A Study of Belimumab in Subjects With Systemic Lupus Erythematosus (SLE)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety, tolerability, and impact on quality of life of two different doses of belimumab administered in addition to standard therapy in subjects with active, autoantibody-positive systemic lupus erythematosus (SLE) disease.

Official Title
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A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Wk Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects With Systemic Lupus Erythematosus (SLE)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Placebo
* Drug: Belimumab 1 mg/kg
* Drug: Belimumab 10 mg/kg


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Clinical diagnosis of SLE by ACR criteria. Active SLE disease. Autoantibody-positive. On stable SLE treatment regimen. Key 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through Week 48.<br>|
| Experimental: Belimumab 1 mg/kg<br>Belimumab 1 mg/kg | Drug: Belimumab 1 mg/kg<br>* Belimumab 1 mg/kg IV plus standard therapy on Days 0, 14, 28, and every 28 days thereafter through Week 48.<br>* Other names: BENLYSTA™ (formerly LymphoStat-B™);|
| Experimental: Belimumab 10 mg/kg<br>Belimumab 10 mg/kg | Drug: Belimumab 10 mg/kg<br>* Belimumab 10 mg/kg IV plus standard therapy on Days 0, 14, 28, and every 28 days thereafter through Week 48.<br>* Other names: BENLYSTA™ (formerly LymphoStat-B™);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SLE Responder Index (SRI) Response Rate at Week 52 | Percentage of subjects with a ≥ 4 point reduction from baseline in SELENA SLEDAI score, and 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 compared with baseline. SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe). BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). | Baseline, 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Wk 52. |  | Baseline, 52 weeks | 
| Mean Change in Physician's Global Assessment (PGA) at Wk 24. | The PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity. | Baseline, 24 weeks | 
| Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Wk 24. | The SF-36 is a generic health related quality of life (HRQOL) measurement. The survey includes 36 questions grouped to 8 domains and 2 summary measures (physical and mental health component, PCS and MCS, respectively) assessing HRQOL. Responses are scored according to the SF-36v2™ manual. A score is calculated for each SF-36 domain based on the patient's response to each question within it. This is then transformed to a scale ranging from 0 (worst) to 100 (best) points. The PCS is norm-based where the mean=50 and standard deviation (SD)=10. Higher scores represent better physical health. | Baseline, 24 weeks | 
| Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52 |  | Baseline, Weeks 40 through 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autoimmune Diseases, Lupus, SLE, Systemic Lupus Erythematosus, Belimumab, Antibodies