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

NCT03560011 | Suspended Phase 2 DMC

• 2 other identifiers: P160905J2017-000826-36
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Steroid-Dependent Nephrotic Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (2)

Rituximab (375 mg/m²)

NO INTERVENTION

Single infusion of rituximab (375 mg/m²)

Rituximab followed by 5 injections of immunoglobulin IV

EXPERIMENTAL

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

Interventions

immunoglobulin IV DRUG

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)

Rituximab followed by 5 injections of immunoglobulin IV

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Childhood onset nephrotic syndrome (first flair \<18 years)
• 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.
• In remission: Protein-over-creatinine ratio ≤ 0.2g/g (≤ 0.02g/mmol)

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Robert Debre Hospital

Paris, 75019, France

Location

Related Publications (3)

• 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

• Chan EY, Yap DY, Colucci M, Ma AL, Parekh RS, Tullus K. Use of Rituximab in Childhood Idiopathic Nephrotic Syndrome. Clin J Am Soc Nephrol. 2023 Apr 1;18(4):533-548. doi: 10.2215/CJN.08570722. Epub 2023 Feb 22.

  PMID: 36456193 DERIVED

• 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.

  PMID: 32967877 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

gamma-Globulins

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Julien HOGAN, MD PhD

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: June 6, 2018
• First Posted: June 18, 2018
• Study Start: April 3, 2019
• Primary Completion: January 7, 2021
• Study Completion: November 4, 2022
• Last Updated: October 4, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

FR (1)