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

Childhood Idiopathic Nephrotic Syndrome Clinical Trial

— NEPHRUTIX  

Official title:

A Prospective, Randomized, Double Blind, Placebo-controlled Phase II/III Study Evaluating the Efficacy of Rituximab in the Prevention of Relapse of Calcineurin Inhibitors Dependent Idiopathic Nephrotic Syndrome of Childhood

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01268033
• Other study ID #: I08013
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: December 15, 2010
• Last updated: March 20, 2015
• Start date: December 2010
• Est. completion date: May 2014

Study information

• Verified date: March 2015
• Source: University Hospital, Limoges
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 18 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Childhood Idiopathic Nephrotic Syndrome
• Nephrosis
• Nephrosis, Lipoid
• Nephrotic Syndrome
• Syndrome

Intervention

Drug:
• Rituximab
two infusions - at the dose of 375 mg/m²- will be administered at one week of interval
• Placebo
two infusions - at the dose of 375 mg/m² - will be administrered at one week of interval

Locations

Country	Name	City	State
Belgium	Queen Fabiola Universitary Children's Hospital	Brussels
France	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	AP-HM - Hôpital La Timone	Marseille
France	Chu Montpellier	Montpellier
France	Chu Nantes	Nantes
France	CHU NICE	Nice
France	AP-HP - Hôpital Necker	Paris
France	AP-HP - Hôpital Trousseau	Paris
France	CHU REIMS - American Memorial Hospital	Reims
France	Chu Rennes	Rennes
France	Chu Rouen	Rouen
France	Chu Saint Etienne	Saint Etienne
France	Chu Strasbourg	Strasbourg
France	Chu Toulouse	Toulouse
France	Chu Tours	Tours
France	Chu Nancy	Vandoeuvre les Nancy

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Limoges	Hoffmann-La Roche

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proteinuria with relapse of nephrotic syndrome (Serum albumin < 30 g/L) within 5 months	Proteinuria with relapse of nephrotic syndrome (Serum albumin < 30 g/L) within 5 months	5 months	No
Secondary	- dosing of rituximab for toxicity during and/or after infusion	- toxicity during and/or after infusion	5 months	No
Secondary	- dosing of rituximab for pharmacokinetics	- dosing of rituximab for pharmacokinetics	5 months	No
Secondary	- dosing of lymphocyte	- lymphocyte phenotyping	5 months	No
Secondary	Pediatric Quality of life inventory	Pediatric Quality of life inventory	5 months	No