | 234 |
| Fingolimod 0.5 mg/Day | 182 |
| Fingolimod 0.5 mg/Day | 540 |
| Fingolimod 0.5 mg/Day | 191 |
| Fingolimod 0.5 mg/Day | 165 |
| Fingolimod 0.5 mg/Day | 499 |
| Fingolimod 0.5 mg/Day | 216 |
| Fingolimod 0.5 mg/Day | 503 |
| Fingolimod 0.5 mg/Day | 193 |
| Fingolimod 0.5 mg/Day | 440 |
| Fingolimod 0.5 mg/Day | 206 |
| Fingolimod 0.5 mg/Day | 156 |
| Fingolimod 0.5 mg/Day | 437 |
| Fingolimod 0.5 mg/Day | 201 |
| Fingolimod 0.5 mg/Day | 136 |
| Fingolimod 0.5 mg/Day | 398 |
| Fingolimod 0.5 mg/Day | 226 |
| Fingolimod 0.5 mg/Day | 150 |
| Fingolimod 0.5 mg/Day | 456 |
| Fingolimod 0.5 mg/Day | 217 |
| Fingolimod 0.5 mg/Day | 132 |
| Fingolimod 0.5 mg/Day | 407 |
| Fingolimod 0.5 mg/Day | 207 |
| Fingolimod 0.5 mg/Day | 147 |
| Fingolimod 0.5 mg/Day | 450 |
| Fingolimod 0.5 mg/Day | 227 |
| Fingolimod 0.5 mg/Day | 120 |
| Fingolimod 0.5 mg/Day | 413 |
| Fingolimod 0.5 mg/Day | 204 |
| Fingolimod 0.5 mg/Day | 143 |
| Fingolimod 0.5 mg/Day | 386 |
| Fingolimod 0.5 mg/Day | 187 |
| Fingolimod 0.5 mg/Day | 117 |
| Fingolimod 0.5 mg/Day | 375 |
| Fingolimod 0.5 mg/Day | 186 |
| Fingolimod 0.5 mg/Day | 110 |
| Fingolimod 0.5 mg/Day | 325 |
| Fingolimod 0.5 mg/Day | 159 |
| Fingolimod 0.5 mg/Day | 283 |
| Fingolimod 0.5 mg/Day | 154 |
| Fingolimod 0.5 mg/Day | 103 |
| Fingolimod 0.5 mg/Day | 261 |
| Fingolimod 0.5 mg/Day | 131 |
| Fingolimod 0.5 mg/Day | 87 |
| Fingolimod 0.5 mg/Day | 138 |
| Fingolimod 0.5 mg/Day | 74 |
| Fingolimod 0.5 mg/Day | 198 |
| Fingolimod 0.5 mg/Day | 101 |
| Fingolimod 0.5 mg/Day | 181 |
| Fingolimod 0.5 mg/Day | 79 |
| Fingolimod 0.5 mg/Day | 31 |
| Fingolimod 0.5 mg/Day | 94 |
| Fingolimod 0.5 mg/Day | 52 |
| Fingolimod 0.5 mg/Day | 88 |
| Fingolimod 0.5 mg/Day | 42 |
| Fingolimod 0.5 mg/Day | 14 |
| Fingolimod 0.5 mg/Day | 45 |
| Fingolimod 0.5 mg/Day | 26 |
| Fingolimod 0.5 mg/Day | 11 |
| Fingolimod 0.5 mg/Day | 36 |
| Fingolimod 0.5 mg/Day | 10 |
| Fingolimod 0.5 mg/Day | 39 |
| Fingolimod 0.5 mg/Day | 18 |
| Fingolimod 0.5 mg/Day | 12 |
| Fingolimod 0.5 mg/Day | 30 |
| Fingolimod 0.5 mg/Day | 19 |
| Fingolimod 0.5 mg/Day | 21 |
| Fingolimod 0.5 mg/Day | 7 |
| Fingolimod 0.5 mg/Day | 22 |
| Fingolimod 0.5 mg/Day | 15 |
| Fingolimod 0.5 mg/Day | 16 |
| Fingolimod 0.5 mg/Day | 8 |
| Fingolimod 0.5 mg/Day | 3 |
| Fingolimod 0.5 mg/Day | 9 |
| Fingolimod 0.5 mg/Day | 5 |
| Fingolimod 0.5 mg/Day | 2 |
| Fingolimod 0.5 mg/Day | 6 |
| Fingolimod 0.5 mg/Day | 0 |
| Fingolimod 0.5 mg/Day | 1 |
| Fingolimod 0.5 mg/Day | 610 |
| Fingolimod 0.5 mg/Day | 2419 |
| Fingolimod 0.5 mg/Day | 785 |
| Fingolimod 0.5 mg/Day | 203 |
| Fingolimod 0.5 mg/Day | 907 |
| Fingolimod 0.5 mg/Day | 381 |
| Fingolimod 0.5 mg/Day | 29 |
| Fingolimod 0.5 mg/Day | 111 |
Percentage of Participants With Disability Progression as Measured by Expanded Disability Status Scale (EDSS) (FAS)
"EDSS is a scale for assessing neurologic impairment in MS. It is a two-part system including~(1) a series of scores in each of eight functional systems, and (2) the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The definition of disability progression was based on increases in EDSS from baseline and depended on the EDSS baseline value: Disability progression was defined as a 1.5 increase in EDSS from baseline in subjects with a baseline EDSS score between 0.0 and 0.5, as a 1.0 increase in EDSS from baseline in subjects with a baseline EDSS score between 1.0 and 5.0 inclusive and 0.5 increase from baseline in subjects with EDSS score > 5.0." (NCT02720107)
Timeframe: Baseline up to approximately 48 months
| Intervention | percentage of participants (Number) |
|---|
| Fingolimod | 21.54 |
Change From Baseline in Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at Month 6 and Month 48 (FAS)
"EDSS is a scale for assessing neurologic impairment in MS. It is a two-part system including~(1) a series of scores in each of eight functional systems, and (2) the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The definition of disability progression was based on increases in EDSS from baseline and depended on the EDSS baseline value: Disability progression was defined as a 1.5 increase in EDSS from baseline in subjects with a baseline EDSS score between 0.0 and 0.5, as a 1.0 increase in EDSS from baseline in subjects with a baseline EDSS score between 1.0 and 5.0 inclusive and 0.5 increase from baseline in subjects with EDSS score > 5.0." (NCT02720107)
Timeframe: Baseline, month 6 up to approximately 48 months
| Intervention | scores on a scale (Mean) |
|---|
| Baseline | Month 6 | Month 48 | Change from baseline to month 6 | Change from month 6 to month 48 | Change from baseline to month 48 |
|---|
| Fingolimod | 2.7 | 2.6 | 2.7 | -0.1 | 0.2 | 0.0 |
Change in Immune Status of B Cells, Monocytes and Natural Killer Cells (NK) Cells (FAS)
Changes in immune status of B cells (CD19+, CD20+, CD69+), monocytes (CD14+) and NK cells (CD56+) were analyzed as a percentage of parent cell population (CD4+, CD8+ or total lymphocytes) by flow cytometry (NCT02720107)
Timeframe: Baseline up to approximately 48 months
| Intervention | percentage of parent population (Least Squares Mean) |
|---|
| B cells | Monocytes | Natural Killer cells |
|---|
| Fingolimod | -7.2 | 42.3 | 28.0 |
Change in T Cells Status (Decrease or Increase) at Month 48 (FAS)
Aim of trial was to was to show reduction of CD4+ and CD8+ naïve T cells (CCR7+CD45RA+), central memory T cells (CCR7+CD45RA-), central memory Th17 cells (CD4+ CCR4+ and CCR6+), and an elevation of 2 types of effector memory T cells TEM (CCR7- CD45RA-) and TEMRA (CCR7- CD45RA+) in peripheral venous blood. Changes from baseline to month 48 in biomarkers were analyzed for all patients in the FAS. (NCT02720107)
Timeframe: Baseline up to approximately 48 months
| Intervention | percentage of parent population (Least Squares Mean) |
|---|
| CD4+ Naïve T cells | CD4+Central memory T cells | CD4+ Effector memory T cells | CD8+ Naïve T cells | CD8+ Central memory T cells | CD8+ Effector memory T cells | TH17 central memory cells |
|---|
| Fingolimod | -23.7 | -1.2 | 22.2 | -37.2 | -1.6 | -12.9 | -0.6 |
Number of Particpants With Adverse Events as a Measure of Safety and Tolerability
Number of particpants with Adverse events as a measure of safety and tolerability (NCT01757691)
Timeframe: Weeks 0, 4, 8, 12, 18, 24, 36, 48, 60
| Intervention | Participants (Number) |
|---|
| Adverse Events (AE) | Death | Non -Fatal Seriuos Aderse Event (SAE) |
|---|
| Fingolimod 0.5mg/Daily | 1 | 0 | 0 |
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 |
Change in Patient-reported Health-related Quality-of-life Using the Short Form Health Survey v2 Acute (SF-36 v2 Acute)
The SF-36 is a health-related quality of life instrument used in numerous disease states, including MS (Brazier et al 1992). It is a self-administered survey that measures 8 domains of health including: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems and general mental health. Two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Each domain was scored by adding the individual items from the domain and transforming the resulting scores into a 0 to 100 scale with higher scores indicating better health status or functioning. (NCT01534182)
Timeframe: Baseline, 6 months
| Intervention | scores on scale (Mean) |
|---|
| Physical functioning (n=225,61) | Role limitations due to physical health (n=226,61) | Bodily pain (n=225,61) | General health (n=226,61) | Vitality (n=226,61) | Social functioning (n=226,61) | Role limit. due to emotional problems (n=224,61) | Mental health (n=226,61) | Physical component summary (n=222,61) | Mental component summary (n=222,61) |
|---|
| Fingolimod | 3.62 | 6.50 | 5.24 | 4.28 | 7.72 | 5.59 | 7.18 | 5.60 | 1.51 | 3.16 |
,| Standard Disease Modifying Therapy (DMT) | 1.39 | 4.30 | 0.93 | 4.43 | 1.95 | 1.64 | 5.33 | 2.79 | 0.68 | 1.68 |
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 |
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
"Peripheral blood chemokine cytokine levels measured by flow cytometry at baseline and between visits during fingolimod treatment.~Absolute counts of the cells were calculated according to the absolute lymphocyte counts and the percentages of cells. This allowed for a clear determination of cell counts and thus increased the reliability of the results." (NCT02373098)
Timeframe: Baseline, Month 3, Month 6
| Intervention | absolute cell count (Mean) |
|---|
| CD3CD4 (Lymphogate) | CD3CD8 (Lymphogate) | CD3CD4 (CD3 gate) | CD3CD8 (CD3 gate) | CD4+IFNg+ (in CD4+) | CD4+IL17+ (in CD4+) | CD8+IFNg+ (in CD8+) | CD8+IL17+ (in CD8+) | IFNg+ (in CD4+CD25+) | IL17+ (in CD4+CD25+) | CD4+IL10+ (in CD4+) | CD4+IL4+ (in CD4+) | CD4-CD8-IL4+ (in CD4-CD8-) | CD8+IL10+ (in CD8+) | IL10+ (in CD4+CD25+) | IL4+ (in CD4+CD25+) | CD4+TNFa+ (in CD4+) | CD4+IL9+ (in CD4+) | CD8+TNFa+ (in CD8+) | CD8+IL9+ (in CD8+) | TNFa+ (in CD4+CD25+) | IL9+ (in CD4+CD25+) |
|---|
| Healthy Controls | 41.19 | 23.23 | 57.38 | 35.11 | 7.42 | 1.23 | 16.45 | 1.71 | 7.1 | 2.35 | 1.64 | 1.44 | 1.31 | 0.52 | 2.57 | 1.88 | 46.86 | 0.22 | 35 | 0.14 | 52.82 | 5.06 |
,| Visit 1 | 44.91 | 22.91 | 62.99 | 31.2 | 3.61 | 1.27 | 5.47 | 4.2 | 1.98 | 2.06 | 0.72 | 0.96 | 2.62 | 0.31 | 1.81 | 0.5 | 23.72 | 0.54 | 11.78 | 0.9 | 23.29 | 0.59 |
,| Visit 2 | 13.64 | 32.93 | 23.26 | 59.52 | 7.85 | 1.26 | 5.73 | 9.22 | 7.07 | 1.85 | 1.51 | 1.45 | 1.77 | 0.25 | 2.88 | 1.22 | 29.45 | 0.4 | 20.93 | 0.13 | 30.39 | 0.72 |
,| Visit 3 | 13.9 | 32.22 | 24 | 59.66 | 13.97 | 2.02 | 14.7 | 2.23 | 9.31 | 2.7 | 2.14 | 2.32 | 2.64 | 0.67 | 4.03 | 1.49 | 49.96 | 0.47 | 41.53 | 0.14 | 40.4 | 1.3 |
Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients
baseline peripheral blood flow cytometric analysis in study participants (NCT02373098)
Timeframe: Baseline
| Intervention | absolute cell count (Mean) |
|---|
| CD3 abs | CD19 abs | NK abs | NKT abs | Hi CD16CD56 abs | CD4CD25 (CD3 gate) | Hi CD4CD25 (CD3 gate) |
|---|
| FTY720 | 1610.94 | 327.63 | 623.57 | 104.36 | 20.44 | 27.08 | 3.33 |
,| Healthy Controls | 2048.14 | 311.63 | 281.33 | 135.86 | 26.64 | 26.08 | 2.83 |
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
Blood samples were taken at baseline and measurements were performed before treatment of fingolimod. (NCT02373098)
Timeframe: Baseline
| Intervention | pg/ml (Mean) |
|---|
| CCL5 (RANTES) | IL-17A | CXCL13 | IL6 | IL8 | IL13 | IL23 | VLA4 | CXCL10=IP-10 (CXCR3 ligand) | CCL2=MCP-1 | IL4 | TNF alpha | IL22 |
|---|
| FTY720 | 404.31 | 1.06 | 139.68 | 66.53 | 3.57 | 0.3 | 3.04 | 0.58 | 18.18 | 62.89 | 2.36 | 1.06 | 22.41 |
,| Healthy Controls | 212.26 | 1.15 | 110.8 | 0.88 | 3.25 | 0.49 | 1.29 | 1.17 | 16.09 | 52.88 | 2.02 | 1.1 | 22.36 |
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
Baseline peripheral blood flow cytometric analyses in study participants evaluated by flow cytometry analysis. (NCT02373098)
Timeframe: Baseline
| Intervention | Percent of cells (Mean) |
|---|
| CD3 % | CD19 % | NK % | NKT % | Hi CD16CD56 % | CD3CD4 % (Lymphogate) | CD3CD8 % (Lymphogate) | CD3CD4 % (CD3 gate) | CD3CD8 % (CD3 gate) | CD4+IFNg+ (in CD4+) | CD4+IL17+ (in CD4+) | CD8+IFNg+ (in CD8+) | CD8+IL17+ (in CD8+) | IFNg+ (in CD4+CD25+) | IL17+ (in CD4+CD25+) | CD4+IL10+ (in CD4+) | CD4+IL4+ (in CD4+) | CD4-CD8-IL4+ (in CD4-CD8-) | CD8+IL10+ (in CD8+) | CD8+IL4+ % (in CD8+) | IL10+ (in CD4+CD25+) | IL4+ (in CD4+CD25+) | CD4+TNFa+ (in CD4+) | CD4+IL9+ (in CD4+) | CD8+TNFa+ (in CD8+) | CD8+IL9+ (in CD8+) | TNFa+ (in CD4+CD25+) | IL9+ (in CD4+CD25+) |
|---|
| FTY720 | 71.92 | 13.72 | 10.17 | 5.19 | 0.93 | 44.91 | 22.91 | 62.99 | 31.20 | 3.61 | 1.27 | 5.47 | 4.20 | 1.98 | 2.06 | 0.72 | 0.96 | 2.62 | 0.31 | 1.87 | 1.81 | 0.50 | 23.72 | 0.54 | 11.78 | 0.90 | 23.29 | 0.59 |
,| Healthy Controls | 76.52 | 11.57 | 11.04 | 5.65 | 1.05 | 41.19 | 23.23 | 57.38 | 35.11 | 7.42 | 1.23 | 16.45 | 1.71 | 7.1 | 2.35 | 1.64 | 1.44 | 1.31 | 0.52 | 5.64 | 2.57 | 1.88 | 46.86 | 0.22 | 35 | 0.14 | 52.82 | 5.06 |
Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
Peripheral blood chemokine cytokine levels measured by flow cytometry in healthy controls at baseline and in RRMS patients between visits during fingolimod treatment (NCT02373098)
Timeframe: Baseline, Month 3, Month 6
| Intervention | percent of cell count (Mean) |
|---|
| CD3 % | CD19 % | NK % | NKT % | Hi CD16CD56 % | CD8+IL4+ % (in CD8+) |
|---|
| Healthy Controls | 76.52 | 11.57 | 0.427 | 5.65 | 1.05 | 5.64 |
,| Visit 1 | 71.92 | 13.72 | 10.17 | 5.19 | 0.93 | 1.87 |
,| Visit 2 | 57.61 | 6.13 | 34.48 | 15.55 | 5.29 | 3.13 |
,| Visit 3 | 59.29 | 5.14 | 33.91 | 17.66 | 6.20 | 1.91 |
Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
Peripheral blood chemokine cytokine levels measured by flow cytometry during fingolimod treatment in healthy controls at baseline and in RRMS patients between visits (NCT02373098)
Timeframe: Baseline, Month 3, Month 6
| Intervention | pg/ml (Mean) |
|---|
| CD3 abs | CD19 abs | NK abs | NKT abs | Hi CD16CD56 abs | CD4CD25 (CD3 gate) | Hi CD4CD25 (CD3 gate) |
|---|
| Healthy Controls | 2048.14 | 311.63 | 281.33 | 135.86 | 26.64 | 26.08 | 2.83 |
,| Visit 1 | 1610.94 | 327.63 | 623.57 | 104.36 | 20.44 | 27.03 | 3.33 |
,| Visit 2 | 339.74 | 32.9 | 203.66 | 88.45 | 29.35 | 9.24 | 2.03 |
,| Visit 3 | 314.75 | 26.56 | 181.97 | 88.98 | 30.04 | 9.22 | 1.77 |
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
Change of serum cytokine and chemokine levels measured by ELISA in RRMS patients treated with fingolimod between visits (NCT02373098)
Timeframe: Baseline, month 3, month 6
| Intervention | pg/ml (Mean) |
|---|
| CXCL13=BLC | IL6 | IL8 | IL13 | CCL5= RANTES | IL23 | VLA4 | CXCL10=IP-10 (CXCR3 ligand) | CCL2=MCP-1 | IL4 | IL17A | TNF | IL22 |
|---|
| Visit 1 | 139.68 | 66.53 | 3.57 | 0.3 | 404.31 | 3.04 | 0.58 | 18.18 | 62.89 | 2.36 | 1.06 | 1.06 | 22.41 |
,| Visit 2 | 105.42 | 49.98 | 3.84 | 0.35 | 384.12 | 2.01 | 0.76 | 18.46 | 74.38 | 1.94 | 1.09 | 1.26 | 22.45 |
,| Visit 3 | 105.86 | 149.62 | 4.29 | 0.48 | 480.34 | 2.15 | 0.82 | 20.54 | 92.73 | 2.12 | 1.04 | 1.12 | 22.99 |
ALSFRS-R Total Score at Weeks 0, 2, 4 and 8
The ALSFRS-R is a quickly administered (5 minutes) ordinal rating scale (ratings 0-4) used to determine subjects' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, was closely associated with quality of life measures, and predicted survival. (NCT01786174)
Timeframe: Week 0, Week 2, Week 4 and Week 8
| Intervention | scores on a scale (Mean) |
|---|
| Week 0 | Week 2 | Week 4 | Week 8 |
|---|
| Gilenya (Fingolimod) | 38.60 | 38.15 | 38.03 | 36.74 |
,| Placebo | 38.60 | 38.29 | 37.88 | 37.10 |
Change in Slow Vital Capacity Score (SVC)
The vital capacity (VC) (percent of predicted normal) was determined using the slow VC method. Vital Capacity is the maximum amount of air a person can expel from the lungs after a maximum inhalation. A subject's VC depends on their age, sex and height. The value is recorded as a percent of predicted normal. (NCT01786174)
Timeframe: Week 0, Week 2, Week 4 and Week 8
| Intervention | Percentage of predicted max value (Mean) |
|---|
| Week 0 | Week 2 | Week 4 | Week 8 |
|---|
| Gilenya (Fingolimod) | 88.28 | 88.54 | 86.51 | 86.02 |
,| Placebo | 88.28 | 88.54 | 86.70 | 87.59 |
Forced Expiratory Volume in 1 Second (FEV1) / Slow Vital Capacity (SVC) Ratio
"Forced Expiratory Volume (FEV1): Forced Expiratory Volume (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.~Slow Vital Capacity (SVC): Vital Capacity is the maximum amount of air a person can expel from the lungs after a maximum inhalation. A subject's VC depends on their age, sex and height. The value is recorded as a percent of predicted normal." (NCT01786174)
Timeframe: Screening, Week 0, Week 2, and Week 4
| Intervention | Percentage of predicted max value (Mean) |
|---|
| Screening | Week 0 | Week 2 | Week 4 |
|---|
| Gilenya (Fingolimod) | 77.39 | 74.36 | 75.46 | 76.34 |
,| Placebo | 77.39 | 74.36 | 73.14 | 71.49 |
Forced Expiratory Volume in 1 Second (FEV1)
Forced Expiratory Volume (FEV1): Forced Expiratory Volume (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. (NCT01786174)
Timeframe: Screening, Week 0, Week 2, and Week 4
| Intervention | Percentage of predicted max value (Mean) |
|---|
| Screening | Week 0 | Week 2 | Week 4 |
|---|
| Gilenya (Fingolimod) | 84.70 | 81.93 | 81.19 | 80.38 |
,| Placebo | 84.70 | 81.93 | 80.30 | 78.16 |
Lymphocyte (T-Cell) Subset Trajectories
Gilenya (fingolimod) has been shown to successfully reduce circulating lymphocytes (a type of white blood cell) by blocking their egress (exit) from the lymph nodes. A secondary objective of the study is to quantify the effect of the treatment on circulating lymphocyte populations in patients with ALS. (NCT01786174)
Timeframe: Week 0, Week 2, and Week 4
| Intervention | 10^3/uL (Mean) |
|---|
| Week 0 | Week 2 | Week 4 |
|---|
| Gilenya (Fingolimod) | 1.751 | 0.580 | 0.499 |
,| Placebo | 1.751 | 1.732 | 1.822 |
Cognition Change - BACS
The Brief Assessment of Cognition in Schizophrenia (BACS) is a battery specifically designed to measure treatment-related changes in cognition by utilizing 6 tasks, and has alternate forms, thus minimizing practice effects. Each task generates a raw score (with a higher score indicating better performance): verbal memory 0-75; digit sequencing 0-28; token motor task 0-100; semantic&letter fluency 0-148; symbol coding 0-110; and tower of London 0-22. The raw scores are used to generate a composite score that is calculated by summing t-scores derived by comparisons with a normative sample of 404 healthy controls. The six brief assessments' t-scores, are summed, and averaged to provide a composite t-score. The composite score min and max are between -43 and 100. A higher score indicating better cognitive performance. (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | score on a scale (Mean) |
|---|
| BACS Composite Score - Baseline | BACS Composite Score - 4 weeks | BACS Composite Score - 8 weeks |
|---|
| Fingolimod | 25.17 | 27.67 | 31.13 |
,| Placebo | 30.95 | 32.10 | 33.50 |
Cognition Change - Trails B
The Trail Making Test-Part B (Trails B) is a measure of visual attention and task switching. The task requires a subject to 'connect-the-dots' of 25 consecutive targets on a sheet of paper. In Part B version the subject alternates between numbers and letters (1, A, 2, B, etc.) The goal of the test is for the subject is to finish part B as quickly as possible, the time taken to complete the test is used as the primary performance metric. The score is the number of seconds it took to complete the test. (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | seconds (Mean) |
|---|
| Trails B - Baseline | Trails B - 4 weeks | Trails B - 8 weeks |
|---|
| Fingolimod | 108.00 | 97.88 | 84.53 |
,| Placebo | 123.64 | 100.60 | 102.33 |
Levels of Lymphocyte
To determine the safety of fingolimod, as measured by the absolute lymphocyte count (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | 10^3 lymphocytes/uL (Mean) |
|---|
| Absolute lymphocyte count - Baseline | Absolute lymphocyte count - 4 weeks | Absolute lymphocyte count - 8 weeks |
|---|
| Fingolimod | 1.99 | 0.44 | 0.49 |
,| Placebo | 1.97 | 1.94 | 2.00 |
Negative Symptom Change - PANSS
The Positive and Negative Syndrome Scale (PANSS) is a semi-structured interview, containing 30 items that assess symptoms of psychotic disorders including positive, negative, and general psychopathology symptoms. Positive symptoms are rated on 7 items, negative symptoms are rated on 7 items, and general psychopathology on 16 items. Scores for each item range from 1=absent to 7=extreme. Positive, negative, and general psychopathology symptoms can each respectively render total scores. Positive total scores ranging from 7-49, negative total scores ranging from 7-49, and general psychopathology scores ranging from 16-112. When all items are summed together a total score is generated. Total scores for all items range from 30-210, a lower score reflecting fewer symptoms. (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | score on a scale (Mean) |
|---|
| PANSS Negative Score - Baseline | PANSS Negative Score - 4 weeks | PANSS Negative Score - 8 weeks |
|---|
| Fingolimod | 15.00 | 13.89 | 15.44 |
,| Placebo | 16.59 | 14.80 | 15.06 |
Plasma Cytokines Levels - IFNgamma
To assess IFNgamma plasma cytokines levels changes in participants taking fingolimod versus placebo (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | pg/ml (Mean) |
|---|
| IFNgamma - Baseline | IFNgamma - 4 weeks | IFNgamma - 8 weeks |
|---|
| Fingolimod | 5.32 | 4.61 | 4.32 |
,| Placebo | 8.32 | 4.95 | 5.62 |
Plasma Cytokines Levels - IL-10
To assess IL-10 plasma cytokines levels changes in participants taking fingolimod versus placebo (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | pg/ml (Mean) |
|---|
| IL10 - Baseline | IL10 - 4 weeks | IL10 - 8 weeks |
|---|
| Fingolimod | 16.11 | 15.50 | 16.28 |
,| Placebo | 11.94 | 9.23 | 10.42 |
Plasma Cytokines Levels - IL-17A
To assess IL-17A plasma cytokines levels changes in participants taking fingolimod versus placebo (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | pg/ml (Mean) |
|---|
| IL17A - Baseline | IL17A - 4 weeks | IL17A - 8 weeks |
|---|
| Fingolimod | 3.09 | 2.58 | 2.58 |
,| Placebo | 3.72 | 2.43 | 2.69 |
Plasma Cytokines Levels - IL-1BETA
To assess IL-1BETA plasma cytokines levels changes in participants taking fingolimod versus placebo (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | pg/ml (Mean) |
|---|
| IL1BETA - Baseline | IL1BETA - 4 weeks | IL1BETA - 8 weeks |
|---|
| Fingolimod | 0.87 | 0.81 | 0.82 |
,| Placebo | 0.69 | 0.72 | 0.74 |
Plasma Cytokines Levels - IL-2
To assess IL-2 plasma cytokines levels changes in participants taking fingolimod versus placebo (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | pg/ml (Mean) |
|---|
| IL2 - Baseline | IL2 - 4 weeks | IL2 - 8 weeks |
|---|
| Fingolimod | 1.74 | 1.96 | 1.77 |
,| Placebo | 1.27 | 1.20 | 1.20 |
Plasma Cytokines Levels - IL-4
To assess IL-4 plasma cytokines levels changes in participants taking fingolimod versus placebo (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | pg/ml (Mean) |
|---|
| IL4 - Baseline | IL4 - 4 weeks | IL4 - 8 weeks |
|---|
| Fingolimod | 30.99 | 27.40 | 24.20 |
,| Placebo | 30.74 | 31.34 | 32.16 |
Plasma Cytokines Levels - IL-6
To assess IL-6 plasma cytokines levels changes in participants taking fingolimod versus placebo (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | pg/ml (Mean) |
|---|
| IL6 - Baseline | IL6 - 4 weeks | IL6 - 8 weeks |
|---|
| Fingolimod | 2.15 | 2.22 | 2.16 |
,| Placebo | 1.90 | 1.81 | 1.96 |
Plasma Cytokines Levels - IL-8
To assess IL-8 plasma cytokines levels changes in participants taking fingolimod versus placebo (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | pg/ml (Mean) |
|---|
| IL8 - Baseline | IL8 - 4 weeks | IL8 - 8 weeks |
|---|
| Fingolimod | 4.29 | 3.81 | 4.18 |
,| Placebo | 3.83 | 3.69 | 3.69 |
Plasma Cytokines Levels - TNFa
To assess TNFa plasma cytokines levels changes in participants taking fingolimod versus placebo (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | pg/ml (Mean) |
|---|
| TNFa - Baseline | TNFa - 4 weeks | TNFa - 8 weeks |
|---|
| Fingolimod | 2.11 | 2.02 | 2.00 |
,| Placebo | 1.76 | 1.86 | 1.61 |
Positive Symptom Change - PANSS
The Positive and Negative Syndrome Scale (PANSS) is a semi-structured interview, containing 30 items that assess symptoms of psychotic disorders including positive, negative, and general psychopathology symptoms. Positive symptoms are rated on 7 items, negative symptoms are rated on 7 items, and general psychopathology on 16 items. Scores for each item range from 1=absent to 7=extreme. Positive, negative, and general psychopathology symptoms can each respectively render total scores. Positive total scores ranging from 7-49, negative total scores ranging from 7-49, and general psychopathology scores ranging from 16-112. When all items are summed together a total score is generated. Total scores for all items range from 30-210, a lower score reflecting fewer symptoms. (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | score on a scale (Mean) |
|---|
| PANSS Positive Score - Baseline | PANSS Positive Score - 4 weeks | PANSS Positive Score - 8 weeks |
|---|
| Fingolimod | 10.83 | 11.89 | 10.06 |
,| Placebo | 13.64 | 14.00 | 13.06 |
QTcB Change
To determine the safety of fingolimod, as measured by the electrocardiogram (ECG) QT interval corrected by Bazett's (QTcB) value. (NCT01779700)
Timeframe: Screening, Day 0, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 84, Day 112
| Intervention | ms (Mean) |
|---|
| QTcB - Screening | QTcB - Day 0 | QTcB - Day 7 | QTcB - Day 14 | QTcB - Day 21 | QTcB - Day 28 | QTcB - Day 35 | QTcB - Day 42 | QTcB - Day 49 | QTcB - Day 56 | QTcB - Day 84 | QTcB - Day 112 |
|---|
| Fingolimod | 416.50 | 418.39 | 415.50 | 418.28 | 419.67 | 424.06 | 426.18 | 425.53 | 420.79 | 420.67 | 421.50 | 419.67 |
,| Placebo | 416.41 | 423.27 | 417.00 | 420.15 | 412.00 | 415.74 | 419.00 | 414.33 | 413.53 | 418.41 | 420.68 | 418.58 |
Symptom Changes - PANSS Total Score
The Positive and Negative Syndrome Scale (PANSS) is a semi-structured interview, containing 30 items that assess symptoms of psychotic disorders including positive, negative, and general psychopathology symptoms. Positive symptoms are rated on 7 items, negative symptoms are rated on 7 items, and general psychopathology on 16 items. Scores for each item range from 1=absent to 7=extreme. Positive, negative, and general psychopathology symptoms can each respectively render total scores. Positive total scores ranging from 7-49, negative total scores ranging from 7-49, and general psychopathology scores ranging from 16-112. When all items are summed together a total score is generated. Total scores for all items range from 30-210, a lower score reflecting fewer symptoms. (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | score on a scale (Mean) |
|---|
| PANSS Total Score - Baseline | PANSS Total Score - 4 weeks | PANSS Total Score - 8 weeks |
|---|
| Fingolimod | 48.89 | 49.78 | 49.06 |
,| Placebo | 56.50 | 53.60 | 54.94 |
Verbal Memory - BACS
The Brief Assessment of Cognition in Schizophrenia (BACS) is a battery specifically designed to measure treatment-related changes in cognition. The BACS utilizes 6 tasks, and has alternate forms, thus minimizing practice effects. Each task generates a raw score (with a higher score indicating better performance): verbal memory 0-75; digit sequencing 0-28; token motor task 0-100; semantic&letter fluency 0-148; symbol coding 0-110; and tower of London 0-22. The raw scores are used to generate a composite score that is calculated by summing t-scores derived by comparisons with a normative sample of 404 healthy controls. The six brief assessments' t-scores, are summed, and averaged to provide a composite t-score. The composite score min and max are between -43 and 100. A higher score indicating better cognitive performance. (NCT01779700)
Timeframe: Baseline, 4 weeks, 8 weeks
| Intervention | score on a scale (Mean) |
|---|
| BACS Verbal Memory - Baseline | BACS Verbal Memory - 4 weeks | BACS Verbal Memory - 8 weeks |
|---|
| Fingolimod | 30.89 | 33.50 | 34.69 |
,| Placebo | 37.45 | 35.45 | 36.11 |
Number of Participants With Bradyarrhythmic Electrocardiogram (ECG) Events
The number of participants with bradyarrhythmic electrocardiogram (ECG) events was assessed. Bradyarrhythmic ECG events are defined as QTc Fridericia time > 450 ms for males and > 470 ms for females. (NCT01585298)
Timeframe: up to day 7
| Intervention | Participants (Number) |
|---|
| Fingolimod | 26 |
Number of Patients With Heart Rate Below 45 Beats Per Minute (BPM)
Number of patients with heart rate below 45 beats bpm in ECG during first dose observation (NCT01585298)
Timeframe: baseline during 6 hour monitoring post dose
| Intervention | Participants (Number) |
|---|
| Fingolimod | 63 |
Number of Participants With Prolonged QTc Interval (Friderica)
"Number of patients with conduction abnormalities such as QT prolongation, first degree AV block during treatment initiation.~The QT interval is a period between the activation and the regeneration of ventricular contraction. A prolonged QT interval can be a potential marker of cardiac arrhythmias.~Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients." (NCT01585298)
Timeframe: baseline post-dose
| Intervention | Participants (Number) |
|---|
| Female, QTcFridericia Interval > 470 ms | Male, QTcF Interval > 450 ms |
|---|
| Fingolimod | 7 | 6 |
Number of Patients With Cardiac Adverse Events
The number of participants with the occurrence of subsequent cardiac adverse events (AEs) and serious cardiac AEs during study was assessed. Cardiac events were defined as the following Medical Dictionary for Regulatory Activities (MedDRA) preferred terms: angina pectoris, chest discomfort, dizziness, dyspnoea, dyspnoea exertional, fatigue, palpitations, syncope, vertigo, vertigo positional and vision blurred. (NCT01585298)
Timeframe: 7 days
| Intervention | Participants (Number) |
|---|
| Cardiac events | Serious cardiac AEs |
|---|
| Fingolimod | 489 | 9 |
Participants With 2nd or 3rd Degree Atrioventricular (AV) Block
AV Blocks/Heart block is an abnormal heart rhythm where the heart beats too slowly; the electrical signals that tell the heart to contract are partially intermittent (Type 2:1) or slowed (1st and 2nd degree) or blocked (3rd degree) between the upper chambers (atria) and the lower chambers (ventricles). In 2nd degree AV Blocks, electrical impulses are intermittent (type 2:1) or delayed w/ each subsequent heartbeat (Mobitz type I) until a beat fails to reach the ventricles entirely. This type of block often is physiologic and observed in a highly relaxed state & during sleep. In 2nd degree AV Blocks type II, the atria electrical impulses are unable to reach the ventricles, a more serious condition. In 3rd degree AV Blocks (complete heart block), none of the electrical impulses reach either the atria or the ventricles. Patients can experience simultaneously both types of 2nd or 3rd degree AV Blocks without any symptoms. (NCT01585298)
Timeframe: baseline, during 6 hour monitoring post first dose observation
| Intervention | Participants (Number) |
|---|
| Any AV block ll degree or higher | AV block ll degree: Mobitz type I degree | AV block II degree: Mobitz type II degree | AV block II degree: 2:1 | AV block III degree |
|---|
| Fingolimod | 120 | 117 | 0 | 43 | 1 |
Time to First Confirmed Worsening on the Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale
Confirmed worsening in CIDP was measured by the adjusted INCAT Disability Scale. The adjusted INCAT disability scale measures arm disability and leg disability. For arm disability the scale ranges from 0 (no upper limb problems) to 5 (inability to use either arm for any purposeful movement). The leg disability scale ranges from 0 (walking not affected) to 5 (restricted to wheelchair, unable to stand and walk a few steps with help). The total adjusted INCAT disability score is calculated by the sum of the arm and leg disability scores where the total score ranges from 0 to 10. A confirmed worsening was defined as an increase by 1 or more points on the adjusted INCAT disability scale from the value at baseline. (NCT01625182)
Timeframe: Month 12
| Intervention | Days (Median) |
|---|
| Fingolimod (FTY720) | 721.0 |
| Placebo | 540.0 |
Change From Baseline for Grip Strength, Dominant Hand
Grip strength measurements were done using a vigorimeter. With this device, the pressure in the bulb exercised by the participant was registered on a manometer via a rubber junction tube. Both the dominant and non-dominant hands were tested. A negative change from baseline indicates deterioration. (NCT01625182)
Timeframe: baseline, Month 6, Month 12
| Intervention | kPa (Least Squares Mean) |
|---|
| Month 6 | Month 12 |
|---|
| Fingolimod (FTY720) | -2.6 | -0.8 |
,| Placebo | -3.8 | -3.9 |
Change From Baseline for Grip Strength, Non-dominant Hand
Grip strength measurements were done using a vigorimeter. With this device, the pressure in the bulb exercised by the participant was registered on a manometer via a rubber junction tube. Both the dominant and non-dominant hands were tested. A negative change from baseline indicates deterioration. (NCT01625182)
Timeframe: baseline, Month 6, Month 12
| Intervention | kPa (Least Squares Mean) |
|---|
| Month 6 | Month 12 |
|---|
| Fingolimod (FTY720) | -2.7 | -1.2 |
,| Placebo | -6.1 | -5.0 |
Change From Baseline for Rasch-Built Linearly Weighted Overall Disability Scale (R-ODS)
This questionnaire was constructed using the patients' perception of their ability to perform daily and social activities. The questionnaire comprises 24 items ranging from ability to read a book or newspaper (as the easiest item to accomplish) to ability to run (most difficult item to accomplish). The obtained raw summed score was translated subsequently to a convenient centile metric score ranging from 0 (most severe disability) to 100 (no disability at all). A higher score indicated a better health status. A negative change from baseline indicates deterioration. (NCT01625182)
Timeframe: baseline, Month 6, Month 12
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Month 6 | Month 12 |
|---|
| Fingolimod (FTY720) | -6.4 | -5.7 |
,| Placebo | -5.5 | -5.1 |
Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline)
Lesions will be measured by MRIs and the number of active (new or newly enlarging) T2 lesions will be calculated for 24 weeks from baseline. (NCT01499667)
Timeframe: Baseline up to 24 weeks
| Intervention | Count of Active T2 Lesions (Mean) |
|---|
| 8-week Washout + Fingolimod (FTY720) | 3.2 |
| 12-week Washout + Fingolimod (FTY720) | 4.4 |
| 16-week Washout + Fingolimod (FTY720) | 7.7 |
Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment
Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated for first 8 weeks of fingolimod treatment. (NCT01499667)
Timeframe: Number of active T2 lesions during 8 wks of fingolimod treatment
| Intervention | Count of Active T2 Lesions (Mean) |
|---|
| 8-week Washout + Fingolimod (FTY720) | 1.5 |
| 12-week Washout + Fingolimod (FTY720) | 2.1 |
| 16-week Washout + Fingolimod (FTY720) | 4.2 |
Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment
Active lesions were measured on brain MRI scans, performed at week 8, compared to the prior scan. The primary variable was analyzed by fitting a negative binomial regression model adjusted for washout group. (NCT01499667)
Timeframe: Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment
| Intervention | Count of Active T2 Lesions (Mean) |
|---|
| 8-week Washout + Fingolimod (FTY720) | 2.1 |
| 12-week Washout + Fingolimod (FTY720) | 1.7 |
| 16-week Washout + Fingolimod (FTY720) | 8.2 |
Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment
Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment. (NCT01499667)
Timeframe: 8, 12 and 16 weeks (number of active T2 lesions during the washout period only)
| Intervention | Count of active T2 lesions (Mean) |
|---|
| 8-week Washout + Fingolimod (FTY720) | 0.4 |
| 12-week Washout + Fingolimod (FTY720) | 2.1 |
| 16-week Washout + Fingolimod (FTY720) | 3.6 |
Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group
Kurtzke's Expanded Disability Status Scale (EDSS) measures the changes in neurologic impairment, either chronic (progression over time), or acute (MS relapses). The EDSS steps range from 0 (normal) to 10 (death due to MS). Relapse severity is assessed based on severity of neurologic impairment as evaluated using the EDSS. (NCT01499667)
Timeframe: Baseline to week 16 and week 32
| Intervention | Units on a scale (Mean) |
|---|
| Week 16 (n=40, 33, 39) | Week 32 (n= 40,30,39) |
|---|
| 12-week Washout + Fingolimod (FTY720) | -0.03 | -0.13 |
,| 16-week Washout + Fingolimod (FTY720) | 0.23 | 0.08 |
,| 8-week Washout + Fingolimod (FTY720) | 0.11 | 0.11 |
Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion
Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans (NCT01499667)
Timeframe: 8 weeks and 24 weeks
| Intervention | Number of Gd enhanced T1 Lesions (Mean) |
|---|
| Week 8 (n=1,1,0) | Week 24 (n=10,12,21) |
|---|
| 12-week Washout + Fingolimod (FTY720) | 2.0 | 3.4 |
,| 16-week Washout + Fingolimod (FTY720) | NA | 3.6 |
,| 8-week Washout + Fingolimod (FTY720) | 25.0 | 6.3 |
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment
Adverse events were summarized by the number of patients having any adverse event overall. (NCT01499667)
Timeframe: Baseline to maximum of 16 weeks
| Intervention | participants (Number) |
|---|
| Any Adverse Events | Serious Adverse Events | Death |
|---|
| 12-week Washout + Fingolimod (FTY720) | 20 | 5 | 0 |
,| 16-week Washout + Fingolimod (FTY720) | 28 | 3 | 0 |
,| 8-week Washout + Fingolimod (FTY720) | 35 | 2 | 0 |
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period
Adverse events were summarized by the number of patients having any adverse event overall. (NCT01499667)
Timeframe: Baseline to maximum of 16 weeks
| Intervention | participants (Number) |
|---|
| Any Adverse Events | Serious Adverse Events | Death |
|---|
| 12-week Washout + Fingolimod (FTY720) | 12 | 0 | 0 |
,| 16-week Washout + Fingolimod (FTY720) | 25 | 1 | 0 |
,| 8-week Washout + Fingolimod (FTY720) | 13 | 0 | 0 |
Annual Relapse Rate (ARR)
ARR = 365 days * number of relapses / total days taking the study medication. (NCT01498887)
Timeframe: 12 months
| Intervention | Relapses per year (Mean) |
|---|
| Naive or de Novo Participants | 0.290 |
| Previously Treated With First-line DMTs Participants | 0.354 |
Change From Baseline in Cerebral Volume
Cerebral volume was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement. (NCT01498887)
Timeframe: baseline, 12 months
| Intervention | Percent change (Mean) |
|---|
| Naive or de Novo Participants | -0.595 |
| Previously Treated With First-line DMTs Participants | -0.387 |
Change From Baseline in Expanded Disability Status Scale (EDSS) Score
The EDSS is an ordinal clinical rating scale ranging from a total score of 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. A negative change from baseline indicates improvement. (NCT01498887)
Timeframe: baseline, 12 months
| Intervention | score on a scale (Mean) |
|---|
| Naive or de Novo Participants | 0.000 |
| Previously Treated With First-line DMTs Participants | -0.077 |
Mean Number of T2 Active Lesions
The mean number of new or enlarged T2 active lesions was assessed by MRI. (NCT01498887)
Timeframe: 12 months
| Intervention | T2 lesions (Mean) |
|---|
| Naive or de Novo Participants | 2.0 |
| Previously Treated With First-line DMTs Participants | 1.6 |
Percentage of Relapse-free Participants
Relapse-free participants were defined as participants who experienced no new neurological symptom or worsening of an existing one (relapses) during the 12-month treatment period with 0.5 mg fingolimod. (NCT01498887)
Timeframe: 12 months
| Intervention | Percent (Number) |
|---|
| Naive or de Novo Participants | 71.89 |
| Previously Treated With First-line DMTs Participants | 66.67 |
Time to First Relapse
Time to first relapse was defined as the time from the first day of treatment to the first day of a new neurological symptom or worsening of an existing one. (NCT01498887)
Timeframe: first day of treatment to the first day of a new neurological symptom or worsening of an existing one, up to 12 months
| Intervention | months (Median) |
|---|
| Naive or de Novo Participants | NA |
| Previously Treated With First-line DMTs Participants | NA |
Percentage of Participants With Mild, Moderate or Severe Relapse
The investigator classified a relapse as moderate-severe if oral or intravenous (IV) treatment (according to the local clinical practice) with steroids and/or hospitalization was needed. If neither oral nor IV treatment with steroids nor hospitalization was needed, the relapse was considered as mild. (NCT01498887)
Timeframe: 12 months
| Intervention | Percentage of participants (Number) |
|---|
| Mild | Moderate | Severe |
|---|
| Naive or de Novo Participants | 42.55 | 57.45 | 0.00 |
,| Previously Treated With First-line DMTs Participants | 38.46 | 56.41 | 5.13 |
Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death
"In this analysis patients with all (serious and non-serious) adverse events, and death were reported.~See Safety Section." (NCT01436643)
Timeframe: 21 weeks
| Intervention | Participants (Number) |
|---|
| Any Adverse Event | Death | Serious Adverse Event |
|---|
| Citalopram and Fingolimod | 12 | 0 | 1 |
,| Fingolimod | 15 | 0 | 1 |
,| Fluoxetine and Fingolimod | 11 | 0 | 0 |
,| Venlafaxine and Fingolimod | 12 | 0 | 1 |
Change From Baseline to Month 36 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)
The primary endpoint was the change, i.e. the absolute difference, in average RNFL thickness from baseline to month 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT). (NCT01705236)
Timeframe: Baseline, month 36
| Intervention | micrometer (Mean) |
|---|
| Fingolimod - Longitudinal Assessment | -1.5 |
Change From Baseline to Month 12 and 24 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)
Change from baseline in average RNFL thickness to months 12 and 24 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT). (NCT01705236)
Timeframe: Baseline, month 12, month 24
| Intervention | micrometer (Mean) |
|---|
| Change from baseline to month 12 | Change from baseline to month 24 |
|---|
| Fingolimod - Longitudinal Assessment | -0.8 | -1.1 |
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Change from baseline in average quadrant RNFL thickness to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average quadrant RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT). Quadrant RNFL thickness were: Nasal-inferior; nasal-superior; temporal-inferior; temporal-superior. (NCT01705236)
Timeframe: Baseline, month 12, month 24, month 36
| Intervention | micrometer (Mean) |
|---|
| Nasal-superior RNFL thickness: month 12 | Nasal-superior RNFL thickness: month 24 | Nasal-superior RNFL thickness: month 36 | Nasal-inferior RNFL thickness: month 12 | Nasal-inferior RNFL thickness: month 24 | Nasal-inferior RNFL thickness: month 36 | Temporal-inferior RNFL thickness: month 12 | Temporal-inferior RNFL thickness: month 24 | Temporal-inferior RNFL thickness: month 36 | Temporal-superior RNFL thickness: month 12 | Temporal-superior RNFL thickness: month 24 | Temporal-superior RNFL thickness: month 36 |
|---|
| Fingolimod - Longitudinal Assessment | 0.5 | -0.4 | -0.7 | -1.2 | -1.6 | -2.1 | -1.2 | -1.6 | -2.3 | -0.5 | -0.4 | -1.1 |
Change From Baseline to Month 12, 24 and 36 in Ganglion Cell Inner Plexiform (GCIP)
"Change from baseline in GCIP to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS).~The change in Ganglion cell layer thickness (GCLT) had been defined as secondary endpoint in the protocol, but OCT measured the GCIP instead. This was done because both layers were not clearly separable by OCT. GCIP was calculated as mean of the inner sectors (nasal, superior, temporal, and inferior) and declared as usual parameter instead. This change was introduced prior to data base lock, but the derivation of GCIP was corrected after data base lock." (NCT01705236)
Timeframe: Baseline, month 12, month 24, month 36
| Intervention | micrometer (Mean) |
|---|
| Change from baseline to month 12 | Change from baseline to month 24 | Change from baseline to month 36 |
|---|
| Fingolimod - Longitudinal Assessment | -0.49 | -0.42 | -0.46 |
Change From Baseline to Month 12, 24 and 36 in Total Macular Volume (TMV)
Change from baseline in TMV to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS). (NCT01705236)
Timeframe: 12, 24 and 36 months
| Intervention | Cubic millimeter (Mean) |
|---|
| Change from baseline to month 12 | Change from baseline to month 24 | Change from baseline to month 36 |
|---|
| Fingolimod - Longitudinal Assessment | -0.03 | -0.04 | -0.06 |
Number of Participants With Adverse Events
Number of participants with adverse events and specifically macular edema. (NCT01705236)
Timeframe: 36 months
| Intervention | Participants (Count of Participants) |
|---|
| No. of subjects with any AE | No. of subjects with macular edema |
|---|
| Fingolimod - Longitudinal Assessment | 80 | 0 |
Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36).
The SF-36v2 is a validated health-related quality of life instrument used in numerous disease states, including MS. It is a self-administered survey that measures 8 domains of health including: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems and general mental health. Additionally, two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). If half or more questions within a domain were answered, then a score was calculated for that domain. Otherwise, the patient score for that domain was set to missing. If the patient was missing any 1 of the 8 scale scores, then the physical and mental component scores were set to missing. An algorithm was used to create a score from 0 to 100 for each domain score and component score. A positive change from baseline indicates improvement. (NCT01578330)
Timeframe: Month 1
| Intervention | score on scale (Mean) |
|---|
| Physical Function | Physical Role | Pain | General Health | Vitality | Social Function | Emotional Role | Mental Health |
|---|
| Fingolimod, FTY720 | 59.7 | 53.6 | 61.7 | 47.8 | 28.9 | 61.8 | 48.4 | 31.5 |
Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36).
The SF-36v2 is a validated health-related quality of life instrument used in numerous disease states, including MS. It is a self-administered survey that measures 8 domains of health including: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems and general mental health. Additionally, two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). If half or more questions within a domain were answered, then a score was calculated for that domain. Otherwise, the patient score for that domain was set to missing. If the patient was missing any 1 of the 8 scale scores, then the physical and mental component scores were set to missing. An algorithm was used to create a score from 0 to 100 for each domain score and component score. A positive change from baseline indicates improvement. (NCT01578330)
Timeframe: Month 12
| Intervention | score on scale (Mean) |
|---|
| Physical Function (n=31) | Physical Role (n=32) | Pain (n=32) | General Health (n=31) | Vitality (n=32) | Social Function (n=32) | Emotional Role (n=31) | Mental Health (n=32) |
|---|
| Fingolimod, FTY720 | 59.5 | 46.9 | 65.9 | 50.8 | 33.1 | 65.8 | 52.7 | 36.3 |
Mean Patient-reported Health-related Quality-of-life With Fingolimod (Short Form Health Survey: SF-36).
The SF-36v2 is a validated health-related quality of life instrument used in numerous disease states, including MS. It is a self-administered survey that measures 8 domains of health including: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems and general mental health. Additionally, two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). If half or more questions within a domain were answered, then a score was calculated for that domain. Otherwise, the patient score for that domain was set to missing. If the patient was missing any 1 of the 8 scale scores, then the physical and mental component scores were set to missing. An algorithm was used to create a score from 0 to 100 for each domain score and component score. A positive change from baseline indicates improvement. (NCT01578330)
Timeframe: Month 6
| Intervention | score on scale (Mean) |
|---|
| Physical Function (n=33) | Physical Role (n=34) | Pain (n=34) | General Health (n=33) | Vitality (n=34) | Social Function (n=34) | Emotional Role (n=34) | Mental Health (n=34) |
|---|
| Fingolimod, FTY720 | 57.9 | 47.8 | 62.6 | 48.5 | 35.2 | 60.6 | 54.8 | 36.5 |
Mean Patient-Reported Treatment Satisfaction Questionnaire for Medication Scores (TSQM-9)
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. The lowest possible score (1 for each item and 3 for all 3 subscales) was subtracted from the composite score and divided by the greatest possible score range. The greatest range was (7-1) X 3 items = 18 for the effectiveness and convenience, and (5-1) x 3 items = 12 for global satisfaction. This provided a transformed score between 0 and 1 that was then multiplied by 100. A positive change from baseline indicates improvement. (NCT01578330)
Timeframe: Baseline and month 12
| Intervention | Scores on a scale (Mean) |
|---|
| Baseline (n=34) | Month 12 (n=32) |
|---|
| Fingolimod, FTY720 | 32.0 | 44.7 |
Number (%) of Patients With AE of Special Interest Including Bradyarrhythmia, BP Increase, Liver Transaminase Elevations, Infections , Macula Oedema.
The incidence of events in special areas of safety interest (including bradyarrhythmias, BP increase, liver function, infections and macular oedema) were assessed by the nature and frequency of AE reporting. These areas of special interest have been identified and potential risks of fingolimod based on knowledge from clinical trials and post-marketing reporting. (NCT01497262)
Timeframe: 4 months
| Intervention | Percent of Participants (Number) |
|---|
| Bradyarrhythmias | Blood pressure increase | Hypertension | Liver Transaminase evaluations | Infections | Macula Oedema |
|---|
| Fingolimod 0.5 mg | 8.6 | 0.6 | 2.5 | 3.7 | 28.4 | 0 |
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Any Adverse Event was defined as occurrence of any symptom regardless of intensity grade, Serious Adverse Event (SAEs) assessed as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in persistent or significant disability/incapacity (NCT01497262)
Timeframe: 28 weeks
| Intervention | Participants (Number) |
|---|
| Adverse Events (AE) | Serious Adverse Event (SAE) | Deaths |
|---|
| Fingolimod 0.5 mg | 100 | 12 | 0 |
Participant Retention Rate Over 12 Months
Comparison effectiveness of fingolimod versus approved first-line disease modifying therapies by measuring the rate of participant retention on randomized treatment over a 12-month period (Full analysis set) (NCT01623596)
Timeframe: at 12 months
| Intervention | participants (Number) |
|---|
| Fingolimod | 352 |
| Disease Modifying Therapy (MS-DMT) | 125 |
Change From Baseline of Symbol Digit Modalities Test (SDMT) Scores (Oral Test) by Visit (Randomized Treatment / Randomized Phase)
"Summary statistics Compare cognitive impairment measured by Symbol Digit Modalities Test (SDMT) scores. The SDMT score and its change from baseline value were summarized by visit. For the change from baseline values at each visit, ANCOVA adjusted for treatment naivety, corresponding baseline values, and age was performed for treatment comparisons~The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution.~NOTE: Higher scores indicate better performance." (NCT01623596)
Timeframe: baseline, 6 months, 12 months, and Last assessment which is either at Month 12 or at early discontinuation
| Intervention | SDMT score (Mean) |
|---|
| Baseline (n=76,70) | Change at 6 months (n=70,64) | Change at 12 months (n=58, 18) | Change at Last assessment (n=73, 65) |
|---|
| Disease Modifying Therapy (MS-DMT) | 51.60 | 0.20 | 1.40 | 0.40 |
,| Fingolimod | 52.00 | 2.20 | 3.20 | 3.30 |
Change From Baseline of Symbol Digit Modalities Test (SDMT) Scores (Written Test) by Visit (Randomized Treatment / Randomized Phase)
"Summary statistics Compare cognitive impairment measured by Symbol Digit Modalities Test (SDMT) scores. The SDMT score and its change from baseline value were summarized by visit. For the change from baseline values at each visit, ANCOVA adjusted for treatment naivety, corresponding baseline values, and age was performed for treatment comparisons~The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution.~NOTE: Higher scores indicate better performance." (NCT01623596)
Timeframe: baseline, 6 months, 12 months, Last assessment which is either at Month 12 or at early discontinuation
| Intervention | SDMT score (Mean) |
|---|
| Baseline (n=355,348) | Change at 6 months (n=339,322) | Change at 12 months (n=282,105) | Change at Last assessment (n=342, 324) |
|---|
| Disease Modifying Therapy (MS-DMT) | 48.50 | 0.70 | 0.40 | 0.70 |
,| Fingolimod | 48.90 | -0.50 | 0.70 | 0.80 |
Number of Satisfied Participants Per Medication Satisfaction Questionnaire (MSQ) Score
"Summary statistics for Medication Satisfaction Questionnaire[Question: Overall, how satisfied are you with your current medication?] (Randomized treatment / randomized phase): Fingolimod vs MS-DMT" (NCT01623596)
Timeframe: Baseline, 1 month, 3 months, 6 months, 9 months, at 12 months & Last assessment during randomized phase which is either at Month 12 or at early discontinuation
| Intervention | participants (Number) |
|---|
| Baseline, Extremely dissatisfied | Baseline, Very dissatisfied | Baseline, Somewhat dissatisfied | Baseline, Neither dissatisfied nor satisfied | Baseline, Somewhat satisfied | Baseline, Very satisfied | Baseline, Extremely satisfied | Baseline, Missing | 1 month, Extremely dissatisfied | 1 month, Very dissatisfied | 1 month, Somewhat dissatisfied | 1 month, Neither dissatisfied nor satisfied | 1 month, Somewhat satisfied | 1 month, Very satisfied | 1 month, Extremely satisfied | 1 month, Missing | 3 months, Extremely dissatisfied | 3 months, Very dissatisfied | 3 months, Somewhat dissatisfied | 3 months, Neither dissatisfied nor satisfied | 3 months, Somewhat satisfied | 3 months, Very satisfied | 3 months, Extremely satisfied | 3 months, Missing | 6 months, Extremely dissatisfied | 6 months, Very dissatisfied | 6 months, Somewhat dissatisfied | 6 months, Neither dissatisfied nor satisfied | 6 months, Somewhat satisfied | 6 months, Very satisfied | 6 months, Extremely satisfied | 6 months, Missing | 9 months, Extremely dissatisfied | 9 months, Very dissatisfied | 9 months, Somewhat dissatisfied | 9 months, Neither dissatisfied nor satisfied | 9 months, Somewhat satisfied | 9 months, Very satisfied | 9 months, Extremely satisfied | 9 months, Missing | 12 months, Extremely dissatisfied | 12 months, Very dissatisfied | 12 months, Somewhat dissatisfied | 12 months, Neither dissatisfied nor satisfied | 12 months, Somewhat satisfied | 12 months, Very satisfied | 12 months, Extremely satisfied | 12 months, Missing | Last assessment, Extremely dissatisfied | Last assessment, Very dissatisfied | Last assessment, Somewhat dissatisfied | Last assessment,Neither dissatisfied nor satisfied | Last assessment, Somewhat satisfied | Last assessment, Very satisfied | Last assessment, Extremely satisfied | Last assessment, Missing |
|---|
| Disease Modifying Therapy (DS-DMT) | 16 | 13 | 39 | 61 | 46 | 31 | 17 | 205 | 29 | 37 | 52 | 74 | 89 | 97 | 40 | 10 | 19 | 38 | 42 | 53 | 73 | 91 | 30 | 82 | 9 | 11 | 13 | 24 | 46 | 67 | 26 | 232 | 4 | 6 | 12 | 15 | 29 | 58 | 29 | 275 | 3 | 4 | 4 | 8 | 22 | 60 | 26 | 301 | 46 | 61 | 57 | 58 | 69 | 94 | 37 | 6 |
,| Fingolimod | 10 | 22 | 29 | 62 | 35 | 42 | 14 | 219 | 8 | 14 | 8 | 32 | 52 | 161 | 154 | 4 | 5 | 11 | 11 | 46 | 43 | 153 | 144 | 20 | 8 | 15 | 11 | 25 | 57 | 130 | 151 | 36 | 7 | 8 | 12 | 21 | 42 | 135 | 145 | 63 | 7 | 7 | 11 | 27 | 34 | 115 | 150 | 82 | 14 | 15 | 23 | 45 | 43 | 128 | 162 | 3 |
Percent Change From Baseline in Brain Volume From Month 12 to Last Visit (Randomized)
Summary statistics for percent change from month 12 in brain volume by visit (Randomized treatment / randomized phase) in patients treated with fingolimod vs.DMTs as measured by MRI (NCT01623596)
Timeframe: 12 months, and Last assessment which is either at Month 12 or at early discontinuation
| Intervention | percent change in brain volume (Mean) |
|---|
| Percent change at 12 months (n=323, 111) | Percent change at Last assessment (n=370, 246) |
|---|
| Disease Modifying Therapy | -0.555 | -0.420 |
,| Fingolimod | -0.396 | -0.385 |
Primary and Secondary Reasons for Discontinuation From Randomized Treatment: Randomized Set
"Reasons for discontinuation in participants treated with fingolimod vs. DMT over 12 months of treatment~Total discontinued (Primary reason): Fingolimod arm: 27, MS-DMT arm: 27 = 54 participants~Total discontinued (Secondary reason): Fingolimod arm: 257, MS-DMT arm: 256 = 513 participants~Throughout the study, investigators evaluated each patient for occurrence of randomized treatment discontinuation and determined the primary and secondary reasons for such discontinuation. At every visit, the investigator evaluated the patients and determined if they should continue on randomized treatment or change to alternative treatment. Treatment discontinuation was a clinically meaningful measure related to safety, efficacy, and tolerability over time, reflecting the therapeutic effectiveness of study treatment." (NCT01623596)
Timeframe: at 12 months
| Intervention | participants (Number) |
|---|
| Occurrence of relapse (Primary reason) | Disease activity present in MRI (Primary reason) | Injection site reaction (Primary reason) | Flu-like symptoms (Primary reason) | Lipoatrophy (Primary reason) | Depression (Primary reason) | Hepatic side effects (Primary reason) | Spasticity (Primary reason) | Infection (Primary reason) | Macular edema (Primary reason) | Bradycardia (Primary reason) | Needle phobia (Primary reason) | Inconvenient administration (Primary reason) | Frequency of injections (Primary reason) | Neutralizing antibodies present (Primary reason) | Other (Primary reason) | Occurrence of relapse (Secondary reason) | Disease activity present in MRI (Secondary reason) | Injection site reaction (Secondary reason) | Flu-like symptoms (Secondary reason) | Lipoatrophy (Secondary reason) | Depression (Secondary reason) | Hepatic side effects (Secondary reason) | Spasticity (Secondary reason) | Infection (Secondary reason) | Macular edema (Secondary reason) | Bradycardia (Secondary reason) | Needle phobia (Secondary reason) | Inconvenient administration (Secondary reason) | Frequency of injections (Secondary reason) | Neutralizing antibodies present (Secondary reason) | Other (Secondary reason) |
|---|
| Disease Modifying Therapy (MS-DMT) | 14 | 6 | 61 | 34 | 1 | 4 | 3 | 1 | 0 | 0 | 0 | 13 | 33 | 29 | 0 | 58 | 3 | 5 | 40 | 16 | 1 | 6 | 0 | 2 | 0 | 0 | 0 | 18 | 55 | 45 | 0 | 65 |
,| Fingolimod | 5 | 0 | 0 | 0 | 0 | 1 | 7 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 13 | 0 | 2 | 0 | 1 | 0 | 0 | 5 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 17 |
RMSSD Normal Breathing
"Root Mean Square of the Successive Differences (RMSSD) is one of a few time-domain tools used to assess heart rate variability, the successive differences being neighboring RR or pulse intervals.~It is calculated as the square root of the mean of the squares of the successive differences between adjacent RR intervals or pulse intervals.~In this study pulse intervals were measured non-invasively during five minutes, while subjects were supine, breathing regularly.~Measurements were done at two timepoints t=0 and t=4,5hours. RMSSD was compared between these two timepoints." (NCT02048072)
Timeframe: t-4,5 hours
| Intervention | milliseconds (Mean) |
|---|
| Gilenya | 14.10 |
Participants Who Experienced at Least One Qualifying Cardiovascular Adverse Event
Participants from study CFTY720D2406 who experienced a qualifying cardiovascular adverse event were transferred to this study. Qualifying cardiovascular events included, but were not limited to, sudden unexplained death, cardiovascular death, myocardial infarction (MI), Q-wave MI, stroke (ischemic or hemorrhagic), unstable angina requiring hospitalization, congestive heart failure requiring hospitalization, complete heart block, ventricular fibrillation, torsade de pointes, hypertensive emergency and any other suspected life threatening cardiovascular condition. (NCT02232061)
Timeframe: Within 6 months of qualifying event up to 64 months
| Intervention | participants (Number) |
|---|
| Fingolimod | 0 |
Change From Baseline in T2 Lesion Volume
Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion volume (NCT01633112)
Timeframe: Baseline, 12 months/end of study
| Intervention | cubic centimeters (cc) (Mean) |
|---|
| FTY720 0.5 mg | -0.14 |
| FTY720 0.25 mg | -0.05 |
| GA 20 mg | 0.42 |
Confirmed Annualized Relapse Rate
Annualized relapse rate (ARR) was defined as the average number of confirmed relapses per year (i.e., the total number of confirmed relapses divided by the total days in the study multiplied by 365.25). The number of relapses included all the confirmed relapses experienced during the study from first dose to end of study. (NCT01633112)
Timeframe: up to 12 months
| Intervention | relapses/year (Number) |
|---|
| FTY720 0.5 mg | 0.153 |
| FTY720 0.25 mg | 0.221 |
| GA 20 mg | 0.258 |
Gd Enhancing T1 Lesion Count
Inflammatory activity based on MRI measurement of Gd enhancing T1 lesion count (NCT01633112)
Timeframe: At 12 months/end of study
| Intervention | lesions (Mean) |
|---|
| FTY720 0.5 mg | 0.4 |
| FTY720 0.25 mg | 0.4 |
| GA 20 mg | 0.9 |
New or Newly Enlarging T2 Lesions
Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion count. (NCT01633112)
Timeframe: At 12 months/end of study
| Intervention | Lesions (Mean) |
|---|
| FTY720 0.5 mg | 2.6 |
| FTY720 0.25 mg | 3.3 |
| GA 20 mg | 5.7 |
Number of Participants Free of New/Newly Enlarged T2 Lesions
Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion count. (NCT01633112)
Timeframe: At 12 months/end of study
| Intervention | Participants (Number) |
|---|
| FTY720 0.5 mg | 156 |
| FTY720 0.25 mg | 155 |
| GA 20 mg | 96 |
Percent Brain Volume Change From Baseline
Using a Central MRI vendor to ensure calibrated MRI scanning equipment across all sites, MRI scans were performed on subjects following the established parameters and transferred to the central vendor for review of quality and assessment/evaluation. (NCT01633112)
Timeframe: Baseline, 12 months, end of study
| Intervention | Percentages of volume change (Mean) |
|---|
| FTY720 0.5 mg | -0.652 |
| FTY720 0.25 mg | -0.636 |
| GA 20 mg | -0.561 |
Percentage of Patients Free of New T1 Hypointense Lesions
Based on MRI measures of new T1 hypointense lesions (NCT01633112)
Timeframe: 12 months
| Intervention | Percentage (Number) |
|---|
| FTY720 0.5 mg | 55.3 |
| FTY720 0.25 mg | 52.1 |
| GA 20 mg | 44.3 |
Change From Baseline in TSQM Scales
Treatment Satisfaction Questionnaire for Medication (TSQM) was developed and validated as a general measure for treatment satisfaction. Each scale score was calculated by summing individual items and then transformed to a 0-100 scale. Higher summary scores indicate better satisfaction with study drug. (NCT01633112)
Timeframe: 6 months, 12 months/end of study
| Intervention | score on a scale (Mean) |
|---|
| Global Satisfaction (Month 6) | Global Satisfaction (Month 12) | Effectiveness (Month 6) | Effectiveness (Month 12) | Side Effects (Month 6) | Side Effects (Month 12) | Convenience (Month 6) | Convenience (Month 12) |
|---|
| FTY720 0.25 mg | 23.4 | 20.5 | 18.2 | 17.9 | 18.8 | 17.2 | 26.5 | 26.5 |
,| FTY720 0.5 mg | 20.8 | 19.2 | 15.2 | 16.8 | 16.9 | 16.2 | 30.7 | 29.5 |
,| GA 20 mg | 14.4 | 9.4 | 12.9 | 8.0 | 9.3 | 7.6 | 4.4 | 0.8 |
Gd Enhancing T1 Lesion Volume
Inflammatory activity based on MRI measurement of Gd enhancing T1 lesion count (NCT01633112)
Timeframe: Baseline, 12 months/end of study
| Intervention | cubic centimeter (Mean) |
|---|
| Baseline | Month 12/end of study |
|---|
| FTY720 0.25 mg | 0.32 | 0.05 |
,| FTY720 0.5 mg | 0.31 | 0.06 |
,| GA 20 mg | 0.22 | 0.12 |