The Clinical Application Study of Obinutuzumab in Pediatric Refractory Nephrotic Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 100
- 试验地点
- 1
研究概览
简要总结
Primary nephrotic syndrome (PNS) in children is a clinical syndrome characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. The main subtypes include steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS), among which frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS) are relatively common in clinical practice. In recent years, anti-CD20 monoclonal antibodies, such as rituximab (RTX), have achieved remarkable efficacy in the treatment of pediatric NS, particularly in SDNS/FRNS and SRNS. However, a subset of children exhibit suboptimal responses to RTX or cannot continue its use due to allergic reactions.
Obinutuzumab (OBI) is a novel fully humanized anti-CD20 monoclonal antibody. Compared with RTX, OBI exhibits higher affinity for B cells and can bind to distinct CD20 epitopes, demonstrating stronger anti-B cell activity in vitro. Therefore, OBI has emerged as a potential alternative for patients who are unresponsive or intolerant to RTX [1].
Currently, OBI is a next-generation glycoengineered humanized anti-CD20 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) and apoptosis-inducing capabilities compared with RTX. Preliminary studies have shown its favorable efficacy and safety in adult systemic lupus erythematosus, refractory membranous nephropathy, transplant rejection, and pediatric SDNS/FRNS [2-3] and SRNS [4-5]. Clinical centers both domestically and internationally have already applied OBI in pediatric PNS patients who respond poorly to or are intolerant of RTX; however, no systematic studies have been conducted to date.
As a leading pediatric nephrology center in western China, affiliated with the National Clinical Medical Center, our institution plans to use OBI in children with refractory PNS. The goal is to provide a safer and more effective B cell-targeted therapy, with an expected complete or partial remission in over 80% of patients. This approach aims to significantly reduce dependency on steroids, cyclosporine, tacrolimus, and other drugs, offering children with kidney disease a more precise and safer treatment pathway. This study will be the first in China to systematically evaluate the efficacy and safety of obinutuzumab in pediatric refractory PNS-including steroid resistance, frequently relapsing or steroid-dependent cases resistant to standard second-line therapy-and compare it with RTX to determine its ability to maintain disease remission and facilitate steroid withdrawal.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnostic Criteria for Pediatric Primary Nephrotic Syndrome (PNS): Children aged 1 to 18 years who meet the following criteria:
- •Edema: Prominent edema, typically gravitational, affecting the eyelids and lower limbs.
- •Massive proteinuria: Defined as urine protein-to-creatinine ratio (UPCR) ≥ 200 mg/mmol or 24-hour urine protein ≥ 40 mg/m²·h.
- •Hypoalbuminemia: Serum albumin commonly below 25 g/L. Hyperlipidemia: Such as elevated total cholesterol.
- •Subtypes of Pediatric PNS:
- •Steroid-sensitive nephrotic syndrome (SSNS) Steroid-resistant nephrotic syndrome (SRNS)
- •SSNS can be further divided into steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS), with the following definitions:
- •SSNS: An important clinical subtype of PNS. Diagnostic criteria: patients receiving standard-dose prednisone or prednisolone (usually 1.5-2.0 mg/kg/day or 60 mg/m²/day, maximum 60 mg/day) achieve urine protein remission within 4 weeks.
- •SDNS: Initial response to glucocorticoid therapy is good, with proteinuria remission within 4 weeks. At least two relapses occur during steroid tapering or within 14 days after discontinuation, including relapses during dose reduction.
- •FRNS: Occurrence of three or more relapses within 12 months, or two or more relapses within 6 months. A relapse is defined as consecutive 3-day morning urine protein ≥ +++ by dipstick or UPCR ≥ 200 mg/mmol.
- •SRNS: Failure to achieve remission after 4 weeks of full-dose glucocorticoid therapy (prednisone or prednisolone 60 mg/m²/day or 1.5-2 mg/kg/day, maximum 60 mg/day) following PNS diagnosis, with persistent proteinuria (consecutive 3-day urine protein ≥ +++ by dipstick or UPCR ≥ 200 mg/mmol).
排除标准
- •Secondary PNS: Chronic kidney disease caused by underlying conditions such as Henoch-Schönlein purpura, systemic lupus erythematosus, hepatitis B, diabetes, hereditary nephritis, severe infections, tumors, or medications.
- •Exclusion criteria: Patients with significant steroid-related adverse effects, intolerance to steroids, or contraindications to steroid therapy.
研究者
Haiping Yang
Dr.
Children's Hospital of Chongqing Medical University