Last updated: 07/21/2020 17:30:16
PGx7644: Meta-analysis of data from SLE patients treated with Benlysta in studies BEL112341, BEL110752/BLISS-52/C1056, and BEL110751/BLISS-76/C1057
Clinicaltrials.gov ID
Not applicable
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: PGx7644: Meta-analysis of data from SLE patients treated with Benlysta in studies BEL112341, BEL110752/BLISS-52/C1056, and BEL110751/BLISS-76/C1057
Trial 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).
Primary purpose:
Not applicable
Trial design:
Not applicable
Masking:
Not applicable
Allocation:
Not applicable
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:
Enrollment:
0
Primary completion date:
2016-23-03
Observational study model:
Cohort
Time perspective:
Retrospective
Clinical publications:
Pamela L. St. Jean, David A. Roth, Linda A. McCarthy, Arlene R. Hughes.PHARMACOGENETIC ANALYSIS OF BELIMUMAB FAILS TO IDENTIFY ROBUST GENETIC PREDICTORS OF EFFICACY IN LUPUS.Pharmacogenet Genomics.2019;29(6):132-135
DOI: 10.1097/FPC.0000000000000378
PMID: 31058715
Medical condition
Systemic Lupus Erythematosus
Product
belimumab
Collaborators
Not applicable
Study date(s)
September 2015 to March 2016
Type
Observational
Phase
Not applicable
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
none
- Provided written informed consent for PGx research when they enrolled in the clinical studies BEL110751, BEL110752 and BEL112341 and did not withdraw consent prior to PGx evaluation AND
- Were treated with belimumab 10 mg/kg IV or 200mg SC AND
- Did not provide written informed consent for PGx research when they enrolled in the clinical studies BEL110751, BEL110752 and BEL112341 or withdrew their PGx consent prior to genotyping being conducted OR
- Were not treated with o belimumab 10 mg/kg IV or 200mg SC OR
Inclusion and exclusion criteria
Inclusion criteria:
- Provided written informed consent for PGx research when they enrolled in the clinical studies BEL110751, BEL110752 and BEL112341 and did not withdraw consent prior to PGx evaluation AND
- Were treated with belimumab 10 mg/kg IV or 200mg SC AND
- Provided a blood sample for genotyping AND
- Successfully genotyped for at least one genetic marker under study AND
- Valid clinical data available
Exclusion criteria:
- Did not provide written informed consent for PGx research when they enrolled in the clinical studies BEL110751, BEL110752 and BEL112341 or withdrew their PGx consent prior to genotyping being conducted OR
- Were not treated with o belimumab 10 mg/kg IV or 200mg SC OR
- Did not provide any or an adequate blood sample for genotyping OR
- Failed genotyping OR
- Did not have valid clinical data available
Trial location(s)
This study does not involve prospective enrollment of participants.
Study documents
Statistical analysis plan
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
2016-23-03
Actual study completion date
2016-23-03
Plain language summaries
Not applicable. GSK’s transparency policy provides for Plain Language Summaries for Interventional studies.
Additional information about the trial
Not applicable
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