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

NCT01914770 | Completed

• 1 other identifier: 114246
• Study Type: observational
• Target: 1,016
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Systemic Lupus Erythematosus

Keywords

pooled analyses; quality of life; SELENA SLEDAI; SLE; steroid use; responder rate; flares; belimumab; BILAG

Outcome Measures

Primary Outcomes (1)

• Responder Rate

  Response is defined as: ≥4 point reduction from baseline in SELENA SLEDAI score, no worsening (increase of \< 0.30 points from baseline) in PGA, and no new BILAG A organ domain score or 2 new BILAG B organ domain scores.

  Week 52

Secondary Outcomes (3)

• SELENA SLEDAI

  Week 52

• SF-36

  Week 24

• Time to first flare by SLE Flare Index

  Up to Week 52

Study Arms (1)

Adults with systemic lupus erythematosus (SLE)

Subjects with SLE receiving ongoing stable SLE treatment

Drug: Belimumab 1 mg/kg; Drug: Belimumab 10 mg/kg; Drug: Placebo

Interventions

Belimumab 1 mg/kg DRUG

Subjects received belimumab 1 mg/kg in addition to their ongoing stable systemic lupus erythematosus (SLE) treatment regimen. Belimumab was administered intravenously at 0, 2, 4 weeks and every 4 weeks thereafter. The ongoing SLE treatment regimen was to have been stable 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 (ie, methotrexate, azathioprine, leflunomide, or mycophenolate calcineurin inhibitors, sirolimus, oral cyclophosphamide, 6-mercaptopurine, or thalidomide).

Adults with systemic lupus erythematosus (SLE)

Belimumab 10 mg/kg DRUG

Subjects received belimumab 10 mg/kg in addition to their ongoing stable SLE treatment regimen. Belimumab was administered intravenously at 0, 2, 4 weeks and every 4 weeks thereafter. The ongoing SLE treatment regimen was to have been stable 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, NSAIDs, or any immunosuppressive therapy (ie, methotrexate, azathioprine, leflunomide, or mycophenolate calcineurin inhibitors, sirolimus, oral cyclophosphamide, 6-mercaptopurine, or thalidomide).

Adults with systemic lupus erythematosus (SLE)

Placebo DRUG

Subjects received placebo in addition to their ongoing stable SLE treatment regimen. Placebo was administered intravenously at 0, 2, 4 weeks and every 4 weeks thereafter. The ongoing SLE treatment regimen was to have been stable 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, NSAIDs, or any immunosuppressive therapy (ie, methotrexate, azathioprine, leflunomide, or mycophenolate calcineurin inhibitors, sirolimus, oral cyclophosphamide, 6-mercaptopurine, or thalidomide).

Adults with systemic lupus erythematosus (SLE)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The primary population is the 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-double-stranded deoxyribonucleic acid (anti-dsDNA) positive (= 30 IU/mL) at baseline, OR * have low C3 and/or C4 complement relative to the normal range at baseline.

You may qualify if:

• 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).
• are anti-dsDNA positive (≥ 30 IU/mL) at baseline, OR
• have low C3 and/or C4 complement relative to the normal range at baseline.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Human Genome Sciences Inc.: collaborator

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

belimumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2012
• First Posted: August 2, 2013
• Study Start: July 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: September 16, 2013

Record last verified: 2013-09