azathioprine and Lupus Nephritis

azathioprine has been researched along with Lupus Nephritis in 231 studies

Azathioprine: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)
azathioprine : A thiopurine that is 6-mercaptopurine in which the mercapto hydrogen is replaced by a 1-methyl-4-nitroimidazol-5-yl group. It is a prodrug for mercaptopurine and is used as an immunosuppressant, prescribed for the treatment of inflammatory conditions and after organ transplantation and also for treatment of Crohn's didease and MS.

Lupus Nephritis: Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).

Research

Studies (231)

Authors

Clinical Trials (24)

Trial Overview

Trial Outcomes

Double-blind Period: Number of Participants With Time to Death or Renal Related Event

Events are defined as the first event experienced among the following: death, progression to end stage renal disease, doubling of serum creatinine from Baseline, renal worsening or renal-related treatment failure. Participants who discontinued randomized treatment, withdrew from the study, were lost to follow-up, or had a non renal-related treatment failure were censored. Participants who completed the 104-week treatment period were censored at the Week 104 visit. Time to event is defined as event date minus treatment start date plus one. Analysis was performed using Cox proportional hazards model for the comparison between Belimumab and Placebo adjusting for induction regimen, race, Baseline uPCR and Baseline eGFR. Number of participants with time to death or renal related event up to Week 104 has been presented. (NCT01639339)
Timeframe: Up to Week 104

Double-blind Period: Percentage of Participants With Complete Renal Response (CRR) at Week 104

CRR is defined as urinary protein creatinine ratio <0.5, eGRF was not more than 10% below the pre-flare value or >=90 mL/min/1.73m^2 and was not a treatment failure. Analysis was performed using a logistic regression model for the comparison between Belimumab and Placebo with covariates of induction regimen (CYC vs. MMF), race (Black vs. Non-Black), Baseline uPCR and Baseline eGFR. Percentage of participants with CRR at Week 104 has been presented. (NCT01639339)
Timeframe: Week 104

Double-blind Period: Percentage of Participants With PERR at Week 52

PERR is defined as urinary protein creatinine ratio <=0.7, eGRF was not more than 20% below the pre-flare value or >=60 mL/min/1.73m^2 and was not a treatment failure. Analysis was performed using a logistic regression model for the comparison between Belimumab and Placebo with covariates of induction regimen (CYC vs. MMF), race (Black vs. Non-Black), uPCR, and Baseline eGFR. Percentage of participants with PERR at Week 52 has been presented. (NCT01639339)
Timeframe: Week 52

Double-blind Period: Percentage of Participants With Primary Efficacy Renal Response (PERR) at Week 104

PERR is defined as urinary protein creatinine ratio <=0.7, estimated glomerular filtration rate (eGRF) was not more than 20 percent (%) below the pre-flare value or >=60 milliliters per minute per 1.73 square meter (mL/min/1.73m^2) and was not a treatment failure. Analysis was performed using a logistic regression model for the comparison between Belimumab and Placebo with covariates treatment group, induction regimen (CYC vs. MMF), race (Black vs. Non-Black), Baseline urine protein-creatinine ratio (uPCR), and Baseline eGFR. Modified Intent-to-treat (mITT) Population consisted of all randomized participants who received at least one dose of study treatment and were not excluded due to Good Clinical Practice (GCP) non-compliance. Percentage of participants with PERR at Week 104 has been presented. (NCT01639339)
Timeframe: Week 104

Double-blind Period: Number of Participants Reporting AESI

An AESI is one of scientific and medical concern specific to the product, for which ongoing monitoring and rapid communication by investigator to sponsor can be appropriate. A summary of protocol defined AESIs include malignant neoplasms including and excluding non-melanoma skin cancer (NMSC), post-infusion systemic reactions (PISR), all infections of special interest (opportunistic infections [OI], Herpes Zoster [HZ], tuberculosis [TB], and sepsis), depression (including mood disorders and anxiety)/suicide/self-injury and deaths. On-treatment data is displayed. (NCT01639339)
Timeframe: Up to Week 104

Double-blind Period: Number of Participants Reporting On-treatment AEs and SAEs

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with on-treatment AEs and SAEs has been reported. (NCT01639339)
Timeframe: Up to Week 104

Double-blind Period: Percentage of Participants With Ordinal Renal Response (ORR) at Week 104

ORR is defined with respect to reproducible responses that included CRR, partial RR (PRR) and non responder. CRR is reported when uPCR was <0.5, eGFR was not more than 10% below pre-flare GFR or within normal range and not a treatment failure. PRR is >=50% decrease from Baseline in uPCR and one of the following: value <1 if Baseline <=3, or value <3 if the Baseline was >3, eGFR not more than 10% below Baseline GFR or within normal range and not a treatment failure and not a CRR. Non responder is reported when neither CRR nor PRR criteria was met. Percentage of participants reporting CRR, PRR and non responders at Week 104 has been presented. (NCT01639339)
Timeframe: Week 104

Open-label Period: Number of Participants Reporting Adverse Events (AEs) and Serious AEs (SAEs)

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with AEs and SAEs have been reported. (NCT01639339)
Timeframe: From first open-label dose (Day 1) up to open-label Week 32 (8 weeks after last dose)

Open-label Period: Number of Participants Reporting Adverse Events of Special Interest (AESI)

An AESI is one of scientific and medical concern specific to the product, for which ongoing monitoring and rapid communication by investigator to sponsor can be appropriate. A summary of protocol defined AESIs include malignant neoplasms including and excluding non-melanoma skin cancer (NMSC), post-infusion systemic reactions (PISR), all infections of special interest (opportunistic infections [OI], Herpes Zoster [HZ], tuberculosis [TB], and sepsis), depression (including mood disorders and anxiety)/suicide/self-injury and deaths. (NCT01639339)
Timeframe: From first open-label dose (Day 1) up to open-label Week 32 (8 weeks after last dose)

Lupus Disease Activity - Negative Anti-dsDNA

"Lupus disease activity was assessed by 7 different measures: reduction in anti-dsDNA, negative anti-dsDNA, resolution of hypocomplementemia (C3, C4), frequency of flares, patient global assessment, SF36 total scores, and BILAG-2004 scores.~Participants with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. This measure was the number of participants who had negative anti-dsDNA at Week 104. Having a negative score is indicative of low lupus disease activity." (NCT00774852)
Timeframe: Week 104

Lupus Disease Activity - Participants Who Were Anti-dsDNA Positive at Baseline and Negative at Week 104

"Lupus disease activity was assessed by 7 different measures: reduction in anti-dsDNA, negative anti-dsDNA, resolution of hypocomplementemia (C3, C4), frequency of flares, patient global assessment, SF36 total scores, and BILAG-2004 scores.~Participants with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. One measure used to assess disease activity is the number of participants who were anti-dsDNA positive at baseline but negative at Week 104. Going from positive to negative is indicative of lowered lupus activity." (NCT00774852)
Timeframe: Week 104

Lupus Disease Activity - Patient Global Assessment

"Lupus disease activity was assessed by 7 different measures: anti-dsDNA, negative anti-dsDNA, resolution of hypocomplementemia (C3, C4), frequency of flares, patient global assessment (PGA), SF36 total scores, and BILAG-2004 scores.~PGA is measured on a 100mm scale and assessed at Weeks 0, 12, 24, 52, and 104. Higher values indicate greater burden of disease." (NCT00774852)
Timeframe: Week 104

Lupus Disease Activity - Patient Global Assessment Percent Change From Baseline

"Lupus disease activity was assessed by 7 different measures: anti-dsDNA, negative anti-dsDNA, resolution of hypocomplementemia (C3, C4), frequency of flares, patient global assessment (PGA), SF36 total scores, and BILAG-2004 scores.~PGA is measured on a 100mm scale and assessed at Weeks 0, 12, 24, 52, and 104. Higher values indicate greater burden of disease." (NCT00774852)
Timeframe: Week 104

Lupus Disease Activity - Total BILAG-2004

BILAG-2004 has 5 categories of scoring.Category A:defined by severe disease activity requiring any of the following treatments: 1) systemic high dose oral glucocorticoids, 2) IV pulse glucocorticoids, 3) systemic immunomodulators, or 4)therapeutic high dose anticoagulation in the presence of high dose steroids or immunomodulators. Category B:defined by moderate disease activity requiring any of the following treatments:1) systemic low dose oral glucocorticoids, 2) intramuscular or intra-articular or soft tissue glucocorticoids injection,3) topical glucocorticoids, 4) topical immunomodulators,5) antimalarials or thalidomide or prasterone or acitretin, or 6) symptomatic therapy.Category C:defined by mild disease.Category D is defined by inactive disease, previously affected.Category E is defined as the system never being involved.The categories are converted to a numeric score (A=9, B=3, C=1, D=0, E=0) and treated as a continuous variable. Higher score= more severe disease activity. (NCT00774852)
Timeframe: Week 52

Number of Participants Fulfilling the Proteinuria and Prednisone Criteria of a Complete Response

A complete proteinuria and prednisone response is defined as urine protein-to-creatinine ratio <0.5 and prednisone dose tapered to <= 10mg/day. Subjects who discontinued treatment or terminated from the study in the first 24 weeks are defined as response failures for all subsequent visits. Complete responders are those who successfully responded to treatment and have minimal activity of their lupus nephritis. (NCT00774852)
Timeframe: Week 24

Number of Participants Fulfilling the Proteinuria and Prednisone Criteria of a Partial Response

A partial proteinuria and prednisone response is defined as an improvement (reduction) of >=50% in the urine protein-to-creatinine ratio at either visit -1 or 0, and prednisone dose has been tapered to 10 mg/day. Subjects who discontinued treatment or terminated from the study in the first 24 weeks are defined as response failures for all subsequent visits. Partial responders are those who showed some response to treatment and low activity of their lupus nephritis. (NCT00774852)
Timeframe: Week 24

Number of Participants Who Achieved a Complete Response by Week 24 and Maintained the Complete Response Through Week 52

Complete response definition: a serum creatinine <= 1.2 mg/dL or <=125% of the higher value at either screening or baseline visit, protein-to-creatinine ratio <0.5, and prednisone dose tapered to <=10 mg/day or prednisone dosing allowances in protocol. Participants had to meet all of the referenced criteria to be considered a complete responder (CR). Participants who discontinued treatment and/or terminated from the study were defined as response failures for all subsequent visits. CRs are those who successfully responded to treatment and had minimal activity of their lupus nephritis. (NCT00774852)
Timeframe: Week 52

Number of Participants Who Achieved No Response at 24 Weeks and Continued in the Study

A participant who did not meet the criteria for either a complete response or a partial response at Week 24 was considered a non-responder. After Week 24, non-responders were terminated from the study and treated according to best clinical judgment unless the site investigator judged that the participant could benefit from continued participation. Non responders did not respond to treatment and lupus activity is moderate to severe. (NCT00774852)
Timeframe: Week 104

Number of Participants With a Complete or Partial Response

"Complete response: a serum creatinine <= 1.2 mg/dL or <=125% of the higher value at either screening or baseline visit, protein-to-creatinine ratio <0.5, and prednisone dose tapered to <=10 mg/day or prednisone dosing allowances in protocol. Participants had to meet all of the referenced criteria to be considered a complete responder.~Partial response: a serum creatinine <= 1.2 mg/dL or <= to 125% of the higher value at either screening or baseline visit, and improvement >= to 50% in the urine protein to creatinine ratio at either screening or baseline visit, and prednisone dose has been tapered to 10 mg/day or according to protocol dosing allowances in protocol.~Participants who discontinued treatment and/or terminated from the study were defined as response failures for all subsequent visits. CRs successfully responded to treatment and have minimal activity of their lupus nephritis. Partial responders showed some response to treatment and low activity of their lupus nephritis." (NCT00774852)
Timeframe: Week 52

Number of Participants With Complete Response

Complete response definition: a serum creatinine <= 1.2 mg/dL or <=125% of the higher value at either screening or baseline visit, protein-to-creatinine ratio <0.5, and prednisone dose tapered to <=10 mg/day or prednisone dosing allowances in protocol. Participants had to meet all of the referenced criteria to be considered a complete responder (CR). Participants who discontinued treatment and/or terminated from the study in the first 24 weeks were defined as CR failures for all subsequent visits. CRs are those who successfully responded to treatment and have minimal activity of their lupus nephritis. (NCT00774852)
Timeframe: Week 24

Number of Participants With Partial Response

Outcome measure description: Partial response definition: a serum creatinine <= 1.2 mg/dL or <= to 125% of the higher value at either screening or baseline visit, and improvement (reduction) >= to 50% in the urine protein to creatinine ratio at either screening or baseline visit, and prednisone dose has been tapered to 10 mg/day or according to protocol dosing allowances in protocol. Participants who discontinued treatment and/or terminated from the study in the first 24 weeks were defined as complete response failures for all subsequent visits. Partial responders are those who showed some response to treatment and low activity of their lupus nephritis. (NCT00774852)
Timeframe: Week 24

Lupus Disease Activity - Frequency of Flares

"Lupus disease activity was assessed by 7 different measures: anti-dsDNA, negative anti-dsDNA, resolution of hypocomplementemia (C3, C4), frequency of flares, patient global assessment, SF36 total scores, and BILAG-2004 scores.~Flares can be renal or non-renal. A renal flare is defined as two successive evaluations at least 1 week apart as proteinuria >1 gm/24h for participants who attain a complete response at Week 12 and for all other participants either 1) Increasing serum creatinine and persistent proteinuria, or 2) Worsening proteinuria. A non-renal flare is defined as any new post-baseline BILAG A in a non-renal organ system using BILAG-2004. This outcome measures the number of participants with the presence of renal and non-renal flares from Week 24 through Week 52 by response status. Having flares is indicative of more lupus disease activity." (NCT00774852)
Timeframe: Week 52

Lupus Disease Activity - Presence of Hypocomplementemia

"Lupus disease activity was assessed by 7 different measures: anti-dsDNA, negative anti-dsDNA, resolution of hypocomplementemia (C3, C4), frequency of flares, patient global assessment, SF36 total scores, and BILAG-2004 scores.~Participants were categorized as having hypocomplementemia if their serum complement test results (C3, and C4) were below the normal range at the site. Below normal complement test results are indicative of active lupus erythematosus." (NCT00774852)
Timeframe: Week 104

Lupus Disease Activity - SF-36 Scores

"Lupus disease activity was assessed by 7 different measures: anti-dsDNA, negative anti-dsDNA, resolution of hypocomplementemia (C3, C4), frequency of flares, patient global assessment, SF36 total scores, and BILAG-2004 scores.~The SF-36 is a quality of life assessment that was performed at Weeks 9, 24, 36, 52, and 104. Eight scale scores are derived from responses to the 36 items of the SF-36 questionnaire which were combined to produce the Physical Component Score and the Mental Component Score. The Physical Component Score is based on the Physical Functioning Scale (10 items), the Role-Physical Scale (4 items), the Bodily Pain Scale (2 items), and the General Health Scale (5 items). The Mental Component Score is based upon the Vitality Scale (4 items), the Social Functioning Scale (2 items), the Role-Emotional Scale (3 items) and the Mental Health Scale (5 items). Each component score is transformed into a 0-100 scale, with higher numbers indicating greater quality of life." (NCT00774852)
Timeframe: Week 104

Lupus Disease Activity - SF-36 Scores Percent Change From Baseline

"Lupus disease activity was assessed by 7 different measures: anti-dsDNA, negative anti-dsDNA, resolution of hypocomplementemia (C3, C4), frequency of flares, patient global assessment, SF36 total scores, and BILAG-2004 scores.~The SF-36 is a quality of life assessment that was performed at Weeks 9, 24, 36, 52, and 104. Eight scale scores are derived from responses to the 36 items of the SF-36 questionnaire which were combined to produce the Physical Component Score and the Mental Component Score. The Physical Component Score is based on the Physical Functioning Scale (10 items), the Role-Physical Scale (4 items), the Bodily Pain Scale (2 items), and the General Health Scale (5 items). The Mental Component Score is based upon the Vitality Scale (4 items), the Social Functioning Scale (2 items), the Role-Emotional Scale (3 items) and the Mental Health Scale (5 items). Each component score is transformed into a 0-100 scale, with higher numbers indicating greater quality of life." (NCT00774852)
Timeframe: Week 104

Proportion of Vaccinated Participants With a Competent Immune Response

"Among participants who are vaccinated, the number of who have a competent immune response at Week 52 as defined as having met both of the following criteria:~Pneumococcal vaccination response - absolute value >= 0.35 ug/mL and, when measured 4-6 weeks after vaccination, a >=2-fold increase from baseline in serotype-specific antibody titer for at least 50% of the serotypes tested.~Tetanus toxoid vaccination response - absolute value >=0.015 IU/mL and, when measured 4-6 weeks after vaccination, a 2-fold increase from baseline in antigen-specific antibody titer~Competent immune response is indicative of low disease activity." (NCT00774852)
Timeframe: Week 52

Duration of Renal Response (Number of Days)

Duration in days until second occurrence of UPCR >0.5 mg/mg in those subjects who achieve a reduction in UPCR to below 0.5 mg/mg (NCT03021499)
Timeframe: Week 52

Time to 50% Reduction in UPCR (Number of Days)

Time in days to reduction in Urine Protein Creatinine Ratio to decrease by 50% compared to baseline. Baseline is the average of two pre-randomisation values. (NCT03021499)
Timeframe: 52 weeks

Time to Urine Protein Creatinine Ratio of ≤0.5 mg/mg (Number of Days)

Time in days to reduction in Urine Protein Creatinine Ratio to decrease to 0.5 mg/mg or less. (NCT03021499)
Timeframe: 52 Weeks

Change From Baseline in eGFR

Change from baseline by visit in estimated Glomerular Filtration rate. eGFR is corrected to a maximum value of 90 mL/min/1.73 m2 (NCT03021499)
Timeframe: Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.

Change From Baseline in Patient Reported Outcomes

"Health-related quality of life (HRQoL) information was collected using the Short Form Health Survey (SF-36) HRQoL assessment and the LupusPRO (v1.7) assessment.~The SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. Scoring ranges from 0 to 100 with higher scores reflecting better health.~LupusPro assessment is a patient-reported questionnaire regarding the effect of lupus or its treatment on the patient's health, quality of life, and the medical care received related to lupus. The questionnaire consists of 43 questions within 8 HRQOL domains and 4 Non-HRQoL domains. Scores range from 0 to 100 with higher scores reflecting better quality of life." (NCT03021499)
Timeframe: Week 24 and Week 52

Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA - SLEDAI)

"Change from baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score at Week 24 and 52.~The SELENA-SLEDAI tool is a cumulative and weighted index used to assess disease activity across 24 different disease descriptors in patients with lupus. A patient's SELENA-SLEDAI total score is the sum of all marked lupus related descriptors (seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, cerebrovascular accident, vasculitis, arthritis, myositis, urinary casts, hematuria, proteinuria, pyuria, new rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement, increased DNA binding, fever, thrombocytopenia, leukopenia). A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity." (NCT03021499)
Timeframe: Week 24 and Week 52

Change From Baseline in UPCR

Change from baseline by visit in Urine Protein Creatinine Ratio. Baseline is the average of two pre-randomisation values. (NCT03021499)
Timeframe: Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.

Number of Participants With Adjudicated Renal Response at Week 52

"The primary efficacy endpoint was the number of subjects showing renal response at Week 52. Renal response was adjudicated based on blinded data by an independent Clinical Endpoints Committee based on meeting the following criteria~UPCR of ≤0.5 mg/mg &~eGFR ≥60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of >20% &~Received no rescue medication for LN &~Did not receive more than 10 mg prednisone for ≥3 consecutive days or for ≥7 days in total during Weeks 44 through 52, prior to assessment Note:To be disqualified from renal response, the subject had to fail both eGFR measures (i.e., confirmed eGFR <60 mL/min/1.73 m2 & confirmed >20% drop from baseline) & have an associated treatment-related or disease-related AE that impacted eGFR Withdrawals prior to Week 52 with insufficient Week 52 data to determine response were defined non responders. Subjects who discontinued study drug but continued to attend study visits had their data assessed for response" (NCT03021499)
Timeframe: 52 Weeks

Number of Participants With Reduction in Urine Protein Creatinine Ratio to 0.5 mg/mg or Less

Number of Participants With Reduction in Urine Protein Creatinine Ratio to 0.5 mg/mg or Less (NCT03021499)
Timeframe: 52 Weeks

Number of Participants With Renal Response at Week 24

"Number of subjects showing renal response at Week 24. Renal response was adjudicated based on blinded data by an Independent Clinical Endpoints Committee based on the following criteria:~UPCR of ≤0.5 mg/mg, & eGFR ≥60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of >20%, and Received no rescue medication for LN & Did not receive more than 10 mg prednisone for ≥3 consecutive days or for ≥7 days in total during Weeks 16 through 24, just prior to the renal response assessment. Note:To be disqualified from renal response, the subject had to fail both eGFR measures (i.e., confirmed eGFR <60 mL/min/1.73 m2 AND confirmed >20% drop from BL) & have an associated treatment-related or disease-related AE that impacted eGFR. Subjects who withdrew prior to the Week 24 assessment and provided insufficient Week 24 data to determine response were defined as non-responders. Subjects who discontinued study drug but continued to attend study visits had their data assessed for response." (NCT03021499)
Timeframe: Week 24

Number of Subjects Achieving 50% Reduction in Urine Protein Creatinine Ratio

Number of subjects achieving 50% reduction in Urine Protein Creatinine ratio (NCT03021499)
Timeframe: 52 Weeks

Number of Subjects Achieving, and Remaining in, Renal Response (Urine Protein Creatinine Ratio ≤0.5 mg/mg)

Number of subjects achieving, and remaining in, renal response (Urine Protein Creatinine ratio ≤0.5 mg/mg) (NCT03021499)
Timeframe: Week 52

Number of Subjects With Partial Renal Response at Weeks 24 & 52

Number of subjects with partial Renal Response (defined as a 50% reduction in UPCR from baseline) at Week 24 and at Week 52. Baseline UPCR is the average of 2 pre-randomisation values. (NCT03021499)
Timeframe: Weeks 24 and 52

Number of Subjects With Renal Response With Low Dose Steroids

Programmed Renal Response whilst on low dose steroids (<2.5 mg/day) for the preceding 8 Weeks at Weeks 24 and 52 (NCT03021499)
Timeframe: Week 24 and Week 52

Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Deaths

Treatment Failure was adjudicated by a clinical endpoints committee (CEC) and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis (LN). (NCT00377637)
Timeframe: From the start of the Maintenance Phase to Month 36

Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With End-stage Renal Disease (ESRD)

Time to treatment failure, adjudicated by the Clinical Endpoints Committee (CEC), was defined as any 1 the following: death, ESRD, sustained doubling of serum creatinine, renal flare (proteinuric or nephritic), or requirement for rescue therapy to treat deterioration or exacerbation of Lupus nephritis. ESRD is defined as progression to chronic hemodialysis or renal transplant. (NCT00377637)
Timeframe: From the start of the Maintenance Phase to Month 36

Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With Sustained Doubling of Serum Creatinine

Sustained doubling of serum creatinine concentration is defined as the first serum creatinine value that is twice the mean of the lowest 2 values from screening to end of induction, as confirmed by a second serum creatinine value obtained at least 4 weeks after the initial doubling. (NCT00377637)
Timeframe: From the start of the Maintenance Phase to Month 36

Maintenance Phase: Participants With Major Extra-renal Flare

A major extra-renal flare is defined as a British Isles Lupus Assessment Group (BILAG) Score category A in one extrarenal organ or three organs with concurrent category B scores. BILAG indices provide a scoring system for the assessment of lupus disease activity in terms of the need for steroid treatment in 8 organs/systems. Eighty-six items were scored resulting in a classification of A (severe activity), B (moderate activity), C (mild activity), D (no current activity) and E (no activity ever observed) for each organ system. (NCT00377637)
Timeframe: From the start of the Maintenance Phase to Month 36

Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores

The SF-36 is a 36 item quality of life questionnaire. The short-form version has eleven questions that permit the participant to rate how they feel that particular day. The SF-36 consists of eight scaled scores and two component scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 score with the higher scores indicating better quality of life. (NCT00377637)
Timeframe: Baseline and 24 weeks

Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein

24-hour urine protein was measured at Baseline and Week 24. (NCT00377637)
Timeframe: Baseline, Week 24

Induction Phase: Change From Baseline to Week 24 in Serum Albumin

(NCT00377637)
Timeframe: Baseline, Week 24

Induction Phase: Change From Baseline to Week 24 in Serum Creatinine

(NCT00377637)
Timeframe: Baseline, Week 24

Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score

"BILAG indices provide a scoring system for the assessment of lupus disease activity in terms of the need for steroid treatment in 8 organs/systems. Eighty-six items were scored resulting in a classification of A (severe activity), B (moderate activity), C (mild activity), D (no current activity) and E (no activity ever observed) for each organ system. The BILAG individual system summaries were calculated by a program supplied by ADS-Limathon (Sheffield, UK).~The score at baseline was compared to the score at the 24 week endpoint for each treatment group, reported here for the renal system." (NCT00377637)
Timeframe: Baseline, 24 weeks

Induction Phase: Number of Participants Achieving Complete Remission

Number of participants achieving complete remission as defined by return to normal serum creatinine, proteinuria ≤500 mg/24 hours and an inactive urinary sediment (absence of red blood cells, white blood cells or cellular or granular casts) after 24 weeks. (NCT00377637)
Timeframe: 24 weeks

Induction Phase: Number of Patients Showing Treatment Response

Treatment response was adjudicated by a blinded clinical endpoints committee (CEC) and defined as: a) Decrease in proteinuria, defined as a decrease in the urine protein to creatinine ratio (UPCr) to <3 in subjects with baseline proteinuria ≥3 UPCr or a decrease in the UPCr by ≥50% in subjects with proteinuria <3 UPCr at Baseline, and b) Stabilization of serum creatinine or improvement. UPCr were derived from the 24 hour urine collection. Patients who did not show a treatment response at Week 24 or who withdrew earlier than Week 24 were considered non-responders. (NCT00377637)
Timeframe: 24 weeks

Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy

The primary efficacy parameter was the time to treatment failure, adjudicated by the Clinical Endpoints Committee (CEC), defined as any of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or requirement for rescue therapy to treat deterioration or exacerbation of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to rescue treatment for each patient. The data presented are the percentage of participants who were rescue treatment free at each time interval as estimated by Kaplan-Meier. (NCT00377637)
Timeframe: From the start of the Maintenance Phase to Month 36

Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval

A proteinuric flare is defined as a doubling of the urine protein:creatinine ratio, and proteinuria ≥1 g/24 h in patients with urine protein ≤0.5 g/24 h at the end of the induction phase, or proteinuria ≥2 g/24 h if urine protein was >0.5 g/24 h at the end of the induction phase. A nephritic flare is defined as a 25% increase in serum creatinine accompanied by 1 or more of the following: (a) simultaneous doubling of the proteinuria reaching a minimum of 2 g/24 h (b) new/increased hematuria or (c) the appearance of cellular casts. All flares were adjudicated by a clinical endpoints committee. (NCT00377637)
Timeframe: From the start of the Maintenance Phase to Month 36

Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval

Treatment Failure was adjudicated by a clinical endpoints committee and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to treatment failure for each patient. The data presented are the percentage of participants who were treatment-failure free at each time interval as estimated by Kaplan-Meier. (NCT00377637)
Timeframe: From the start of the Maintenance Phase to Month 36

Adverse Events (AE) Profile and Routine Biochemical and Hematological Assessments.

"Number (and percent) of adverse events experienced during the AURORA 2 treatment period.~To assess the long-term safety and tolerability of voclosporin compared with placebo for up to an additional 24 months following completion of treatment in the AURORA 1 study in subjects with LN." (NCT03597464)
Timeframe: Month 12 (AURORA 2 baseline) to Month 36

Change From AURORA 1 Baseline (i.e., Month 0) in Estimated Glomerular Filtration Rate (eGFR)

"Participants analyzed included all subjects who were randomized treatment during AURORA 1 AND who consented to continue their treatment in AURORA 2. Baseline values were collected at the start of AURORA 1 but only for those subjects that continued in AURORA 2.~This endpoint incorporated Corrected eGFR values with a ceiling set to 90 mL/min/1.73 m^2~Increases in eGFR levels are indicative of better renal outcomes." (NCT03597464)
Timeframe: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36

Change From AURORA 1 Baseline (i.e., Month 0) in Safety of Estrogens in Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)

"Participants analyzed included all subjects who were randomized treatment during AURORA 1 AND who consented to continue their treatment in AURORA 2. Baseline values were collected at the start of AURORA 1 but only for those subjects that continued in AURORA 2.~Assessment of Systemic Lupus Erythematosus (SLE) Disease Activity within the last 10 days. It scores 24 disease descriptors across 9 organ systems which are summed to a minimum of <2 (considered indicative of no activity) and maximum of 105 points. Scores are weighted and a score of 6 is considered clinically significant. Higher scores indicate worse disease activity." (NCT03597464)
Timeframe: Months 18, 24 and 36

Change From AURORA 1 Baseline (i.e., Month 0) in Serum Creatinine (SCr)

"Participants analyzed included all subjects who were randomized treatment during AURORA 1 AND who consented to continue their treatment in AURORA 2. Baseline values were collected at the start of AURORA 1 but only for those subjects that continued in AURORA 2.~Decreases in SCr levels can be indicative of better renal outcomes." (NCT03597464)
Timeframe: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36

Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein

"Participants analyzed included all subjects who were randomized treatment during AURORA 1 AND who consented to continue their treatment in AURORA 2. Baseline values were collected at the start of AURORA 1 but only for those subjects that continued in AURORA 2.~Reductions in Urine Protein levels are indicative of better renal outcomes." (NCT03597464)
Timeframe: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36

Change From AURORA 1 Baseline (i.e., Month 0) in Urine Protein to Creatinine Ratio (UPCR)

"Participants analyzed included all subjects who were randomized treatment during AURORA 1 AND who consented to continue their treatment in AURORA 2. Baseline values were collected at the start of AURORA 1 but only for those subjects that continued in AURORA 2.~Reductions in UPCR are indicative of better renal outcomes." (NCT03597464)
Timeframe: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36

Number (and Percent) of Subjects in Partial Renal Response

Partial renal response defined as a 50% reduction from baseline in urine protein creatinine ratio (UPCR). (NCT03597464)
Timeframe: Months 12 (AURORA 2 baseline), 18, 24, 30 and 36

Number (and Percent) of Subjects in Renal Response

"Proportion of subjects in renal response defined as:~urine protein creatinine ratio (UPCR) of ≤0.5 mg/mg~estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m^2 or no confirmed decrease from baseline in eGFR of >20%~Received no rescue medication for LN~Did not receive more than 10 mg prednisone for ≥3 consecutive days or for ≥7 days in total during the 8 weeks prior to the renal response assessment." (NCT03597464)
Timeframe: Months 12 (AURORA 2 Baseline), 18, 24, 30 and 36

Duration of Complete Remission (Number of Weeks)

Duration of Complete Remission is defined as time of first occurrence of UPCR ≤ 0.5 mg/mg until the second increase above 0.5 mg/mg (i.e. a single occurrence above 0.5 is permitted) or use of rescue medication. (NCT02141672)
Timeframe: week 48

Number of Subjects Achieving Partial Remission

Partial remission is defined as a 50% reduction in UPCR from baseline at Week 24 and Week 48. (NCT02141672)
Timeframe: week 48

Number of Subjects Achieving Sustained Early Complete Remission

Sustained early complete remission defined as complete remission that occurred on or before Week 24 and was sustained through Week 48 (NCT02141672)
Timeframe: week 48

Number of Subjects Achieving Sustained Early Partial Remission

Early partial remission defined as partial remission that occurred on or before Week 24 and was sustained through Week 48 (NCT02141672)
Timeframe: week 48

Number of Subjects Achieving Sustained Partial Remission

Sustained partial remission defined as the first occurrence of partial remission that was sustained through Week 48 (NCT02141672)
Timeframe: week 48

Time to Complete Remission (Number of Weeks)

Time to Complete Remission is defined as time from first dose of voclosporin/placebo to UPCR ≤ 0.5mg in the absence of rescue medication. (NCT02141672)
Timeframe: week 48

Time to Partial Remission (Number of Weeks)

Time to partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction sustained until week 48 in the absence of rescue medication. (NCT02141672)
Timeframe: week 48

Time to Sustained Early Complete Remission (Number of Weeks)

Time to Sustained Complete Remission is defined as time from first dose of voclosporin/placebo to UPCR ≤ 0.5mg occurring at week 24 or earlier and sustained until week 48 in the absence of rescue medication. (NCT02141672)
Timeframe: week 48

Time to Sustained Early Partial Remission (Number of Weeks)

Time to sustained early partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction occurring at week 24 or earlier and sustained until week 48 in the absence of rescue medication. (NCT02141672)
Timeframe: week 48

Time to Sustained Partial Remission (Number of Weeks)

Time to sustained partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction sustained until week 48 in the absence of rescue medication. (NCT02141672)
Timeframe: week 48

Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score

"The SELENA-SLEDAI assesses disease activity within the last 10 days. Twenty-four items are scored for nine organ systems, and summed to a maximum of 105 points. A score of 6 is considered clinically significant and indicates active disease. For analysis purposes, a score ≥6 was categorized as high. The 24 items are as follows: seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, cerebrovascular accident, vasculitis, arthritis, myositis, urinary casts, hematuria, proteinuria, pyuria, new rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement, increased DNA binding, fever, thrombocytopenia, and leukopenia." (NCT02141672)
Timeframe: Baseline, Week 24 and Week 48

Change From Baseline in UPCR at Weeks 24 and 48

Change from baseline in urine protein creatinine ratio at weeks 24 and 48 (NCT02141672)
Timeframe: Baseline, Week 24 and Week 48

Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids

"Complete remission is defined as:~Confirmed protein/creatinine ratio of ≤0.5 mg/mg and~eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or >10 mg prednisone for >3 consecutive days or >7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission.~Low-dose steroids is defined as use of ≤5 mg prednisone for 8 weeks leading up to the Week 24 visit date or for 12 weeks leading up to the Week 48 visit date." (NCT02141672)
Timeframe: Weeks 24 and 48

Number of Subjects Achieving Complete Renal Remission at 24 Weeks

"Complete remission is defined as:~Confirmed protein/creatinine ratio of ≤0.5 mg/mg and~eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or >10 mg prednisone for >3 consecutive days or >7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission." (NCT02141672)
Timeframe: week 24

Number of Subjects Achieving Complete Renal Remission at 48 Weeks

"Complete remission is defined as:~Confirmed protein/creatinine ratio of ≤0.5 mg/mg and~eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or >10 mg prednisone for >3 consecutive days or >7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission." (NCT02141672)
Timeframe: Week 48

Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks

Number of patients with partial Remission is defined as time from first dose of voclosporin/placebo to 50% UPCR reduction at week 24 or week 48 in the absence of rescue medication. (NCT02141672)
Timeframe: week 24 and 48

Number of Subjects Achieving, and Remaining in, Complete Remission

Sustained complete remission defined as the first occurrence of complete remission that was sustained through Week 48 (NCT02141672)
Timeframe: week 48

Number of Adverse Events (AEs)Grade 3 or Higher Experienced by Participant During Treatment Phase of Study

"Number of adverse events (AEs) or serious adverse events (SAEs) Grade 3 or higher experienced by participant over the duration of the treatment period. [1]~[1] This study graded the severity of AEs experienced by the study participant according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0." (NCT00447265)
Timeframe: 24 Weeks

Number of Participant Adverse Events (AEs) From Baseline to Early Study Withdrawal Visit

Number of participant AEs during the trial. This study graded the severity of AEs experienced by the study participant according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0. (NCT00447265)
Timeframe: 39 Weeks

Number of Participants With a B to D Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Musculoskeletal Score

Reported here is the number of participants with a change in their BILAG Musculoskeletal Score from B (at baseline) to D (at week 24). A single alphabetic score (A through E) is used to denote disease severity. The BILAG score is a converted numerical score (A=9, B=3, C=1, D=0, E=0).A maximum musculoskeletal score of 9 signifies higher disease activity and a score of 0 is indicative of inactive systematic lupus erythematosus (SLE) in the specified organ system. (NCT00447265)
Timeframe: Baseline, Week 24

Number of Participants With a C to B Score Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Mucocutaneous Score

Reported here is the number of participants with a change in their BILAG Mucocutaneous Score from C (at baseline) to B (at week 24). A single alphabetic score (A through E) is used to denote disease severity. The BILAG score is a converted numerical score (A=9, B=3, C=1, D=0, E=0). A maximum mucocutaneous score of 9 signifies higher disease activity and a score of 0 is indicative of inactive systematic lupus erythematosus (SLE) in the specified organ system. (NCT00447265)
Timeframe: Baseline, Week 24

Number of Participants With an A to B Score Change From Baseline to Week 24 in the British Isles Lupus Assessment Group (BILAG) Renal Score

Reported here is the number of participants with a change in their BILAG Renal Score from A (at baseline) to B (at week 24). A single alphabetic score (A through E) is used to denote disease severity. The BILAG score is a converted numerical score (A=9, B=3, C=1, D=0, E=0).A maximum renal score of 9 signifies higher disease activity and a score of 0 is indicative of inactive systematic lupus erythematosus (SLE) in the specified organ system (NCT00447265)
Timeframe: Baseline, Week 24

Percent of Participants Who Achieved a Renal Response at Week 24

"Percent of study participants who achieved a renal response at 24 weeks.[1]~[1]A renal response is defined as: 1) 50% reduction in proteinuria compared to baseline as measured by urinary protein: creatinine ratio; and 2) stable or improving renal function as defined by the Glomerular filtration rate (GFR) calculated based on the Modification of Diet in Renal Disease equation (Levy, AS, Coresh J, Galk E et al, National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med, 139(2): 137-47, 2003)" (NCT00447265)
Timeframe: Week 24

Time to Participant's Renal Response

"Time to when participant achieved a renal response[1]~[1]A renal response is defined as: 1) 50% reduction in proteinuria compared to baseline as measured by urinary protein: creatinine ratio; and 2) stable or improving renal function as defined by the Glomerular filtration rate (GFR) calculated based on the Modification of Diet in Renal Disease equation (Levy, AS, Coresh J, Galk E et al, National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med, 139(2): 137-47, 2003)" (NCT00447265)
Timeframe: First 24 Weeks of Study Period

Participant Medical Outcome Study Short Form 36 (SF-36) Mental Component Score at Baseline and Week 24

"Reported here are the participant SF-36 Mental Component scores at baseline and week 24. The SF-36 measures 8 domains: physical functioning, role limitations due to physical health, bodily pain, social functioning, mental health, role limitations due to emotional problems, vitality, and general health perceptions.[1] The Mental Component score of the SF-36 ranges from 0 to 100; 0 equals worst health state. Higher numbers reported here indicate more improvement in condition from baseline.~[1]Ref: Ware JE, Sherbourne CD. The MOS36-item short-form health survey. Med Care. 1992; 30:473-483" (NCT00447265)
Timeframe: Baseline, Week 24

Participant Medical Outcome Study Short-Form 36 (SF-36) Physical Component Score at Baseline and Week 24

"Reported here is the participant baseline and week 24 SF-36 Physical Component scores. The SF-36 measures 8 domains: physical functioning, role limitations due to physical health, body pain, social functioning, mental health, role limitations due to emotional problems, vitality, and general health perceptions[1]. The Physical Component scores of the SF-36 range from 0 to 100; 0 equals worst health state. Higher numbers reported here indicate more improvement in condition from baseline.~[1]Ref: Ware JE, Sherbourne CD. The MOS36-item short-form health survey Med Care. 1992; 30:473-483." (NCT00447265)
Timeframe: Baseline, Week 24

Participant Systematic Lupus Erythematosus Disease Activity Index (SLEDAI) Score at Baseline and at Early Study Withdrawal Visit

Reported here is the baseline and week 39 Systematic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. The SLEDAI is a concise measure of lupus disease activity with excellent test-retest reliability and high responsiveness to clinically important changes in the disease. The total score is derived from ratings on 24 conditions plus the Physician's Global Assessment; 0 indicates inactive disease and the maximum theoretical score is 105, with higher scores representing increased disease activity. (NCT00447265)
Timeframe: Baseline, Week 39 (Early Study Withdrawal Visit)

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