A Prospective, Randomized, Double Blind, Placebo-controlled Phase II/III Study Evaluating the Efficacy of Rituximab in the Prevention of Relapse of Calcineurin Inhibitors Dependent Idiopathic Nephrotic Syndrome of Childhood
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 26
- 试验地点
- 24
- 主要终点
- Proteinuria with relapse of nephrotic syndrome (Serum albumin < 30 g/L) within 5 months
研究概览
简要总结
Background
Idiopathic nephrotic syndrome is a rare disease beginning during childhood and treated with immunosuppressants (i.e. steroids, mycophenolate mofetil, cyclophosphamide, cyclosporine).
Renal function of patients suffering from severe, steroid-dependent nephrotic syndrome with failure or toxic side effects of other immunosuppressant treatments is a major matter of concern.
Cyclosporine endangers renal parenchyma (fibrosis) in these patients who must take this treatment for years. At the same time, low doses of cyclosporine allow proteinuria to reappear, which provokes degradation of renal function by focal segmental glomerulosclerosis. Some recent data lead to the conclusion that Rituximab may be effective in such a disease, with a cyclosporin sparing effect.
Purpose
The aim of the study is to evaluate the efficacy of Rituximab versus placebo in the treatment of pediatric patients suffering from severe cyclosporine-dependent nephrotic syndrome.
Abstract Patients will be included in the study in a period of remission of proteinuria. Two infusions of Rituximab - at the dose of 375 mg/m²- or placebo will be administered at one week of interval. Other immunosuppressant treatments will be gradually tapered off with the same tapering pattern in both groups. In case of relapse of nephrotic syndrome, the blinding code will be broken. Rituximab will then be infused to patients having received placebo.
详细描述
After infusions of Rituximab or placebo, patients will be examined by their nephrologist on a monthly basis during five months. Follow up will be focused on proteinuria, albuminemia, lymphocyte phenotyping and Rituximab pharmacokinetics
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
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or Female patients over 2 and under 18 years, with an idiopathic nephrotic syndrome (NS)
- •Steroid Sensitive Nephrotic Syndrome (according to the French pediatric protocol).
- •Calcineurin inhibitor Dependent NS or NS for which anticalcineurin treatment has not been effective. Others immunosuppressive treatments (MMF) must have failed to control the disease activity.
- •Effective contraception for girls of childbearing age.
- •The patient is able to understand and has signed a written informed consent OR the parent or legal guardian is able to understand and has signed a written informed consent, which must be obtained prior to the initiation of any study procedure
排除标准
- •Terminal renal failure requiring dialysis/transplantation
- •Transcutaneous oxygen stauration < 97%
- •Clinical or Radiological brochopulmonar or pleural abnormality
- •Asymptomatic carrier of Hepatitis B virus our history of Hepatitis B
- •Contraindication to Rituximab (RTX)
- •Parents/patient refusing to participate in the study
研究组 & 干预措施
Rituximab
two infusions of Rituximab - at the dose of 375 mg/m²
干预措施: Rituximab (Drug)
placebo
two infusions of placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Proteinuria with relapse of nephrotic syndrome (Serum albumin < 30 g/L) within 5 months
时间窗: 5 months
Proteinuria with relapse of nephrotic syndrome (Serum albumin \< 30 g/L) within 5 months
次要结局
- Pediatric Quality of life inventory(5 months)
- - dosing of rituximab for toxicity during and/or after infusion(5 months)
- - dosing of rituximab for pharmacokinetics(5 months)
- - dosing of lymphocyte(5 months)