Efficacy and Safety of Belimumab for Prevention of Disease Flares in SLE Patients With Low Disease Activity
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 231
- 试验地点
- 1
- 主要终点
- Percentage of patients with disease flares
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
排除标准
- •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)
研究组 & 干预措施
Belimumab 2mg/kg
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.
干预措施: Belimumab (Biological)
Placebo
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.
干预措施: Placebo (Biological)
结局指标
主要结局
Percentage of patients with disease flares
时间窗: 52 weeks
Disease flare is defined by modified SELENA-SLEDAI SLE flare index (SFI).
次要结局
- SELENA-SLEDAI score at each visit(52 weeks)
- BiLAG score at each visit(52 weeks)
- Percentage of patients with mild/moderate flares(52 weeks)
- prednisone dose at each visit(52 weeks)
- Percentage of patients with major flares(52 weeks)
- Time to first disease flare(52 weeks)
- The percentage of patients achieving prednisone-free successfully(52 weeks)
- Number of participants with adverse events as assessed by CTCAE v4.0(52 weeks)