Safety and Efficacy Study of LymphoStat-B (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 safety and efficacy of 3 different doses of belimumab, administered in addition to standard therapy, in patients with active SLE disease.

Detailed Description
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The purpose of this study is to evaluate the safety and efficacy of three different doses of belimumab (1 mg/kg, 4 mg/kg, and 10 mg/kg), administered in addition to standard therapy, compared to placebo plus standard therapy in patients with active SLE disease. Patients were randomly assigned, following stratification by the screening SELENA SLEDAI score (4 to 7 versus ≥ 8), to 1 of the 4 study arms (3 active arms and 1 placebo arm plus standard therapy for SLE). All patients were to be dosed on Days 0, 14, and 28, then every 28 days for the remainder of 52 weeks. Patients completing the 52-week period could enter a 24-week open-label extension; belimumab patients received the same dose or were switched to 10 mg/kg at the investigator's discretion and former placebo patients received belimumab 10 mg/kg.

Official Title
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A Phase 2, Multi-Center, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety, Tolerability, and Efficacy of LymphoStat-B™ Antibody (Monoclonal Anti-BLyS Antibody) in Subjects With Systemic Lupus Erythematosus (SLE)

Conditions
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Lupus Erythematosus, Systemic

Intervention / Treatment
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* Drug: Placebo
* Drug: Belimumab 1 mg/kg
* Drug: Belimumab 4 mg/kg
* Drug: Belimumab 10 mg/kg


Participation Criteria
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Eligibility Criteria
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Primary Inclusion Criteria Clinical diagnosis of SLE Active SLE disease On a stable SLE treatment regimen History of measurable autoantibodies Primary Exclusion Criteria Received a non-FDA approved investigational agent within last 28 days Cyclosporin, intravenous immunoglobulin (IVIG) or plasmapheresis within last 90 days Active lupus nephritis requiring hemodialysis, cyclophosphamide (Cytoxan™), or high-dose prednisone (> 100 mg/day) within last 90 days Active central nervous system (CNS) lupus requiring therapeutic intervention within last 60 days History of renal transplant History of chronic infection that has been active within last 6 months, herpes zoster within last 90 days or any infection requiring hospitalization or intravenous medication within last 60 days History of hypogammaglobulinemia or immunoglobulin A (IgA) deficiency Human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 plus SOC<br> | Drug: Placebo<br>* Placebo IV plus standard therapy (SOC) for SLE; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, placebo patients who opted to participate received belimumab 10 mg/kg IV plus SOC every 28 days for an additional 24 weeks.<br>|
| Experimental: Belimumab 1 mg/kg plus SOC<br> | Drug: Belimumab 1 mg/kg<br>* Belimumab 1 mg/kg IV plus standard therapy (SOC) for SLE; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, patients who opted to participate either continued on the same dose of belimumab or may have been switched to belimumab 10 mg/kg at the investigator's discretion for an additional 24 weeks.<br>* Other names: BENLYSTA®;|
| Experimental: Belimumab 4 mg/kg plus SOC<br> | Drug: Belimumab 4 mg/kg<br>* Belimumab 4 mg/kg IV plus standard therapy (SOC) for SLE; belimumab 4 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, patients who opted to participate either continued on the same dose of belimumab or may have been switched to belimumab 10 mg/kg at the investigator's discretion for an additional 24 weeks.<br>* Other names: BENLYSTA®;|
| Experimental: Belimumab 10 mg/kg plus SOC<br> | Drug: Belimumab 10 mg/kg<br>* Belimumab 10 mg/kg IV plus standard therapy (SOC) for SLE; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 52 weeks in the double-blind period. In the open-label extension period, patients who opted to participate continued on belimumab 10 mg/kg for an additional 24 weeks.<br>* Other names: BENLYSTA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24. | SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. | Baseline, 24 weeks | 
| Time to First Mild/Moderate or Severe SLE Flare (SLE Flare Index) | The SLE Flare Index categorized SLE flare as mild or moderate or severe based on 5 variables: 1) change in SELENA SLEDAI score from the most recent assessment to current, 2) change in signs or symptoms of disease activity, 3) change in prednisone dosage, 4) use of new medications for disease activity or hospitalization, and 5) change in Physician's Global Assessment score, a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe). | 0 to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in SELENA SLEDAI Score at Week 52 | SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare | Baseline, 52 weeks | 
| Area Under the Curve (AUC) of SELENA SLEDAI Score at Week 52 | SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. The normalized AUC was created as the ratio of the area under the SELENA SLEDAI score curve divided by baseline score. | Baseline and every 4 to 8 weeks through Week 52 | 
| Percentage Change From Baseline in British Isles Lupus Activity Group (BILAG) Score at Week 52 | The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0. | Baseline, 52 weeks | 
| Area Under the Curve (AUC) of BILAG Score at Week 52 | The BILAG index is a clinical measure of lupus disease activity. BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E). The global BILAG score is the sum of the numerical scores in the 8 domains assigning A=9, B=3, C=1, D=0, E=0.The normalized AUC was created as the ratio of the area under the global BILAG score curve divided by baseline score. | Baseline and every 4 to 8 weeks through Week 52 | 
| Time to First Type A/B SLE Flare (as Defined Using BILAG) Over 52 Weeks | SLE flare indicates an increase in SLE disease activity. An SLE flare was a type A or B SLE flare (as defined using BILAG) compared with the previous visit. | 0 to 52 weeks | 
| Percentage of Patients With a Reduction in Prednisone Dose | Percentage of patients whose average prednisone dose has been reduced by ≥ 50% and/or has been reduced to ≤ 7.5 mg/day during Weeks 40 through 52 in patients receiving greater than 7.5 mg/day at baseline. | Baseline, weeks 40 to 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE