The Clinical Application Study of Obinutuzumab in Pediatric Refractory Nephrotic Syndrome (Obinutuzumab)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Nephrotic Syndrome

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400014
      • Chongqing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Pediatric Primary Nephrotic Syndrome

Description

Inclusion Criteria: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).

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Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the efficacy of obinutuzumab (OBI) in pediatric refractory nephrotic syndrome	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety of obinutuzumab (OBI) in pediatric refractory nephrotic syndrome, including SDNS/FRNS and SRNS.	12 months

Collaborators and Investigators

• Sponsor: Children's Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 21, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: HYang.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No