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Efficacy and Safety of Immunoglobulin Associated With Rituximab Versus Rituximab Alone in Childhood-Onset Steroid-dependent Nephrotic Syndrome (RITUXIVIG)

Primary Purpose

Steroid-Dependent Nephrotic Syndrome

Status
Suspended
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
immunoglobulin IV
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Steroid-Dependent Nephrotic Syndrome

Eligibility Criteria

2 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Childhood onset nephrotic syndrome (first flair <18 years)
  • ≥ 2 years old at inclusion

  • Steroid-dependent:

    • Patient with at least 2 relapses confirmed during the decay of corticosteroids or within 2 weeks following steroids discontinuation.
    • Patient with at least 2 relapses including one under steroidsparing agent (MMF, Calcineurin inhibitors, cyclophosphamide, Levamisole) or within 6 months of treatment withdrawal.

  • or with frequent relapses:

    · 2 or more relapses within 6 months after initial remission or 4 or more relapses within any 12-month period.

  • with a relapse within 3 months prior to inclusion
  • In remission: Protein-over-creatinine ratio ≤ 0.2g/g (≤ 0.02g/mmol)

Exclusion Criteria:

  • Patients with steroid-resistant nephrotic syndrome;
  • Patients with genetic nephrotic syndrome;
  • Patients previously treated with rituximab;
  • Patients with no affiliation to a social security scheme (beneficiary or legal);
  • Prior Hepatitis B, Hepatitis C or HIV infection;
  • Pregnancy or breastfeeding.
  • Patients with hyperprolinaemia,
  • Known hypersensitivity to one of the study medication,
  • Scheduled and not postponable injection of live attenuated vaccine
  • Protected adults
  • Patients with neutrophils < 1.5 G/L and/or platelets < 75 G/L

Sites / Locations

  • Robert Debre Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Rituximab (375 mg/m²)

Rituximab followed by 5 injections of immunoglobulin IV

Arm Description

Single infusion of rituximab (375 mg/m²)

Rituximab (375 mg/m²) followed by 5 injections of immunoglobulin IV once a month during 5 months (2g/kg at M1, 1.5g/kg at M2 to M5, maximal dose 100g). Treatment duration : 6 months

Outcomes

Primary Outcome Measures

The occurrence of the first relapse
Relapse is defined as a protein to creatinine ratio of 2g/g of creatinine (0.2 g/mmol) or higher

Secondary Outcome Measures

Time to first relapse
Number of relapse over a 24 months follow-up
Cumulative amount of corticosteroid over a 24 months follow-up
Adverse events in each arm

Full Information

First Posted
June 6, 2018
Last Updated
October 1, 2021
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT03560011
Brief Title
Efficacy and Safety of Immunoglobulin Associated With Rituximab Versus Rituximab Alone in Childhood-Onset Steroid-dependent Nephrotic Syndrome
Acronym
RITUXIVIG
Official Title
Efficacy and Safety of Immunoglobulin Associated With Rituximab Versus Rituximab Alone in Childhood-Onset Steroid-dependent Nephrotic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Suspended
Why Stopped
Decision of Data Safety Monitoring Board
Study Start Date
April 3, 2019 (Actual)
Primary Completion Date
January 7, 2021 (Actual)
Study Completion Date
November 4, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Idiopathic Nephrotic Syndrome (INS) is the first glomerulopathy in children and 60% of the patients develop Steroid-Dependant Nephrotic Syndrome (SDNS). Recently, rituximab (RTX), a humanized anti-CD20 antibody depleting B cells demonstrated the ability to increase relapse free survival and to decrease the number of relapse and the need of other immunosuppressive drugs. However, the remission rate after 2 years is only 30 to 40%. The aim of the study is to study the ability of intravenous Immunoglobulin to improve remission rate in SDNS when added associated with Rituximab compared to a treatment by Rituximab alone.
Detailed Description
Idiopathic Nephrotic Syndrome (INS) is the first glomerulopathy in children and 60% of the patients develop Steroid-Dependant Nephrotic Syndrome (SDNS). Depleting B cells demonstrated the ability to increase relapse free survival and to decrease the number of relapse and the need of other immunosuppressive drugs. However, the remission rate after 2 years is only 30 to 40%. The aim of the study is to study the ability of intravenous Immunoglobulin to improve remission rate in SDNS when added associated with Rituximab compared to a treatment by Rituximab alone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Steroid-Dependent Nephrotic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
2 Arms : Rituximab (375 mg/m2) Rituximab (375 mg/m2) followed by 5 injections of immunoglobulin IV once a month during 5 months (2g/kg at M1, 1.5g/kg at M2 to M5, maximal dise 100g)
Masking
None (Open Label)
Masking Description
No masking
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rituximab (375 mg/m²)
Arm Type
No Intervention
Arm Description
Single infusion of rituximab (375 mg/m²)
Arm Title
Rituximab followed by 5 injections of immunoglobulin IV
Arm Type
Experimental
Arm Description
Rituximab (375 mg/m²) followed by 5 injections of immunoglobulin IV once a month during 5 months (2g/kg at M1, 1.5g/kg at M2 to M5, maximal dose 100g). Treatment duration : 6 months
Intervention Type
Drug
Intervention Name(s)
immunoglobulin IV
Intervention Description
5 injections of immunoglobulin IV once a month during 5 months (2g/kg at M1, 1.5g/kg at M2 to M5, maximal dose 100g)
Primary Outcome Measure Information:
Title
The occurrence of the first relapse
Description
Relapse is defined as a protein to creatinine ratio of 2g/g of creatinine (0.2 g/mmol) or higher
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Time to first relapse
Time Frame
24 months
Title
Number of relapse over a 24 months follow-up
Time Frame
24 months
Title
Cumulative amount of corticosteroid over a 24 months follow-up
Time Frame
24 months
Title
Adverse events in each arm
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Childhood onset nephrotic syndrome (first flair <18 years) ≥ 2 years old at inclusion Steroid-dependent: Patient with at least 2 relapses confirmed during the decay of corticosteroids or within 2 weeks following steroids discontinuation. Patient with at least 2 relapses including one under steroidsparing agent (MMF, Calcineurin inhibitors, cyclophosphamide, Levamisole) or within 6 months of treatment withdrawal. or with frequent relapses: · 2 or more relapses within 6 months after initial remission or 4 or more relapses within any 12-month period. with a relapse within 3 months prior to inclusion In remission: Protein-over-creatinine ratio ≤ 0.2g/g (≤ 0.02g/mmol) Exclusion Criteria: Patients with steroid-resistant nephrotic syndrome; Patients with genetic nephrotic syndrome; Patients previously treated with rituximab; Patients with no affiliation to a social security scheme (beneficiary or legal); Prior Hepatitis B, Hepatitis C or HIV infection; Pregnancy or breastfeeding. Patients with hyperprolinaemia, Known hypersensitivity to one of the study medication, Scheduled and not postponable injection of live attenuated vaccine Protected adults Patients with neutrophils < 1.5 G/L and/or platelets < 75 G/L
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julien HOGAN, MD PhD
Organizational Affiliation
APHP
Official's Role
Principal Investigator
Facility Information:
Facility Name
Robert Debre Hospital
City
Paris
ZIP/Postal Code
75019
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
32967877
Citation
Hogan J, Perez A, Sellier-Leclerc AL, Vrillon I, Broux F, Nobili F, Harambat J, Bessenay L, Audard V, Faudeux C, Morin D, Pietrement C, Tellier S, Djeddi D, Eckart P, Lahoche A, Roussey-Kesler G, Ulinski T, Boyer O, Plaisier E, Cloarec S, Jolivot A, Guigonis V, Guilmin-Crepon S, Baudouin V, Dossier C, Deschenes G. Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial. BMJ Open. 2020 Sep 23;10(9):e037306. doi: 10.1136/bmjopen-2020-037306.
Results Reference
derived

Learn more about this trial

Efficacy and Safety of Immunoglobulin Associated With Rituximab Versus Rituximab Alone in Childhood-Onset Steroid-dependent Nephrotic Syndrome

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