Clinical Research Directory

The Clinical Application Study of Obinutuzumab in Pediatric Refractory Nephrotic Syndrome

Sponsor: Children's Hospital of Chongqing Medical University

Summary

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.

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