A Pooled Analysis of the HGS1006-C1056 (BLISS-52) and HGS1006-C1057 (BLISS-76) Studies

NCT ID: NCT01858792

Last Updated: 2013-05-21

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2011-06-30

Brief Summary

Efficacy and Safety of Belimumab in a Subgroup of Systemic Lupus Erythematosus (SLE) Patients with Higher Disease Activity (anti-dsDNA positive and low complement): A Pooled Analysis of the HGS1006-C1056 (BLISS-52) and HGS1006-C1057 (BLISS-76) Studies

Detailed Description

Studies C1056 and C1057 followed very similar protocols, were of nearly identical design, had common inclusion and exclusion criteria, and were conducted over the same time period. Nevertheless, given the heterogeneous presentation of SLE disease and the fact that the Phase III program was run globally, variation in the patient population, both within the studies (e.g., between different centres) and between the studies (analogous to differences between centres within the same study) should be expected.

Since it has been established that the conduct of the studies was effectively the same, it then must be determined whether the relative treatment effect is different in one study compared with the other study when evaluating whether two studies are similar enough to pool. Each of these Phase III studies achieved statistical significance for belimumab 10 mg/kg on the pre-specified primary endpoint of SRI response at Week 52; therefore, these nearly identical studies provide independent replication of results. While pooling is not necessary to establish the effectiveness of belimumab, it was considered appropriate in order to evaluate treatment effects in the high disease activity subgroup of interest, given that the individual studies were not designed to provide sufficient power to demonstrate effectiveness within subgroups. Thus, statistical evaluation pooling the studies and testing for a treatment-by-study interaction was undertaken. A significant treatment-by-study interaction would indicate that the relative treatment differences were statistically different in the two studies and pooling would not be justified. Conversely, the lack of a treatment-by-study interaction would indicate the studies resulted in a similar treatment response and pooling would be justified.

When the two Phase III studies were pooled for the SRI analysis, the treatment-by-study interaction was >0.5. Likewise, for the target population of high disease activity, the treatment-by-study interaction was >0.7 suggesting that the high disease activity subgroup may be more homogenous and therefore have a more similar treatment effect between the studies than the population as a whole.

Given these considerations, it is reasonable and valid to pool the two studies and allows better precision for evaluation of subgroups.

Conditions

Lupus Erythematosus, Discoid

Study Groups

Baseline Health-Related Quality of Life (HRQOL)

Quality of life assessment tools were similar across the treatment groups and indicated that there was impairment in quality of life of subjects in the Low C+anti-dsDNA Population

Belimumab 1 mg/kg

Intervention Type: DRUG

Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.

Belimumab 10 mg/kg

Intervention Type: DRUG

Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.

Placebo

Intervention Type: OTHER

Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.

SLE Medication Usage at Baseline

All subjects in the Low C+anti-dsDNA Population

Belimumab 1 mg/kg

Intervention Type: DRUG

Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.

Belimumab 10 mg/kg

Intervention Type: DRUG

Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.

Placebo

Intervention Type: OTHER

Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.

Interventions

Belimumab 1 mg/kg

Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.

Intervention Type: DRUG

Belimumab 10 mg/kg

Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.

Intervention Type: DRUG

Placebo

Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of SLE by ACR criteria.
• Active SLE disease.
• Autoantibody-positive.
• On stable SLE treatment regimen.

Exclusion Criteria

• Pregnant or nursing
• Have received treatment with any B cell targeted therapy.
• Have received treatment with a biological investigational agent in the past year.
• Have received IV cyclophosphamide within 180 days of Day 0.
• Have severe lupus kidney disease.
• Have active central nervous system (CNS) lupus.
• Have required management of acute or chronic infections within the past 60 days.
• Have current drug or alcohol abuse or dependence.
• Have a historically positive test or test positive at screening for HIV, hepatitis B, or hepatitis C.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Human Genome Sciences Inc., a GSK Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

References

van Vollenhoven RF, Petri MA, Cervera R, Roth DA, Ji BN, Kleoudis CS, Zhong ZJ, Freimuth W. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012 Aug;71(8):1343-9. doi: 10.1136/annrheumdis-2011-200937. Epub 2012 Feb 15.

Reference Type: BACKGROUND

PMID: 22337213 (View on PubMed)

Other Identifiers

115030

Identifier Type: -

Identifier Source: org_study_id