Clinical trial NCT01914770: Effectiveness of Belimumab Treatment in a Subpopulation of Systemic Lupus Erythematosus (SLE) Patients: a Pooled Analysis of BLISS-52 and BLISS-76
Official title: Effectiveness of Belimumab Treatment in a Subpopulation of Systemic Lupus Erythematosus (SLE) Patients: a Pooled Analysis of BLISS-52 and BLISS-76
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Systemic Lupus Erythematosus
Keywords: pooled analyses
quality of life
SELENA SLEDAI
SLE
steroid use
responder rate
flares
belimumab
BILAG
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Human Genome Sciences Inc.
First posted: 2013-08-02
Enrollment: 1016
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: RETROSPECTIVE
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.

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.


Eligibility 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.

Primary outcomes:
measure: Responder Rate
timeFrame: Week 52
Secondary outcomes:
measure: SELENA SLEDAI
timeFrame: Week 52
measure: SF-36
timeFrame: Week 24
measure: Time to first flare by SLE Flare Index
timeFrame: Up to Week 52
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: