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

NCT01268033 | Completed Phase 2

• 1 other identifier: I08013
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 24

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.

Conditions

Childhood Idiopathic Nephrotic Syndrome

Keywords

rituximab; idiopathic nephrotic syndrome; minimal change disease; focal and segmental glomerulosclerosis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• - dosing of rituximab for toxicity during and/or after infusion

  5 months

• - dosing of rituximab for pharmacokinetics

  5 months

• - dosing of lymphocyte

  5 months

• Pediatric Quality of life inventory

  5 months

Study Arms (2)

Rituximab

EXPERIMENTAL

two infusions of Rituximab - at the dose of 375 mg/m²

Drug: Rituximab

placebo

PLACEBO COMPARATOR

two infusions of placebo

Drug: Placebo

Interventions

Rituximab DRUG

two infusions - at the dose of 375 mg/m²- will be administered at one week of interval

Rituximab

Placebo DRUG

two infusions - at the dose of 375 mg/m² - will be administrered at one week of interval

placebo

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Limoges: lead
• Hoffmann-La Roche: collaborator

Study Sites (24)

Queen Fabiola Universitary Children's Hospital

Brussels, Brussels Capital, 1020, Belgium

Location

Chu Amiens

Amiens, Amiens, 80054, France

Location

Chu Besancon

Besançon, Besancon, 25030, France

Location

Chu Bordeaux

Bordeaux, Bordeaux, 33076, France

Location

Chu Brest

Brest, Brest, 29609, France

Location

CHU CAEN

Caen, Caen, 14033, France

Location

Chu Clermont Ferrand

Clermont-Ferrand, Clermont Ferrand, 63058, France

Location

Chu Grenoble

Grenoble, Grenoble, 38043, France

Location

Chu Lille

Lille, Lille, 59800, France

Location

Chu Limoges

Limoges, Limoges, 87042, France

Location

AP-HM - Hôpital La Timone

Marseille, Marseille, 13385, France

Location

Chu Montpellier

Montpellier, Montpellier, 34295, France

Location

Chu Nantes

Nantes, Nantes, 44033, France

Location

CHU NICE

Nice, Nice, 06202, France

Location

AP-HP - Hôpital Necker

Paris, Paris, 75015, France

Location

AP-HP - Hôpital Trousseau

Paris, Paris, 75571, France

Location

CHU REIMS - American Memorial Hospital

Reims, Reims, 51092, France

Location

Chu Rennes

Rennes, Rennes, 35000, France

Location

Chu Rouen

Rouen, Rouen, 76031, France

Location

Chu Saint Etienne

Saint-Etienne, Saint Etienne, 42055, France

Location

Chu Strasbourg

Strasbourg, Strasbourg, 67098, France

Location

Chu Toulouse

Toulouse, Toulouse, 31059, France

Location

Chu Tours

Tours, Tours, 37044, France

Location

Chu Nancy

Vandœuvre-lès-Nancy, Vandoeuvre Les Nancy, 54511, France

Location

Related Publications (1)

• Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.

  PMID: 39513526 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome; Nephrosis, Lipoid; Glomerulosclerosis, Focal Segmental

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Nephritis

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Vincent GUIGONIS, MD

  CHU Limoges

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2010
• First Posted: December 29, 2010
• Study Start: December 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: March 23, 2015

Record last verified: 2015-03

Locations

BE (1); FR (23)