A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of BIIB023 in Subjects With Lupus Nephritis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 276
- 试验地点
- 1
- 主要终点
- Percentage of Participants Who Achieve a Complete or Partial Renal Response at Week 52
研究概览
简要总结
The primary objective of the study is to assess the efficacy of BIIB023 as an add-on treatment to background therapy compared with placebo in combination with background therapy in the treatment of participants with active, biopsy-proven lupus nephritis. The secondary objectives of this study are to assess the safety and tolerability of BIIB023 compared with placebo in this study population.
详细描述
Participants who complete this study through Week 52 will be offered the option to enter an Extension study under a separate protocol 211LE202 (NCT0193089).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of systemic lupus erythematosus (SLE) according to current American College of Rheumatology (ACR) criteria. At least 4 ACR criteria must be documented, 1 of which must be a positive antinuclear antibody (ANA), anti Sm, or anti dsDNA antibody.
- •Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis with either active or active/chronic disease, confirmed by biopsy within 3 months prior to Screening. Participants are permitted to have co existing Class V lupus nephritis. If a renal biopsy has not been performed within 3 months of the Screening Visit, one can be performed during the Screening Period after all other eligibility criteria have been confirmed. The local histological diagnosis must be confirmed by the central study pathologist.
- •Must have proteinuria at Screening (from a 24 hour urine sample collection) defined as urinary protein:creatinine ratio (uPCR) >1.0 mg/mg.
排除标准
- •Retinitis, poorly-controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE at Screening
- •Estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m^2 (calculated using the abbreviated Modification of Diet in Renal Disease equation) or the presence of oliguria or end-stage renal disease requiring dialysis or transplantation
- •Subjects requiring dialysis within 12 months prior to Screening
- •History of renal transplant
- •Treatment with any biologic B-cell-depleting therapy (e.g., anti-CD20 [rituximab], anti-CD22 [epratuzumab], anti-BLyS/B-cell activating factor [e.g., briobacept, belimumab] therapy), or TACI-Ig within 12 months prior to Run-in Day
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Placebo
Placebo intravenous (IV) infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and mycophenolate mofetil (MMF)
干预措施: Placebo (Biological)
Placebo
Placebo intravenous (IV) infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and mycophenolate mofetil (MMF)
干预措施: mycophenolate mofetil (Drug)
Placebo
Placebo intravenous (IV) infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and mycophenolate mofetil (MMF)
干预措施: oral corticosteroids (Drug)
BIIB023 3 mg/kg
BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
干预措施: BIIB023 (Biological)
BIIB023 3 mg/kg
BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
干预措施: mycophenolate mofetil (Drug)
BIIB023 3 mg/kg
BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
干预措施: oral corticosteroids (Drug)
BIIB023 20 mg/kg
BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
干预措施: BIIB023 (Biological)
BIIB023 20 mg/kg
BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
干预措施: mycophenolate mofetil (Drug)
BIIB023 20 mg/kg
BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
干预措施: oral corticosteroids (Drug)
结局指标
主要结局
Percentage of Participants Who Achieve a Complete or Partial Renal Response at Week 52
时间窗: Week 52
Complete renal response is defined as: (1) urinary protein:creatinine ratio (uPCR) \< 0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline; from a 24 hour urine collection); and (2) estimated glomerular filtration rate (eGFR) within normal range. Partial renal response is defined as: (1) ≥ 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of \< 1.0 mg/mg if the Day 1 (Baseline) was ≤ 3.0 mg/mg, or, (b) uPCR \< 3.0 mg/mg if the Day 1 (Baseline) ratio was \> 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 \[Baseline\] or serum creatinine within normal range).
次要结局
- Percentage of Participants With uPCR > 3.0 mg/mg at Baseline Who Achieve uPCR <1.0 mg/mg at Week 52(Baseline (Day 1), Week 52)
- Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52(Week 52)
- Percentage of Participants Who Achieve Complete Renal Response at Week 52(Week 52)
- Time to Renal Response (Partial or Complete) in Participants Who Achieve Renal Response at Week 52(Baseline to Week 52)
- Percentage of Participants With Active Urinary Sediment at Baseline Who Have Inactive Urinary Sediment at Week 52(Baseline, Week 52)
- Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period(Week 12 to Week 56)
- Duration of Renal Response in Participants Who Achieve Partial or Complete Renal Response at Any Time During the Study(up to Week 52)
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period(Day 1 to Week 12)