A Prospective, Randomized, Active Controlled, Parallel Group, Multi-center Trial to Assess the Efficacy and Safety of Mycophenolate Mofetil (MMF) in Inducing Response and Maintaining Remission in Subjects With Lupus Nephritis.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 370
- 主要终点
- Induction Phase: Number of Patients Showing Treatment Response
研究概览
简要总结
This 2 arm study assessed the efficacy of Mycophenolate Mofetil (MMF; CellCept) compared to cyclophosphamide in inducing a response in patients with lupus nephritis, and the long term efficacy of MMF compared to azathioprine in maintaining remission and renal function. Patients were randomized to receive either MMF (1.5 g twice daily [bid]) or cyclophosphamide (0.5-1.0 g/m^2 in monthly pulses) in the induction phase. Those patients meeting criteria for response were re-randomized for entry into the maintenance phase, to receive either MMF (1 g bid) or azathioprine (2 mg/kg/day).
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
- None
入排标准
- 年龄范围
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •male or female patients, 12-75 years of age;
- •diagnosis of systemic lupus erythematosus;
- •kidney biopsy within 6 months of study, with histological diagnosis of lupus nephritis;
- •laboratory evidence of active nephritis.
排除标准
- •continuous dialysis starting >2 weeks before randomization into induction phase, and/or with an anticipated duration of >8 weeks;
- •previous or planned kidney transplant;
- •other clinically significant active medical conditions.
研究组 & 干预措施
Induction Phase: Mycophenolate mofetil
Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24 weeks of the Induction Phase.
干预措施: Mycophenolate mofetil (MMF) (Drug)
Induction Phase: Mycophenolate mofetil
Participants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24 weeks of the Induction Phase.
干预措施: Corticosteroid (Drug)
Induction Phase: Cyclophosphamide
Participants received monthly infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.
干预措施: Cyclophosphamide (Drug)
Induction Phase: Cyclophosphamide
Participants received monthly infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.
干预措施: Corticosteroid (Drug)
Maintenance Phase: Mycophenolate mofetil
Participants received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.
干预措施: Mycophenolate mofetil (MMF) (Drug)
Maintenance Phase: Mycophenolate mofetil
Participants received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.
干预措施: Placebo to Azathioprine (Drug)
Maintenance Phase: Mycophenolate mofetil
Participants received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.
干预措施: Corticosteroid (Drug)
Maintenance Phase: Azathioprine
Participants received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
干预措施: Azathioprine (Drug)
Maintenance Phase: Azathioprine
Participants received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
干预措施: Placebo to Mycophenolate mofetil (Drug)
Maintenance Phase: Azathioprine
Participants received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
干预措施: Corticosteroid (Drug)
结局指标
主要结局
Induction Phase: Number of Patients Showing Treatment Response
时间窗: 24 weeks
Treatment response was adjudicated by a blinded clinical endpoints committee (CEC) and defined as: a) Decrease in proteinuria, defined as a decrease in the urine protein to creatinine ratio (UPCr) to \<3 in subjects with baseline proteinuria ≥3 UPCr or a decrease in the UPCr by ≥50% in subjects with proteinuria \<3 UPCr at Baseline, and b) Stabilization of serum creatinine or improvement. UPCr were derived from the 24 hour urine collection. Patients who did not show a treatment response at Week 24 or who withdrew earlier than Week 24 were considered non-responders.
Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval
时间窗: From the start of the Maintenance Phase to Month 36
Treatment Failure was adjudicated by a clinical endpoints committee and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to treatment failure for each patient. The data presented are the percentage of participants who were treatment-failure free at each time interval as estimated by Kaplan-Meier.
次要结局
- Induction Phase: Number of Participants Achieving Complete Remission(24 weeks)
- Induction Phase: Change From Baseline to Week 24 in Serum Creatinine(Baseline, Week 24)
- Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein(Baseline, Week 24)
- Induction Phase: Change From Baseline to Week 24 in Serum Albumin(Baseline, Week 24)
- Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score(Baseline, 24 weeks)
- Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores(Baseline and 24 weeks)
- Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Deaths(From the start of the Maintenance Phase to Month 36)
- Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With End-stage Renal Disease (ESRD)(From the start of the Maintenance Phase to Month 36)
- Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With Sustained Doubling of Serum Creatinine(From the start of the Maintenance Phase to Month 36)
- Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval(From the start of the Maintenance Phase to Month 36)
- Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy(From the start of the Maintenance Phase to Month 36)
- Maintenance Phase: Participants With Major Extra-renal Flare(From the start of the Maintenance Phase to Month 36)