Efficacy and Safety of Immunoglobulin Associated With Rituximab Versus Rituximab Alone in Childhood-Onset Steroid-dependent Nephrotic Syndrome

Study Overview
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Brief Summary
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Idiopathic Nephrotic Syndrome (INS) is the first glomerulopathy in children and 60% of the patients develop Steroid-Dependant Nephrotic Syndrome (SDNS). Recently, rituximab (RTX), a humanized anti-CD20 antibody depleting B cells demonstrated the ability to increase relapse free survival and to decrease the number of relapse and the need of other immunosuppressive drugs. However, the remission rate after 2 years is only 30 to 40%. The aim of the study is to study the ability of intravenous Immunoglobulin to improve remission rate in SDNS when added associated with Rituximab compared to a treatment by Rituximab alone.

Detailed Description
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Idiopathic Nephrotic Syndrome (INS) is the first glomerulopathy in children and 60% of the patients develop Steroid-Dependant Nephrotic Syndrome (SDNS). Depleting B cells demonstrated the ability to increase relapse free survival and to decrease the number of relapse and the need of other immunosuppressive drugs. However, the remission rate after 2 years is only 30 to 40%. The aim of the study is to study the ability of intravenous Immunoglobulin to improve remission rate in SDNS when added associated with Rituximab compared to a treatment by Rituximab alone.

Official Title
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Efficacy and Safety of Immunoglobulin Associated With Rituximab Versus Rituximab Alone in Childhood-Onset Steroid-dependent Nephrotic Syndrome

Conditions
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Steroid-Dependent Nephrotic Syndrome

Intervention / Treatment
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* Drug: immunoglobulin IV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Childhood onset nephrotic syndrome (first flair <18 years) ≥ 2 years old at inclusion Steroid-dependent: Patient with at least 2 relapses confirmed during the decay of corticosteroids or within 2 weeks following steroids discontinuation. Patient with at least 2 relapses including one under steroidsparing agent (MMF, Calcineurin inhibitors, cyclophosphamide, Levamisole) or within 6 months of treatment withdrawal. or with frequent relapses: · 2 or more relapses within 6 months after initial remission or 4 or more relapses within any 12-month period. with a relapse within 3 months prior to inclusion In remission: Protein-over-creatinine ratio ≤ 0.2g/g (≤ 0.02g/mmol) Exclusion Criteria: Patients with steroid-resistant nephrotic syndrome; Patients with genetic nephrotic syndrome; Patients previously treated with rituximab; Patients with no affiliation to a social security scheme (beneficiary or legal); Prior Hepatitis B, Hepatitis C or HIV infection; Pregnancy or breastfeeding. Patients with hyperprolinaemia, Known hypersensitivity to one of the study medication, Scheduled and not postponable injection of live attenuated vaccine Protected adults Patients with neutrophils < 1.5 G/L and/or platelets < 75 G/L

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 Arms : Rituximab (375 mg/m2) Rituximab (375 mg/m2) followed by 5 injections of immunoglobulin IV once a month during 5 months (2g/kg at M1, 1.5g/kg at M2 to M5, maximal dise 100g)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Rituximab (375 mg/m²)<br>Single infusion of rituximab (375 mg/m²) | |
| Experimental: Rituximab followed by 5 injections of immunoglobulin IV<br>Rituximab (375 mg/m²) followed by 5 injections of immunoglobulin IV once a month during 5 months (2g/kg at M1, 1.5g/kg at M2 to M5, maximal dose 100g). Treatment duration : 6 months | Drug: immunoglobulin IV<br>* 5 injections of immunoglobulin IV once a month during 5 months (2g/kg at M1, 1.5g/kg at M2 to M5, maximal dose 100g)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of the first relapse | Relapse is defined as a protein to creatinine ratio of 2g/g of creatinine (0.2 g/mmol) or higher | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first relapse |  | 24 months | 
| Number of relapse over a 24 months follow-up |  | 24 months | 
| Cumulative amount of corticosteroid over a 24 months follow-up |  | 24 months | 
| Adverse events in each arm |  | 24 months |