Efficacy and Safety of Obinutuzumab Versus Rituximab in Childhood Steroid Dependant and Frequent Relapsing Nephrotic Syndrome
Efficacy and Safety of Obinutuzumab Versus Rituximab in Childhood Steroid Dependant and Frequent Relapsing Nephrotic Syndrome : a Double-blind Multicenter Randomized Controlled Study
Assistance Publique - Hôpitaux de Paris
88 participants
Oct 18, 2023
INTERVENTIONAL
Conditions
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).
Eligibility
Inclusion Criteria11
- Age between 3 and 18 years
- Steroid dependant Nephrotic Syndrome defined as:
- or more relapses during steroids or within 2 weeks following discontinuation.
- 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:
- or more relapses within 6 months following first remission
- 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 Criteria15
- 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)
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
single infusion of Rituximab 375 mg/m2
single infusion of Obinutuzumab 300mg/1.73 m2
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05786768