Effectiveness of Belimumab Treatment in a Subpopulation of Systemic Lupus Erythematosus (SLE) Patients: a Pooled Analysis of BLISS-52 and BLISS-76

• Status: Completed
• Trial end date: 2010-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This pooled analysis will assess data from the Phase 3 belimumab registration studies BLISS-52 (aka BEL110752) and BLISS-76 (aka BEL110751). The analysis was pre-planned and agreed prior to the unblinding of either study. The primary objective is to evaluate the impact of belimumab treatment on a more severe subpopulation of systemic lupus erythematosus (SLE) subjects from BLISS-52 and BLISS-76 to aid physicians and payers in decision making. Subjects are from the modified Intent-to-Treat (ITT) population defined as randomized subjects who received at least 1 dose of study agent. This more severe subpopulation will have renal, neurological, haematological, or cardiovascular/respiratory organ domain involvement (as defined by a British Isles Lupus Assessment Group (BILAG) domain score of A, B or C in at least one of the domains) at baseline AND anti-double-stranded deoxyribonucleic acid (anti-dsDNA) positive (≥ 30 IU/mL) at baseline OR low C3 and/or C4 complement relative to the normal range at baseline.

• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Collaborator: Human Genome Sciences Inc.
• Treatments: 6-Mercaptopurine; Belimumab; Calcineurin Inhibitors

Criteria

Inclusion Criteria

• Eligible subjects for BLISS-52 and BLISS-76 included:

• clinical diagnosis of systemic lupus erythematosus (SLE) according to the American College of Rheumatology (ACR) criteria

• "active" (systemic lupus erythematosus) SLE disease, defined as a safety of oestrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) disease activity score of at least 6 at screening

• an unequivocally positive antinuclear antibodies (ANA) test result, from 2 independent time points within the study screening period or 1 positive historical test result and 1 positive test result during the screening period. ANA test results obtained in the screening period were only considered positive if the ANA titer ≥ 1:80 and/or anti-dsDNA serum antibody was ≥ 30 IU/mL

• on a stable SLE treatment regimen for at least 30 days prior to Day 0, which consisted of any of the following (alone or in combination): prednisone or equivalent (from 0 to 40 mg/day when used in combination with other SLE treatment or from 7.5 to 40 mg/day alone), anti-malarials, non-steroidal anti inflammatory drugs (NSAIDs), or any immunosuppressive therapy (i.e., methotrexate, azathioprine, leflunomide, or mycophenolate calcineurin inhibitors, sirolimus, oral cyclophosphamide, 6-mercaptopurine, or thalidomide).

• Additional inclusion criteria for the purpose of this analysis: subpopulation of patients from the pooled modified Intent-to-Treat population from BLISS-52 and BLISS-76 who have renal, neurological, haematological, or cardiovascular/respiratory organ domain involvement (as defined by a BILAG domain score of A, B or C in at least one of the domains) at baseline and 1 of the following:

• are anti-dsDNA positive (≥ 30 IU/mL) at baseline, OR

• have low C3 and/or C4 complement relative to the normal range at baseline.

Exclusion Criteria:

• Key exclusion criteria for BLISS-52 and BLISS-76 included:

• severe active lupus nephritis or Central Nervous System (CNS) lupus

• pregnancy

• receipt of any B cell target therapy at any time

• receipt of an investigational agent within 60 days prior to Day 0 for non-biologics and within 1 year for biologics

• receipt of abatacept (within 1 year), intravenous (IV) cyclophosphamide (within 6 months), anti-tumor necrosis factor (anti-TNF) therapy, anakinra, IV immunoglobulin (IVIG), prednisone > 100 mg/day, or plasmapheresis within 3 months, or live vaccine within 1 month.