Efficacy of Rituximab For the Treatment of Calcineurin Inhibitors Dependent Nephrotic Syndrome During Childhood (NEPHRUTIX)
Primary Purpose
Childhood Idiopathic Nephrotic Syndrome
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Rituximab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Childhood Idiopathic Nephrotic Syndrome focused on measuring rituximab, idiopathic nephrotic syndrome, minimal change disease, focal and segmental glomerulosclerosis
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
Sites / Locations
- Queen Fabiola Universitary Children's Hospital
- Chu Amiens
- Chu Besancon
- Chu Bordeaux
- Chu Brest
- CHU CAEN
- Chu Clermont Ferrand
- Chu Grenoble
- Chu Lille
- Chu Limoges
- AP-HM - Hôpital La Timone
- Chu Montpellier
- Chu Nantes
- CHU NICE
- AP-HP - Hôpital Necker
- AP-HP - Hôpital Trousseau
- CHU REIMS - American Memorial Hospital
- Chu Rennes
- Chu Rouen
- Chu Saint Etienne
- Chu Strasbourg
- Chu Toulouse
- Chu Tours
- Chu Nancy
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Rituximab
placebo
Arm Description
two infusions of Rituximab - at the dose of 375 mg/m²
two infusions of placebo
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
- dosing of rituximab for toxicity during and/or after infusion
- toxicity during and/or after infusion
- dosing of rituximab for pharmacokinetics
- dosing of rituximab for pharmacokinetics
- dosing of lymphocyte
- lymphocyte phenotyping
Pediatric Quality of life inventory
Pediatric Quality of life inventory
Full Information
NCT ID
NCT01268033
First Posted
December 15, 2010
Last Updated
March 20, 2015
Sponsor
University Hospital, Limoges
Collaborators
Hoffmann-La Roche
1. Study Identification
Unique Protocol Identification Number
NCT01268033
Brief Title
Efficacy of Rituximab For the Treatment of Calcineurin Inhibitors Dependent Nephrotic Syndrome During Childhood
Acronym
NEPHRUTIX
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
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Limoges
Collaborators
Hoffmann-La Roche
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Childhood Idiopathic Nephrotic Syndrome
Keywords
rituximab, idiopathic nephrotic syndrome, minimal change disease, focal and segmental glomerulosclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab
Arm Type
Experimental
Arm Description
two infusions of Rituximab - at the dose of 375 mg/m²
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
two infusions of placebo
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
two infusions - at the dose of 375 mg/m²- will be administered at one week of interval
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
two infusions - at the dose of 375 mg/m² - will be administrered at one week of interval
Primary Outcome Measure Information:
Title
Proteinuria with relapse of nephrotic syndrome (Serum albumin < 30 g/L) within 5 months
Description
Proteinuria with relapse of nephrotic syndrome (Serum albumin < 30 g/L) within 5 months
Time Frame
5 months
Secondary Outcome Measure Information:
Title
- dosing of rituximab for toxicity during and/or after infusion
Description
- toxicity during and/or after infusion
Time Frame
5 months
Title
- dosing of rituximab for pharmacokinetics
Description
- dosing of rituximab for pharmacokinetics
Time Frame
5 months
Title
- dosing of lymphocyte
Description
- lymphocyte phenotyping
Time Frame
5 months
Title
Pediatric Quality of life inventory
Description
Pediatric Quality of life inventory
Time Frame
5 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vincent GUIGONIS, MD
Organizational Affiliation
CHU Limoges
Official's Role
Principal Investigator
Facility Information:
Facility Name
Queen Fabiola Universitary Children's Hospital
City
Brussels
ZIP/Postal Code
1020
Country
Belgium
Facility Name
Chu Amiens
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
Chu Besancon
City
Besancon
ZIP/Postal Code
25030
Country
France
Facility Name
Chu Bordeaux
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Chu Brest
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
CHU CAEN
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Chu Clermont Ferrand
City
Clermont Ferrand
ZIP/Postal Code
63058
Country
France
Facility Name
Chu Grenoble
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Chu Lille
City
Lille
ZIP/Postal Code
59800
Country
France
Facility Name
Chu Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
AP-HM - Hôpital La Timone
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Chu Montpellier
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Chu Nantes
City
Nantes
ZIP/Postal Code
44033
Country
France
Facility Name
CHU NICE
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
AP-HP - Hôpital Necker
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
AP-HP - Hôpital Trousseau
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
CHU REIMS - American Memorial Hospital
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
Chu Rennes
City
Rennes
ZIP/Postal Code
35000
Country
France
Facility Name
Chu Rouen
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Chu Saint Etienne
City
Saint Etienne
ZIP/Postal Code
42055
Country
France
Facility Name
Chu Strasbourg
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
Chu Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Chu Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Chu Nancy
City
Vandoeuvre les Nancy
ZIP/Postal Code
54511
Country
France
12. IPD Sharing Statement
Learn more about this trial
Efficacy of Rituximab For the Treatment of Calcineurin Inhibitors Dependent Nephrotic Syndrome During Childhood
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