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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Nephroti

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 Summary: 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
Sponsor: University Hospital, Limoges

Current Primary Outcome: Proteinuria with relapse of nephrotic syndrome (Serum albumin < 30 g/L) within 5 months [ Time Frame: 5 months ]

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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • - dosing of rituximab for toxicity during and/or after infusion [ Time Frame: 5 months ]
    - toxicity during and/or after infusion
  • - dosing of rituximab for pharmacokinetics [ Time Frame: 5 months ]
    - dosing of rituximab for pharmacokinetics
  • - dosing of lymphocyte [ Time Frame: 5 months ]
    - lymphocyte phenotyping
  • Pediatric Quality of life inventory [ Time Frame: 5 months ]
    Pediatric Quality of life inventory


Original Secondary Outcome: Same as current

Information By: University Hospital, Limoges

Dates:
Date Received: December 15, 2010
Date Started: December 2010
Date Completion:
Last Updated: March 20, 2015
Last Verified: March 2015