NCT03970577: RIFIREINS

RItuximab From the FIRst Episode of Idiopathic Nephrotic Syndrome

Status unknown Phase 2 Last updated 13 July 2021

What this trial tests

Phase 2 trial testing Rituximab in Minimal Change Nephrotic Syndrome (MCNS) in 148 participants. Status unknown.

Timeline

29 July 2020

Primary endpoint
29 November 2023

29 November 2023

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	148
Start date	29 July 2020
Primary completion	29 November 2023
Estimated completion	29 November 2023
Sites	1 location across France

Drugs / interventions tested

• Rituximab — full drug profile →
• Prednisone (prednisone) — full drug profile →

Conditions studied

• Minimal Change Nephrotic Syndrome (MCNS) — all drugs for Minimal Change Nephrotic Syndrome (MCNS) →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

18 and older, any sex, with Minimal Change Nephrotic Syndrome (MCNS). Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Minimal change nephrotic syndrome (MCNS) is an acquired glomerular disease characterized by massive proteinuria occurring in the absence of glomerular inflammatory lesions or immunoglobulin deposits. MCNS represents a frequent cause of nephrotic syndrome (NS) in adults (10% to 25% of cases). The disease typically takes a chronic course characterized by frequent relapses. Until now, exclusive oral steroid therapy at the dose of 1mg/kg/day (max 80 mg/day) for a minimum of 4 weeks and a maximum of 16 weeks (as tolerated) constitutes the first line treatment of adults with MCNS. Despite of successful remission of initial episode, previous case series showed that 56%-76% of patients experience at least one relapse after steroid-induced remission. The recent MSN trial prospectively showed that 57.9% and 70% of adult patients were in complete remission (CR) after 4 and 8 weeks of oral steroids therapy (1mg/kg/day). Among them, 23.1% of patients displayed at least one relapse episode (after one year-follow-up). Although well tolerated, side effects are common in patients with prolonged and/or repeated courses of steroids and alternative regimens seem highly suitable to reduce the risk of subsequent relapse. Rituximab has recently emerged as a promising therapeutic option in patients with steroids dependent-MCNS. In a multicenter, double-blind, randomized, placebo-controlled trial in children with frequent relapse or with steroid dependent NS, the authors found that the median relapse free period was significantly longer in the Rituximab group than in the placebo group without significant differences concerning serious adverse events. To our knowledge, its use has never been investigated for the initial episode of MCNS with the aim to reduce the subsequent risk of relapse that is a major concern in the management of MCNS patients.

The main objective is to demonstrate, from initial episode of MCNS in adults, once complete remission has occurred, that the use of Rituximab (two injections separated by one week 375mg/m2, with definitive steroids withdrawal after 9 weeks of treatment) may reduce the risk of subsequent MCNS relapse after 12 months of follow-up and may be a safe and an efficient treatment regimen.

The study will be a single stage phase IIb, randomized, open-label, parallel group, in a 1:1 ratio, active controlled, multicenter trial testing the efficacy and safety of two injections of Rituximab separated by one week 375mg/m2 from initial episode of biopsy-proven MCNS in adults. Since Rituximab therapy (when initiated in a context of steroid dependency MCNS) seems to be more effective in patients with complete remission and because of recent data from MSN trial showing that 70% of patients were in complete remission of nephrotic syndrome after 8 weeks of steroids, we decided to maximize the potential benefit, to perform randomization of patients after 8 weeks of steroid treatment. A potential risk factor of relapse is the time of CR occurrence, and because some patients reach CR at 4 weeks and others at 8 weeks, a randomization (1:1) with minimization strategy will be done in order to balance this factor between arms. The primary endpoint will be the incidence of MCNS relapse during the 12 months following randomization defined by the recurrence of nephrotic syndrome (urine protein/creatinine ratio (UPCR) ≥ 300mg/mmol and decreased albumin level (\< 30 g/L) in a patient who was in complete remission.

Rituximab is currently considered as an effective therapeutic option to maintain remission in patients with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). The goal of this prospective study is to determine the potential interest of the use of Rituximab from the initial episode of MCNS to reduce the risk of subsequent relapse, that is a major concern in the management of MCNS patients.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Rituximab therapy for focal segmental glomerulosclerosis and minimal change disease in adults: a systematic review and meta-analysis.
   Hansrivijit P, Cheungpasitporn W, Thongprayoon C, Ghahramani N. · · 2020 · cited 47× · PMID 32293308 · DOI 10.1186/s12882-020-01797-7
2. B-Cell Dysregulation in Idiopathic Nephrotic Syndrome: What We Know and What We Need to Discover.
   Colucci M, Oniszczuk J, Vivarelli M, Audard V. · · 2022 · cited 39× · PMID 35140723 · DOI 10.3389/fimmu.2022.823204
3. Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies.
   Gauckler P, Matyjek A, Kapsia S, Marinaki S, et al · · 2025 · cited 23× · PMID 39431468 · DOI 10.1681/asn.0000000520
4. Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group.
   Mirioglu S, Daniel-Fischer L, Berke I, Ahmad SH, et al · · 2024 · cited 23× · PMID 38341276 · DOI 10.1093/ndt/gfae025
5. Optimizing the corticosteroid dose in steroid-sensitive nephrotic syndrome.
   Christian MT, Maxted AP. · · 2022 · cited 13× · PMID 33611671 · DOI 10.1007/s00467-021-04985-1
6. Early Rituximab as an Add-On Therapy in Children With the Initial Episode of Nephrotic Syndrome.
   Liu J, Deng F, Wang X, Liu C, et al · · 2024 · cited 9× · PMID 38707815 · DOI 10.1016/j.ekir.2024.02.1395
7. Protocol for an open-label, single-arm, multicentre clinical study to evaluate the efficacy and safety of rituximab in the first episode of paediatric idiopathic nephrotic syndrome.
   Liu J, Shen Q, Xie L, Wang J, et al · · 2022 · cited 4× · PMID 36223961 · DOI 10.1136/bmjopen-2022-064216
8. Contemporary Monoclonal Antibody Utilization in Glomerular Diseases.
   Mansour I, Murugapandian S, Tanriover B, Thajudeen B. · · 2023 · cited 1× · PMID 37448529 · DOI 10.1016/j.mayocpiqo.2023.04.009