Efficacy of Rituximab For the Treatment of Calcineurin Inhibitors Dependent Nephrotic Syndrome During Childhood

Phase 2

Completed

• Conditions: Childhood Idiopathic Nephrotic Syndrome
• Interventions: Drug: Placebo; Drug: Rituximab

• Registration Number: NCT01268033
• Lead Sponsor: University Hospital, Limoges

Brief Summary

Background

Idiopathic nephrotic syndrome is a rare disease beginning during childhood and treated with immunosuppressants (i.e. steroids, mycophenolate mofetil, cyclophosphamide, cyclosporine).

Renal function of patients suffering from severe, steroid-dependent nephrotic syndrome with failure or toxic side effects of other immunosuppressant treatments is a major matter of concern.

Cyclosporine endangers renal parenchyma (fibrosis) in these patients who must take this treatment for years. At the same time, low doses of cyclosporine allow proteinuria to reappear, which provokes degradation of renal function by focal segmental glomerulosclerosis. Some recent data lead to the conclusion that Rituximab may be effective in such a disease, with a cyclosporin sparing effect.

Purpose

The aim of the study is to evaluate the efficacy of Rituximab versus placebo in the treatment of pediatric patients suffering from severe cyclosporine-dependent nephrotic syndrome.

Abstract Patients will be included in the study in a period of remission of proteinuria. Two infusions of Rituximab - at the dose of 375 mg/m²- or placebo will be administered at one week of interval. Other immunosuppressant treatments will be gradually tapered off with the same tapering pattern in both groups. In case of relapse of nephrotic syndrome, the blinding code will be broken. Rituximab will then be infused to patients having received placebo.

Detailed Description

After infusions of Rituximab or placebo, patients will be examined by their nephrologist on a monthly basis during five months. Follow up will be focused on proteinuria, albuminemia, lymphocyte phenotyping and Rituximab pharmacokinetics

Study Timeline

• Study Start: 2010-12
• Study First Submitted: 2010-12-15
• Study First Submitted QC: 2010-12-28
• Study First Posted: 2010-12-29
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-20
• Last Update Posted: 2015-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• Male or Female patients over 2 and under 18 years, with an idiopathic nephrotic syndrome (NS)
• Steroid Sensitive Nephrotic Syndrome (according to the French pediatric protocol).

NEPHRUTIX

• Calcineurin inhibitor Dependent NS or NS for which anticalcineurin treatment has not been effective. Others immunosuppressive treatments (MMF) must have failed to control the disease activity.
• Effective contraception for girls of childbearing age.
• The patient is able to understand and has signed a written informed consent OR the parent or legal guardian is able to understand and has signed a written informed consent, which must be obtained prior to the initiation of any study procedure

Exclusion Criteria

• Terminal renal failure requiring dialysis/transplantation
• Transcutaneous oxygen stauration < 97%
• Clinical or Radiological brochopulmonar or pleural abnormality
• Asymptomatic carrier of Hepatitis B virus our history of Hepatitis B
• Contraindication to Rituximab (RTX)
• Parents/patient refusing to participate in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	two infusions of placebo
Rituximab	Rituximab	two infusions of Rituximab - at the dose of 375 mg/m²

Primary Outcome Measures

Name	Time	Method
Proteinuria with relapse of nephrotic syndrome (Serum albumin < 30 g/L) within 5 months	5 months	Proteinuria with relapse of nephrotic syndrome (Serum albumin \< 30 g/L) within 5 months

Secondary Outcome Measures

Name	Time	Method
- dosing of rituximab for toxicity during and/or after infusion	5 months	- toxicity during and/or after infusion
- dosing of rituximab for pharmacokinetics	5 months	- dosing of rituximab for pharmacokinetics
Pediatric Quality of life inventory	5 months	Pediatric Quality of life inventory
- dosing of lymphocyte	5 months	- lymphocyte phenotyping

Trial Locations

Locations (24)

Queen Fabiola Universitary Children's Hospital; 🇧🇪 Brussels, Belgium

Chu Amiens; 🇫🇷 Amiens, France

Chu Besancon; 🇫🇷 Besancon, France

Chu Bordeaux; 🇫🇷 Bordeaux, France

Chu Brest; 🇫🇷 Brest, France

CHU CAEN; 🇫🇷 Caen, France

Chu Clermont Ferrand; 🇫🇷 Clermont Ferrand, France

Chu Grenoble; 🇫🇷 Grenoble, France

Chu Lille; 🇫🇷 Lille, France

Chu Limoges; 🇫🇷 Limoges, France

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