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

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.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Belimumab 1 mg/kg; Drug: Belimumab 10 mg/kg; Drug: Placebo

• Study Type: Observational
• Enrollment (Actual): 1016

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Adults with systemic lupus erythematosus (SLE); Subjects with SLE receiving ongoing stable SLE treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
SELENA SLEDAI	Percent of subjects with ≥ 4 point reduction from baseline in SELENA SLEDAI score at Week 52	Week 52
SF-36	Mean change in SF-36 Health Survey physical component summary score (PCS) at Week 24	Week 24
Time to first flare by SLE Flare Index	Time to 1st SLE flare after 24 weeks by modified SLE Flare Index	Up to Week 52

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Human Genome Sciences Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (ACTUAL): November 1, 2010
• Study Completion (ACTUAL): November 1, 2010

Study Registration Dates

• First Submitted: April 3, 2012
• First Submitted That Met QC Criteria: July 31, 2013
• First Posted (ESTIMATE): August 2, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): September 16, 2013
• Last Update Submitted That Met QC Criteria: September 12, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: quality of life; SLE; belimumab; BILAG; SELENA SLEDAI; flares; pooled analyses; steroid use; responder rate
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Belimumab
• Other Study ID Numbers: 114246