Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00430677
• Date of registration: 01/02/2007
• Prospective Registration: Yes
• Primary sponsor: Bristol-Myers Squibb
• Public title: Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis
• Scientific title: 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)
• Date of first enrolment: June 2007
• Target sample size: 423
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00430677
• Study type: Interventional
• Phase: Phase 2/Phase 3

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, China, France, Hong Kong, India, Japan, Korea, Republic of, Mexico, Philippines, Poland, Puerto Rico, Russian Federation, South Africa, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Bristol-Myers Squibb
• Affiliation: Bristol-Myers Squibb

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: Corticosteroids (prednisone or prednisolone)

Drug: Mycophenolate mofetil (MMF)

Drug: Abatacept

Primary Outcome(s)

Time to First Confirmed Complete Renal Response (CRR) During the Short-term (Double-blind) Period [Time Frame: Day 1 (randomization) to 12 months.]

Secondary Outcome(s)

Change in Fatigue From Baseline as Measured by Fatigue Severity Scale-Krupp During Short-term Period [Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365]

Number of Participants Achieving Renal Response (RR) at Month 12 During Short-term Period [Time Frame: Month 12]

Number of Participants With Confirmed Complete Renal Response (CRR) During Short-term Period [Time Frame: Day 1 to 12 months]

Participants Achieving Renal Improvement (RI) or CRR at Month 12 During Short-term Period [Time Frame: At Month 12 from Day 1]

Time to Achieve First Confirmed Renal Improvement (RI) During Short-term Period (as Determined by Kaplan-Meier Methodology) [Time Frame: Day 1 (randomization) to 12 months.]

Mean Change From Baseline in SLICC/ACR Damage Index [Time Frame: Day 365 to termination of the long-term extension phase]

Change in Renal Function From Baseline Over Time During Short-term Period [Time Frame: Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365]

Participants With Marked Laboratory Abnormalities During the Short-term Period [Time Frame: 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.]

Change in SLICC/ACR Damage Index From Baseline During Short-term Period [Time Frame: Baseline (Day 1), Postbaseline (Month 12 or 28 days after last dose)]

Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period [Time Frame: 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 Positive Abatacept-induced Responses (ECL Method) Over Time During the Short-term Period [Time Frame: Day 169, Day 365]

Participants Achieving a Confirmed Complete Renal Response (CRR) at Month 12 During Short-term Period [Time Frame: At Month 12 from Day 1]

Change in Fatigue From Baseline as Measured by the Fatigue Visual Analog Scale During Short-term Period [Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365]

Baseline Fatigue as Measured by Fatigue Severity Scale-Krupp During Short-term Period [Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365]

Change From Baseline in Mental Component Summary of the SF-36 During Short-term Period [Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365]

Baseline Renal Function Over Time During Short-term Period [Time Frame: 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 [Time Frame: Baseline (Day 1), Post baseline (Month 12 or 28 days after last dose)]

Change From Baseline in Physical Component Summary of the SF-36 During Short-term Period [Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365]

Baseline Fatigue as Measured by the Fatigue Visual Analog Scale During Short-term Period [Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365]

Baseline Mental Component Summary of the Short SF-36 During Short-term Period [Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365]

Change in Quantitative Immunoglobulin From Baseline During Short-term Period [Time Frame: Day 365]

Number of Participants Achieving Renal Response [Time Frame: At Day 365 (end of short-term period) and Day 645]

Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs Reported During the Short-term Period [Time Frame: 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 [Time Frame: 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.]

Baseline Physical Component Summary of the Short Form (SF)-36 During Short-term Period [Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365]

Participants With Marked Hematology Abnormalities During the Short-term Period [Time Frame: 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 [Time Frame: 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.]

Number of Participants Achieving Complete Response by ACCESS Definition [Time Frame: End of short-term period (Day 365) to termination of the long-term extension period]

Number of Participants With a Treatment-emergent Seropositive Result During the Long-term Extension Period [Time Frame: Day 365 to end of long-term extension period]

Participants With Marked Abnormalities Urinalysis During the Short-term Period [Time Frame: 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.]

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 [Time Frame: 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.]

Vital Signs Summary During the Short-term Period: Diastolic Blood Pressure (DBP) [Time Frame: 0 - 12 Months]

Vital Signs Summary During the Short-term Period: Temperature [Time Frame: 0 - 12 Months]

Baseline Quantitative Immunoglobulins During the Short-term Period [Time Frame: Baseline (Day 1)]

Number of Months CRR Was Maintained During Short-term Period [Time Frame: Day 1 (randomization) to 12 Months]

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 [Time Frame: At Day 365 (end of Short-term Period) and Day 645]

Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued) [Time Frame: From start of study drug on Day 365 to 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) [Time Frame: From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period]

Vital Signs Summary During the Short-term Period: Heart Rate [Time Frame: 0 - 12 Months]

Vital Signs Summary During the Short-term Period: Systolic Blood Pressure (SBP) [Time Frame: 0 - 12 Months]

Secondary ID(s)

IM101-075

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/05/2012
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00430677