Completed

Study Description:

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by autoantibody production and abnormal B lymphocyte function. The etiology of SLE is unknown, although genetics, sex hormones, and environmental conditions are thought to play a role. This disease is more common in women (~90 percent of patients) than men and more prevalent in African-Americans than Caucasians. Belimumab (also known as LymphoStat-B™; BENLYSTA®) is a B-lymphocyte stimulator (BLyS)-specific inhibitor that blocks the binding of soluble BLyS, a B-cell survival factor, to its receptors on B cells. Belimumab does not bind B cells directly, but by binding BLyS, belimumab inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells. Phase 3 studies of intravenous (IV)-administered belimumab in SLE (BEL110752/BLISS-52/C1056 and BEL11751/BLISS-76/C1057) were completed in 2009 and 2010 and formed the basis of the approval of IV belimumab in the United States (US), Canada and the European Union (EU). Pharmacogenetic evaluations were performed on these two phase III studies that evaluated genetic variants across the genome for an association with belimumab efficacy. None of the genetic variants tested met pre-defined thresholds for statistical significance in accounting for variation in efficacy response to 10milligrams (mg)/kilogram (kg) belimumab at 52 weeks in either study separately or when meta-analyzed together. A phase III study of 200mg subcutaneously-administered belimumab (BEL112341) was completed in 2015 and showed a significant response to treatment as defined by a reduction in disease activity as defined by the SLE-responder index (SRI4). A pharmacogenetic evaluation was performed on this study (PGx7643, study 204927), concluding that none of the genetic variants tested met pre-defined thresholds for significance in accounting for variability in Benlysta efficacy. The current evaluation combines data on genetic variation across the genome for an association with efficacy in SLE subjects treated with belimumab in the three phase III clinical studies (BEL112341, BEL110752, BEL110751).

GSK Study ID:

204901


Has Results Document Available
ClinicalTrials.gov Identifier:

Not Available


EudraCT Number:

Not Available


Study Overview

Medical Conditions

Lupus

Product

belimumab

Collaborators

N/A


Date

September 2015 to March 2016

Type

Observational

Phase

N/A


Gender

Both

Age

18 Year+

Accepts Healthy Volunteers

none


Locations


Study Design

  • Primary Purpose: Not Available
  • Allocation: Not Available
  • Study Design: Not Available
  • Study Classification: Not Available
  • Masking: Not Available
  • Masked Subject: Not Available
  • Masked Caregiver: Not Available
  • Masked Investigator: Not Available
  • Masked Assessor: Not Available
Primary Outcomes:

  • Belimumab efficacy as defined by SRI48 response in subjects at week 52
    Timeframe: Week 52

Secondary Outcomes:

  • Belimumab efficacy as defined by SRI4 response at week 52 and in the subset of these subjects with high disease at baseline
    Timeframe: Week 52

Interventions:

  • other: Belimumab 10 mg/kg IV
  • other: Belimumab 200 mg SC

Keyword:

  • PGx7643, genome-wide association study, Systemic Lupus Erythematosus, PGx, Benlysta, GSK1550188, BEL112341, BLISS-52, GWAS, pharmacogenetics, subcutaneous, efficacy, SLE, BEL110751, BLISS-76, 204901, belimumab, BEL110752
Inclusion / Exclusion Criteria: Click to view inclusion/exclusion criteria:
Enrollment: