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

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.

Study Overview

• Status: Suspended
• Conditions: Steroid-Dependent Nephrotic Syndrome
• Intervention / Treatment: Drug: immunoglobulin IV

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.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75019
    • Robert Debré Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Rituximab (375 mg/m²); Single infusion of rituximab (375 mg/m²)
Experimental: Rituximab followed by 5 injections of immunoglobulin IV; 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	Drug: immunoglobulin IV; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	24 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Julien HOGAN, MD PhD, APHP

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2019
• Primary Completion (Actual): January 7, 2021
• Study Completion (Anticipated): November 4, 2022

Study Registration Dates

• First Submitted: June 6, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (Actual): June 18, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Syndrome; Nephrotic Syndrome; Nephrosis; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: P160905J; 2017-000826-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No