An Open-label, Non-randomized, 52-Week Study to Evaluate Treatment Holidays and Rebound Phenomenon After Treatment With Belimumab 10 mg/kg in Systemic Lupus Erythematosus Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Median Time to First SLE Flare Index (SFI)
研究概览
简要总结
This study will assess the effect of a 24-week withdrawal followed by a 28-week reintroduction of belimumab 10 mg/kg plus standard of care medications in subjects with stable low systemic lupus erythematosus (SLE) disease activity. Rebound phenomenon will be assessed for subjects who have permanently withdrawn from further belimumab treatment.
详细描述
This study will assess the effect of a 24-week withdrawal of belimumab followed by a 28-week reintroduction of belimumab 10 mg/kg plus standard of care medications on immunogenicity, markers of biological activity, efficacy, and safety in subjects with stable low systemic lupus erythematosus (SLE) disease activity. Additionally, this study will assess rebound phenomenon in subjects with any disease level of SLE who have permanently withdrawn from further belimumab treatment
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Received a minimun of 6 months therapy with with belimumab 10 mg/kg in their current SLE belimumab continuation study.
- •Be 18 years of age at the Day 0 visit.
- •Non-prenant, non-lactating females willing to comply with specific birth control requirements as set forth in the protocol.
- •Able to provide written informed consent to participate.
- •Subjects who wish to enroll in the control group and the group taking a 6 month belimumab treatment holiday will need a SELENA SLEDAI score of 3 or less after the minimum of 6 months belimumab therapy, as well as having C3 and C4 complement levels at or above the lower limit of the central laboratory reference range, and are on a stable SLE treatment regimen during the 30 day screening period prior to Day
- •Subjects who wish to enroll in the long-term discontinuation group have voluntarily withdrawn from their continuation studies.
排除标准
- •Subjects who have developed clinical evidence of significant, unstable or uncontrolled, acute or chronic diseases not due to SLE, or experienced an adverse event (AE) in their belimumab continuation study that could, in the opinion of the principle investigator, put the subject at undue risk.
- •Subjects who have developed any other medical diseases, laboratory abnormalities, or conditions that, in the opinion of the principle investigator, makes the subject unsuitable for the study.
研究组 & 干预措施
Treatment Holiday Group
Subjects in the Treatment Holiday Group will undergo a 6 month belimumab treatment holiday while remaining on standard of care SLE therapy, then re-start belimumab therapy for 6 months while receiving standard of care SLE therapy.
干预措施: Belimumab (Drug)
Control Group
Subjects in the Control Group will continue to receive monthly belimumab therapy, in addition to standard of care SLE therapy for 52 weeks.
干预措施: Belimumab (Drug)
结局指标
主要结局
Median Time to First SLE Flare Index (SFI)
时间窗: Up to 52 weeks
SFI Flare was defined as a mild/moderate or severe flare according to the modified Safety of Estrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA SLEDAI) SLE Flare Index (modified excluded severe flares from the SELENA SLEDAI flare assessment that were triggered only by an increase in SELENA SLEDAI score to \>12).Time to first SFI flare is defined as the number of days from Day 0 visit date to the date the participant has a flare (event date - Day 0 visit date + 1) in the 52 Week/Holiday phase; (event date - treatment re-start date + 1) in the Re-start Holiday phase. Day 0 visit date is defined as Day 0 from present study. Median time to first SFI flare is reported; estimated using the product-limit method.
次要结局
- Percentage Change From Baseline in Immunoglobulin(Baseline (Day 0 from parent studies); Day 0 and 8, 16, 24, 32, 40, 48 and 52 weeks)
- Percentage Change From Baseline in Autoantibody:Anti-double Stranded Deoxyribonucleic Acid (dsDNA)(Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 weeks)
- Rate of SLE Index Flare Per Subject Year(Up to 52 weeks)
- Median Time to First Severe SFI Flare(Up to 52 weeks)
- Number of Participants With Confirmed True Positive Belimumab Anti-drug Antibodies (ADA)(Up to 52 weeks)
- Number of Participants With Evidence of Rebound(Up to 24 weeks)
- Percentage Change From Baseline in Autoantibody: Antinuclear Antibody (ANA)(Baseline (Day 0 from parent studies); Day 0 and 24 and 52 weeks)
- Percentage Change From Baseline in Complement Levels(Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 weeks)
- Number of Days of Daily Prednisone Dose >=7.5 mg/Day and/or Increased by 25 Percent From Day 0 of This Study(Day 0 to Week 24; Week 24 to Week 52; Day 0 to Week 52)
- Percentage Change From Baseline in B Cell Subsets(Baseline (Day 0 from parent studies); Day 0 and 8, 16, 24, 32, 40 and 52 weeks)
- Percentage Change From 24 Week in B Cell Subsets: Treatment Holiday Group (Re-start Phase)(Week 24, 32, 40 and 52 weeks)
- SELENA SLEDAI Scores Change From Baseline(Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32,36, 40, 44, 48 and 52 weeks)
- Number of Days of Daily Prednisone Dose <=7.5 mg/Day and/or Decreased by 25 Percent From Day 0 of This Study(Day 0 to Week 24; Week 24 to Week 52; Day 0 to Week 52)