Clinical trial NCT01268033: Efficacy of Rituximab For the Treatment of Calcineurin Inhibitors Dependent Nephrotic Syndrome During Childhood
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Childhood Idiopathic Nephrotic Syndrome
Keywords: rituximab
idiopathic nephrotic syndrome
minimal change disease
focal and segmental glomerulosclerosis
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2010-12-29
Enrollment: 26
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Proteinuria with relapse of nephrotic syndrome (Serum albumin < 30 g/L) within 5 months
timeFrame: 5 months
Secondary outcomes:
measure: - dosing of rituximab for toxicity during and/or after infusion
timeFrame: 5 months
measure: - dosing of rituximab for pharmacokinetics
timeFrame: 5 months
measure: - dosing of lymphocyte
timeFrame: 5 months
measure: Pediatric Quality of life inventory
timeFrame: 5 months
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Queen Fabiola Universitary Children's Hospital
city: Amiens
country: France
facility: Chu Amiens
city: Besancon
country: France
facility: Chu Besancon
city: Bordeaux
country: France
facility: Chu Bordeaux
city: Brest
country: France
facility: Chu Brest
city: Caen
country: France
facility: CHU CAEN
city: Clermont Ferrand
country: France
facility: Chu Clermont Ferrand
city: Grenoble
country: France
facility: Chu Grenoble
city: Lille
country: France
facility: Chu Lille
city: Limoges
country: France
facility: Chu Limoges
city: Marseille
country: France
facility: AP-HM - Hôpital La Timone
city: Montpellier
country: France
facility: Chu Montpellier
city: Nantes
country: France
facility: Chu Nantes
city: Nice
country: France
facility: CHU NICE
city: Paris
country: France
facility: AP-HP - Hôpital Necker
city: Paris
country: France
facility: AP-HP - Hôpital Trousseau
city: Reims
country: France
facility: CHU REIMS - American Memorial Hospital
city: Rennes
country: France
facility: Chu Rennes
city: Rouen
country: France
facility: Chu Rouen
city: Saint Etienne
country: France
facility: Chu Saint Etienne
city: Strasbourg
country: France
facility: Chu Strasbourg
city: Toulouse
country: France
facility: Chu Toulouse
city: Tours
country: France
facility: Chu Tours
city: Vandoeuvre les Nancy
country: France
facility: Chu Nancy
Study officials:
affiliation: CHU Limoges
name: Vincent GUIGONIS, MD
role: PRINCIPAL_INVESTIGATOR
References: