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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
University Hospital, Limoges
ClinicalTrials.gov Identifier:
NCT01268033
First received: December 15, 2010
Last updated: October 31, 2013
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Childhood Idiopathic Nephrotic Syndrome
Drug: Rituximab
Drug: Placebo
Phase 2
Phase 3

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

Resource links provided by NLM:


Further study details as provided by University Hospital, Limoges:

Primary Outcome Measures:
  • Proteinuria with relapse of nephrotic syndrome (Serum albumin < 30 g/L) within 5 months [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    Proteinuria with relapse of nephrotic syndrome (Serum albumin < 30 g/L) within 5 months


Secondary Outcome Measures:
  • - dosing of rituximab for toxicity during and/or after infusion [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    - toxicity during and/or after infusion

  • - dosing of rituximab for pharmacokinetics [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    - dosing of rituximab for pharmacokinetics

  • - dosing of lymphocyte [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    - lymphocyte phenotyping

  • Pediatric Quality of life inventory [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    Pediatric Quality of life inventory


Estimated Enrollment: 26
Study Start Date: December 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab
two infusions of Rituximab - at the dose of 375 mg/m²
Drug: Rituximab
two infusions - at the dose of 375 mg/m²- will be administered at one week of interval
Placebo Comparator: placebo
two infusions of placebo
Drug: Placebo
two infusions - at the dose of 375 mg/m² - will be administrered at one week of interval

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

Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01268033

Locations
Belgium
Queen Fabiola Universitary Children's Hospital
Brussels, Belgium, 1020
France
Chu Amiens
Amiens, France, 80054
Chu Besancon
Besancon, France, 25030
Chu Bordeaux
Bordeaux, France, 33076
Chu Brest
Brest, France, 29609
CHU CAEN
Caen, France, 14033
Chu Clermont Ferrand
Clermont Ferrand, France, 63058
Chu Grenoble
Grenoble, France, 38043
Chu Lille
Lille, France, 59800
Chu Limoges
Limoges, France, 87042
AP-HM - Hôpital La Timone
Marseille, France, 13385
Chu Montpellier
Montpellier, France, 34295
Chu Nantes
Nantes, France, 44033
CHU NICE
Nice, France, 06202
AP-HP - Hôpital Necker
Paris, France, 75015
AP-HP - Hôpital Trousseau
Paris, France, 75571
CHU REIMS - American Memorial Hospital
Reims, France, 51092
Chu Rennes
Rennes, France, 35000
Chu Rouen
Rouen, France, 76031
Chu Saint Etienne
Saint Etienne, France, 42055
Chu Strasbourg
Strasbourg, France, 67098
Chu Toulouse
Toulouse, France, 31059
Chu Tours
Tours, France, 37044
Chu Nancy
Vandoeuvre les Nancy, France, 54511
Sponsors and Collaborators
University Hospital, Limoges
Hoffmann-La Roche
Investigators
Principal Investigator: Vincent GUIGONIS, MD CHU Limoges
  More Information

No publications provided

Responsible Party: University Hospital, Limoges
ClinicalTrials.gov Identifier: NCT01268033     History of Changes
Other Study ID Numbers: I08013
Study First Received: December 15, 2010
Last Updated: October 31, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Limoges:
rituximab
idiopathic nephrotic syndrome
minimal change disease
focal and segmental glomerulosclerosis

Additional relevant MeSH terms:
Nephrotic Syndrome
Nephrosis, Lipoid
Nephrosis
Kidney Diseases
Urologic Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 17, 2014