Efficacy and Safety of Belimumab in SLE Patients

Study Overview
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Brief Summary
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Systemic lupus erythematosus (SLE) is a chronic inflammatory systemic autoimmune disease. Recurrent relapses of disease and development of long-term organ damage are two key unsolved clinical problems. Belimumab is the only FDA-approved biological agent for SLE. Data showed that treatment with belimumab on the background of standard therapy was effective in active SLE patients. However, the efficacy of low-dose belimumab for prevention of disease flares in SLE patients with low disease activity is to be explored.

Detailed Description
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Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with the incidence of about 70/100,000 in China. Recurrent relapses of disease and development of long-term organ damage are two key unsolved clinical problems. Its pathogenesis is still unclear, but B cells have been confirmed to play a vital role in it. Belimumab, a B-lymphocyte stimulating factor (Blys) inhibitor, was the only FDA-approved biological agent for SLE. BLISS-52 showed that more active lupus patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 10 mg/kg (58% vs 46%, p=0·0024) than with placebo. But there was limited data about belimumab in SLE patients with low disease activity. Our previous study indicated that even these patients still have an annual flare rate of 30-40%. Therefore, we try to explore whether low-dose of belimumab could prevent the disease flares in SLE patients with low disease activity.

Official Title
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Efficacy and Safety of Belimumab for Prevention of Disease Flares in SLE Patients With Low Disease Activity

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Belimumab
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 years; Patients with low disease activity (score≤ 6 at screening on SLEDAI); no British Isles Lupus Assessment Group (BILAG) A and no more than one B; A stable treatment regimen with fixed doses of prednisone (≤ 20mg/day), antimalarial, or immunosuppressive drugs (azathioprine/mycophenolate mofetil/ methotrexate/ciclosporin/leflunomide/tacrolimus) for at least 30 days. Sign the informed consent; Exclusion Criteria: Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) > 2 times upper normal limits; Creatinine clearance rate < 60ml/min; Exposure to cyclophosphamide within past 6 months before screening; Exposure to any B cell targeted therapy (Rituximab/belimumab) within past 1 year before screening; History of Malignancy; History of herpes zoster with past 3 months before screening. Chronic HBV/HCV hepatitis； Current infections (HIV/tuberculosis)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belimumab 2mg/kg<br>Eligible patients were randomized in a 1:1 ratio to belimumab/placebo on the background of standard therapy. Belimumab 2mg/kg is administered intravenously at week 0, week 2, week 4 and then every 4 weeks until 48 weeks. | Biological: Belimumab<br>* Belimumab 2mg/kg intravenously<br>* Other names: BENLYSTA™;|
| Placebo Comparator: Placebo<br>Eligible patients were randomized in a 1:1 ratio to belimumab/placebo on the background of standard therapy. Placebo (normal saline) is administered intravenously at week 0, week 2, week 4 and then every 4 weeks until 48 weeks. | Biological: Placebo<br>* Placebo intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with disease flares | Disease flare is defined by modified SELENA-SLEDAI SLE flare index (SFI). | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with mild/moderate flares | Disease flare is defined by modified SELENA-SLEDAI SLE flare index (SFI). | 52 weeks | 
| Percentage of patients with major flares | Disease flare is defined by modified SELENA-SLEDAI SLE flare index (SFI). | 52 weeks | 
| Time to first disease flare | Time to first disease flare | 52 weeks | 
| prednisone dose at each visit | compare the prednisone dose at each visit | 52 weeks | 
| SELENA-SLEDAI score at each visit | compare the disease activity measured by SELENA-SLEDAI score at each visit | 52 weeks | 
| BiLAG score at each visit | compare the disease activity measured by BILAG score at each visit | 52 weeks | 
| The percentage of patients achieving prednisone-free successfully | the percentage of patients achieving prednisone-free successfully | 52 weeks | 
| Number of participants with adverse events as assessed by CTCAE v4.0 | the safety of belimumab | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Belimumab, Systemic Lupus Erythematosus, Disease flare