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

Tracking Information
First Submitted Date ICMJE	December 15, 2010
First Posted Date ICMJE	December 29, 2010
Last Update Posted Date	March 23, 2015
Study Start Date ICMJE	December 2010
Actual Primary Completion Date	May 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 28, 2010)	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 Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01268033 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 28, 2010)	- 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 Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Efficacy of Rituximab For the Treatment of Calcineurin Inhibitors Dependent Nephrotic Syndrome During Childhood
Official Title ICMJE	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
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
Study Type ICMJE	Interventional
Study Phase	Phase 2; Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Childhood Idiopathic Nephrotic Syndrome
Intervention ICMJE	Drug: Rituximab two infusions - at the dose of 375 mg/m²- will be administered at one week of interval; Drug: Placebo two infusions - at the dose of 375 mg/m² - will be administrered at one week of interval
Study Arms	Experimental: Rituximab two infusions of Rituximab - at the dose of 375 mg/m² Intervention: Drug: Rituximab; Placebo Comparator: placebo two infusions of placebo Intervention: Drug: Placebo
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: December 28, 2010)	26
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	May 2014
Actual Primary Completion Date	May 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	2 Years to 18 Years (Child, Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Belgium, France
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01268033
Other Study ID Numbers ICMJE	I08013
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	University Hospital, Limoges
Study Sponsor ICMJE	University Hospital, Limoges
Collaborators ICMJE	Hoffmann-La Roche
Investigators ICMJE	Principal Investigator: Vincent GUIGONIS, MD CHU Limoges
PRS Account	University Hospital, Limoges
Verification Date	March 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP