Clinical Trials/NCT00430677

NCT00430677

Terminated

Phase 2

A Phase II/III Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo on a Background of Mycophenolate Mofetil and Glucocorticosteroids in Subjects With Active Proliferative Glomerulonephritis Due to Systemic Lupus Erythematosus (SLE)

Bristol-Myers Squibb15 sites in 2 countries423 target enrollmentJune 2007

ConditionsSystemic Lupus Erythematosus

InterventionsCorticosteroids (prednisone or prednisolone)Abatacept Mycophenolate mofetil (MMF)

DrugsCorticosteroids (prednisone or prednisolone)Abatacept Mycophenolate mofetil (MMF)

Overview

Phase: Phase 2
Intervention: Corticosteroids (prednisone or prednisolone)
Conditions: Systemic Lupus Erythematosus
Sponsor: Bristol-Myers Squibb
Enrollment: 423
Locations: 15
Primary Endpoint: Time to First Confirmed Complete Renal Response (CRR) During the Short-term (Double-blind) Period
Status: Terminated
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this clinical research study is to learn if addition of abatacept is safe and improves the effectiveness of treatment of patients with active lupus nephritis who are also taking mycophenolate mofetil (MMF) and corticosteroids.

Detailed Description

Double Blind Period: Treatment, Parallel Assignment, Double Blind (Subject, Investigator), Randomized, Active Control, Safety/Efficacy Study Open Label Period: Prevention, Single Group Assignment, Open Label, Uncontrolled, Safety/Efficacy Study

Registry

clinicaltrials.gov

Start Date

June 2007

End Date

August 2011

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Bristol-Myers Squibb

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Systemic Lupus Erythematosus (SLE) as defined by meeting at least 4 of the 11 classification criteria of the American College of Rheumatology for the classification of Systemic Lupus Erythematosus, either sequentially or coincident. The 4 criteria need not be present at study entry
•Renal biopsy within 12 months prior to screening visit indicating active proliferative lupus glomerulonephritis (met ISN/RPS Class III or IV classification criteria \[2003\], excluding Class III \[C\], IV-S \[C\] and IV-G \[C\], or the World Health Organization Class III or IV classification criteria \[1982\], excluding Class IIIc, IVd). If the renal biopsy was performed \>3 months but ≤12 months prior to screening visit, at least 1 of the following 3 serologies (performed locally) must have been abnormal prior to screening visit: complement (C3 or C4) level below normal range OR anti-dsDNA \>upper limit of normal range.
•A stable serum creatinine ≤3 mg/dL

Exclusion Criteria

•Subjects with a rise in serum creatinine of ≥1 mg/dL within 1 month prior to the screening visit
•Subjects with drug-induced SLE, as opposed to idiopathic SLE
•Subjects with severe, unstable and/or progressive Central nervous system (CNS) lupus
•Subjects with autoimmune disease other than SLE as their main diagnosis (e.g.; Rheumatoid arthritis (RA), Multiple Sclerosis \[MS\])
•Subjects who have received treatment with cyclophosphamide within 3 months of randomization (Day 1).
•Subjects who have received treatment with rituximab \< 6 months prior to the screening visit

Arms & Interventions

Abatacept 30 mg/kg+Corticosteroids+MMF

Short-term Period

Intervention: Corticosteroids (prednisone or prednisolone)

Abatacept 30 mg/kg+Corticosteroids+MMF

Short-term Period

Intervention: Abatacept

Placebo+Corticosteroids+MMF

Short-term Period

Intervention: Mycophenolate mofetil (MMF)

Abatacept 30 mg/kg+Corticosteroids+MMF

Short-term Period

Intervention: Mycophenolate mofetil (MMF)

Abatacept 10 mg/kg+Corticosteroids+MMF

Short-term Period

Intervention: Corticosteroids (prednisone or prednisolone)

Abatacept 10 mg/kg+Corticosteroids+MMF

Short-term Period

Intervention: Abatacept

Abatacept 10 mg/kg+Corticosteroids+MMF

Short-term Period

Intervention: Mycophenolate mofetil (MMF)

Placebo+Corticosteroids+MMF

Short-term Period

Intervention: Corticosteroids (prednisone or prednisolone)

Abatacept 10mg/kg

Long-term Extension Period

Intervention: Abatacept

Outcomes

Primary Outcomes

Time to First Confirmed Complete Renal Response (CRR) During the Short-term (Double-blind) Period

Time Frame: Day 1 (randomization) to 12 months.

Confirmed at 2 consecutive visits. CRR defined as meeting all of 5 criteria. Renal function (RF): (Glomerular filtration rate \[GFR\] calculated using Modification of Diet in Renal Diseases equation equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio \<30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.

Secondary Outcomes

Vital Signs Summary During the Short-term Period: Heart Rate(0 - 12 Months)
Vital Signs Summary During the Short-term Period: Temperature(0 - 12 Months)
Number of Participants With Death, Serious Adverse Events (SAE), Treatment-related Adverse Events SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs During Long-term Extension Period(From start of study drug in long-term period (Day 365) to up to 56 days after the last dose of the long-term extension (LTE). Deaths in LTE reported to >56 days post last dose.)
Change in SLICC/ACR Damage Index From Baseline During Short-term Period(Baseline (Day 1), Postbaseline (Month 12 or 28 days after last dose))
Baseline Physical Component Summary of the Short Form (SF)-36 During Short-term Period(Baseline (Day 1), Days 85, 169, 253, and 365)
Baseline Renal Function Over Time During Short-term Period(Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365)
Change From Baseline in Mental Component Summary of the SF-36 During Short-term Period(Baseline (Day 1), Days 85, 169, 253, and 365)
Baseline Fatigue as Measured by Fatigue Severity Scale-Krupp During Short-term Period(Baseline (Day 1), Days 85, 169, 253, and 365)
Number of Participants With Confirmed Complete Renal Response (CRR) During Short-term Period(Day 1 to 12 months)
Participants Achieving a Confirmed Complete Renal Response (CRR) at Month 12 During Short-term Period(At Month 12 from Day 1)
Time to Achieve First Confirmed Renal Improvement (RI) During Short-term Period (as Determined by Kaplan-Meier Methodology)(Day 1 (randomization) to 12 months.)
Change in Renal Function From Baseline Over Time During Short-term Period(Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365)
Baseline and Post Baseline Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index During Short-term Period(Baseline (Day 1), Post baseline (Month 12 or 28 days after last dose))
Number of Participants Achieving Renal Response (RR) at Month 12 During Short-term Period(Month 12)
Baseline Mental Component Summary of the Short SF-36 During Short-term Period(Baseline (Day 1), Days 85, 169, 253, and 365)
Baseline Fatigue as Measured by the Fatigue Visual Analog Scale During Short-term Period(Baseline (Day 1), Days 85, 169, 253, and 365)
Change in Fatigue From Baseline as Measured by the Fatigue Visual Analog Scale During Short-term Period(Baseline (Day 1), Days 85, 169, 253, and 365)
Participants Achieving Renal Improvement (RI) or CRR at Month 12 During Short-term Period(At Month 12 from Day 1)
Number of Months CRR Was Maintained During Short-term Period(Day 1 (randomization) to 12 Months)
Change From Baseline in Physical Component Summary of the SF-36 During Short-term Period(Baseline (Day 1), Days 85, 169, 253, and 365)
Number of Participants Achieving Complete Response by ACCESS Definition(End of short-term period (Day 365) to termination of the long-term extension period)
Change in Fatigue From Baseline as Measured by Fatigue Severity Scale-Krupp During Short-term Period(Baseline (Day 1), Days 85, 169, 253, and 365)
Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs Reported During the Short-term Period(From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.)
Participants With AEs of Special Interest During the Short-term Period(From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.)
Participants With Marked Hematology Abnormalities During the Short-term Period(From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.)
Participants With Marked Laboratory Abnormalities During the Short-term Period(From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.)
Participants With Marked Liver and Kidney Function Abnormalities During the Short-term Period(From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.)
Participants With Marked Abnormalities Urinalysis During the Short-term Period(From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.)
Vital Signs Summary During the Short-term Period: Systolic Blood Pressure (SBP)(0 - 12 Months)
Vital Signs Summary During the Short-term Period: Diastolic Blood Pressure (DBP)(0 - 12 Months)
Number of Participants With Positive Abatacept-induced Responses (ECL Method) Over Time During the Short-term Period(Day 169, Day 365)
Number of Participants Achieving Patient Response of Complete or Partial Response, Based on the June 2010 Food and Drug Administration Guidance Document for Lupus Nephritis(At Day 365 (end of Short-term Period) and Day 645)
Baseline Quantitative Immunoglobulins During the Short-term Period(Baseline (Day 1))
Change in Quantitative Immunoglobulin From Baseline During Short-term Period(Day 365)
Mean Change From Baseline in SLICC/ACR Damage Index(Day 365 to termination of the long-term extension phase)
Number of Participants With a Treatment-emergent Seropositive Result During the Long-term Extension Period(Day 365 to end of long-term extension period)
Number of Participants Achieving Renal Response(At Day 365 (end of short-term period) and Day 645)
Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period(From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period)
Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued)(From start of study drug on Day 365 to up to 56 days after last dose in the long-term extension period)