Prospective Randomized Multicentric Open Label Study to Evaluate Rituximab Treatment for Idiopathic Membranous Nephropathy (IMN)
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
- Evaluation of efficacy of Rituximab associated with Non Immunosuppressive Symptomatic Treatment (NIST) in (IMN) in reducing the rate of proteinuria (patients with persistent urinary protein excretion rate ≥3,5g/24 h and albuminemia < 30g/l )
研究概览
简要总结
The Membranous Nephropathy is one of the most common cause of Nephrotic Syndrome of adults. In 2/3 of patients the cause of the disease is idiopathic. This can also be referred to as idiopathic membranous nephropathy (IMN).The most of these patients are treated by non immunosuppressive symptomatic treatment (NIST): antiproteinuric and antihypertensive blocking the rennin-angiotensine system. However, the patients resistant to antiproteinuric treatment risk to develop an end stage renal disease (ESRD).
Rituximab has been recently used in patients suffering of nephrotic syndrome related to IMN in four international studies. Rituximab appears effective and safe in reducing proteinuria in nearly 60% of patients.
The primary outcome of the investigators prospective randomized study is to determine whether or not the Rituximab associated with NIST is more effective than non immunologic symptomatic treatment alone in inducing long term remission of proteinuria.
详细描述
The IMN exposes patients to severe complications which engage the vital prognosis or Nephrotic Syndrome.
The development of well tolerated and effective pathogenesis linked therapies is needed to treat patients with idiopathic Membranous Nephropathy Rituximab, a monoclonal antibody (mAb) against the CD20 present on B cells, has been recently used in patients suffering of nephrotic syndrome related to IMN in four international studies. Rituximab appears effective and safe in reducing proteinuria in nearly 60% of patients.
However, no randomized controlled study has been published to date.
In a previous study, outcome of 28 patients treated with rituximab for idiopathic MN is analysed. Anti-PLA2R antibodies in serum and PLA2R antigen in kidney biopsy were assessed in 10 and 9 patients.
Proteinuria was significantly decreased by 56%, 62% and 87% at 3 months, 6 months and 12 months. At 6 months, 2 patients achieved full remission and 12 partial remission (overall renal response, 50%). At 12 months (n=23), complete remission was achieved in 6 patients and partial remission in 13 patients (overall renal response, 82,6%). Three patients suffered a relapse of nephrotic proteinuria 27 to 50 months after treatment. Univariate analysis suggested that the degree of renal failure (MDRD < 45/ml/min/1.73 m²) is an independent factor that predicts lack of response to rituximab. Anti-PLA2R antibodies were detected in serum in 10 patients, and PLA2R antigen in immune deposits in 8 of 9 patients. Antibodies became negative in all 5 responsive patients with available follow-up. In this retrospective study, a high rate of remission was achieved at 12 months after treatment.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 18 years old.
- •Idiopathic Membranous nephropathy proved by renal biopsy
- •Persistent urinary protein excretion rate ≥3,5g/24 h and albuminemia < 30g/l for at least 6 months with full dose of NIST
- •Patient receiving a non immunosuppressive conventional treatment (antiproteinuric and antihypertensive blocking the rennin-angiotensine system, lipid-lowering statin) since at least 6 months.
- •Patient has given its written consent
- •Patient with social coverage (excepting AME)
- •Use of an efficient contraception method for women in childbearing age.
排除标准
- •Secondary membranous nephropathy
- •Patient already in a clinical trial
- •Patient received an immunosuppressive treatment within 3 months before the study
- •Patient with chronic renal disease defined by estimated GFR by MDRD formula under 30ml/mn/1,73m²
- •Pregnancy and breastfeeding
- •HIV infection, HCV and HBV active infection
- •Severe or evolving infections.
- •Allergy or hypersensitivity to Rituximab or any component
研究组 & 干预措施
active comparator
Non Immunosuppressive Symptomatic Treatment (NIST). "No specific treatment" Converting Enzyme Inhibitor , Angiotensin II receptor antagonist, Anti-renin, Aldosterone antagonist diuretic, Beta blocker, Calcium inhibitor, statin.
干预措施: symptomatic treatment (Converting Enzyme inhibitor, Angiotensin II, Anti-renin, Aldosterone antagonist diuretic, Beta blocker, Calcium inhibitor, statin) (Drug)
experimental
NIST and Rituximab: 500 Mg and 100Mg in solution to be diluted for IV infusion (Mabthera®)
干预措施: experimental (Non Immunosuppressive Symptomatic Treatment (NIST) and Rituximab) (Drug)
结局指标
主要结局
Evaluation of efficacy of Rituximab associated with Non Immunosuppressive Symptomatic Treatment (NIST) in (IMN) in reducing the rate of proteinuria (patients with persistent urinary protein excretion rate ≥3,5g/24 h and albuminemia < 30g/l )
时间窗: 6 months
Evaluation of efficacy of Rituximab associated with Non Immunosuppressive Symptomatic Treatment (NIST) in (IMN) in reducing the rate of proteniuria
次要结局
- Evaluation of Rituximab tolerance in IMN(6 months)
- Lymphocyte CD19 dosing at month 3 and month 6.(6 months)
- Effect of Rituximab on the progression of chronic renal disease(6 months)
- serologic diagnosis with identification of anti-NEP and anti-PLA2R antibodies in IMN before and after treatment with Rituximab(6 months)
- genetic analysis(6 months)