EVALUATING THE MORPHOFUNCTIONAL EFFECTS OF ECULIZUMAB THERAPY IN PRIMARY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS: A PILOT, SINGLE ARM STUDY IN TEN PATIENTS WITH PERSISTENT HEAVY PROTEINURIA
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 13
- 主要终点
- 24hours proteinuria
研究概览
简要总结
Membranoproliferative glomerulonephritis (MPGN) is the third or fourth leading cause of end stage renal disease among the primary glomerulonephritis. Hyperactivation of the alternative complement pathway and familial forms for all types of MPGN have been reported suggesting that genetic abnormalities may play a predisposing role to the disease. In recent case reports Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex ,is a safe and effective therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Biopsy-proven primary MPGN
- •Creatinine clearance >20 ml/min per 1.73m2
- •24-hour proteinuria persistently exceeding 3,5g in adults or exceeding 40mg/h/m2 in children (or exceeding 2mg protein/mg creatinine in children spot urine samples)
- •Persistently low C3 levels in at least two consecutive evaluations
- •Persistently high sC5b9 levels (>1000 ng/ml) in at least two previous consecutive evaluations
- •Written informed consent (by parents or tutors if underage)
排除标准
- •Age ≥75 years
- •Secondary MPGN (evidence of infection, immunological disease including vasculitis, systemic diseases and proliferative disorders)
- •Evidence at kidney biopsy evaluation of severe chronic histological changes that very unlikely could benefit of eculizumab therapy
- •Concomitant steroid or immunosuppressive therapy for immuno-mediated disease
- •Pregnancy or lactating
- •Childbearing potential without effective contraception
- •Any clinically relevant condition that might affect completion of the study participation and/or confound study results
- •Inability to understand the potential risks and benefits of the study
- •Legal incapacity
研究组 & 干预措施
Eculizumab
Patient Body weight ≥40 kg: initial phase 900 mg weekly x 4 and maintenance phase 1200 mg at week 5; then 1200 mg every 2 weeks Patient Body weight 30 - <40 kg : initial phase 600 mg weekly x 2 and maintenance phase 900 mg at week 3; then 900 mg every 2 weeks
干预措施: Eculizumab (Drug)
结局指标
主要结局
24hours proteinuria
时间窗: Changes from baseline at week 1,12,24,36,48 and 72.
次要结局
- Time to disease progression.(Up 72 week.)
- Terminal complement complex (sC5b-9) levels(Changes from baseline at 1,2, 3, 4,12,24,36,48,52,56,60 and 72 week.)
- Glomerular filtration rate (GFR) measured by iohexol plasma clearance and estimated.(Changes from Baseline at 1,24, 48 and 72 week.)