Efficacy and Safety of Obinutuzumab Versus Rituximab in Childhood Steroid Dependant and Frequent Relapsing Nephrotic Syndrome

• Status: Not yet recruiting
• Trial end date: 2027-12-15
• Target enrollment: 0
• Participant gender: All

Summary

B-cell depletion with rituximab induces sustained remission in children with Steroid-Dependent or Frequent Relapsing Nephrotic Syndrome (SD/FRNS). However, most patients relapse after B-cell recovery and some do not achieve B-cell depletion. Obinutuzumab is a 2nd generation humanized monoclonal antiCD20 antibody, with enhanced B cell-depleting potential. It has been reported safe and efficient in different renal autoimmune diseases including childhood nephrotic syndrome. This double-blind, randomized multicenter study is designed to assess the efficacy and safety of a single infusion of low-dose obinutuzumab compared to a single infusion of rituximab in children with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Obinutuzumab; Rituximab

Criteria

Inclusion Criteria:

• Age between 3 and 18 years

• Steroid dependant Nephrotic Syndrome defined as:

• 2 or more relapses during steroids or within 2 weeks following discontinuation.

• 2 or more relapses including one under steroid-sparing agent (MMF, Calcineurin inhibitors, cyclophosphamide, levamisole) or within 6 months following treatment withdrawal

OR Frequent Relapsing Nephrotic Syndrome defined as:

• 2 or more relapses within 6 months following first remission

• 3 or more relapses within any 12-month period

• Last relapse within 3 months prior to inclusion

• In remission, defined as 3 consecutive urinary dipsticks without proteinuria, at the time of randomization

• Vaccination schedule in accordance with the current recommendations in France

• Informed consent from parents

Exclusion Criteria:

• Secondary cause of nephrotic syndrome (such as membranous nephropathy, IgA nephropathy, lupus nephritis)

• Primary or secondary steroid resistance nephrotic syndrome

• Prior treatment with Rituximab within 6 months

• Prior treatment with obinutuzumab at any time

• CD20+ B-cell count < 2.5%

• Patient with neutrophils < 1.5 G/L and/or platelets < 75 G/L

• GFR < 80 ml/min/1.73m2

• Weight <16kg

• History of severe infection such as tuberculosis, hepatitis B, hepatitis C or HIV infection or LEMP

• History of malignancy- Uncontrolled infection (viral, bacterial and fungal)

• Vaccination with a live vaccine within 4 weeks prior to assignment/randomization

• Known hyperprolinemia

• Hypersensitivity to the active substance (OBI or RTX) or to proteins of murine origin, or to any of the other excipients

• Pregnancy or breastfeeding or ability to become pregnant and refusal to use effective contraception during the 18 months following the study treatment (only 1 infusion of obinutuzumab/Rituximab at the beginning of the study)

• Patient without medical insurance coverage (beneficiary or legal)