Informations générales (source: ClinicalTrials.gov)
Rituximab From the First Episode of Minimal Change Nephrotic Syndrome for Preventing Relapse Risk in Adult Patients: a Multicenter Randomized Controlled Trial (RIFIREINS)
Interventional
Phase 2
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
juillet 2020
novembre 2023
26 avril 2025
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Ambroise Paré | AUDARD Vincent | 18/04/2025 07:56:37 | Contacter | ||
| AP-HP - Hôpital Bicêtre | AUDARD Vincent | 18/04/2025 07:56:37 | Contacter | ||
| AP-HP - Hôpital Bichat | AUDARD Vincent | 18/04/2025 07:56:37 | Contacter | ||
| AP-HP - Hôpital Europeen Georges Pompidou | AUDARD Vincent | 18/04/2025 07:56:37 | Contacter | ||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | AUDARD Vincent | 18/04/2025 07:56:37 | Contacter | ||
| AP-HP - Hôpital Necker-Enfants Malades | AUDARD Vincent | 18/04/2025 07:56:37 | Contacter | ||
| AP-HP - Hôpital Tenon | AUDARD Vincent | 18/04/2025 07:56:37 | Contacter | ||
| HOPITAL FOCH | MICHEL DELAHOUSSE | 05/05/2025 07:12:04 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AUDARD - 94320 - Créteil - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- Patient aged ≥ 18 years
- First episode of Minimal change nephrotic syndrome defined as albumin level < 30 g/L
and urine protein/creatinine ratio (UCPR) ≥ 300mg/mmol
- Biopsy-proven MCNS defined on renal biopsy examination by the presence of minimal
change glomerular lesions and absence of segmental sclerosis by light microscopy,
negative immunofluorescence, or presence of IgM deposits into the mesangium
- Signed informed consent to participate in the study
- Patients who are affiliated with the French health care system
- Patient aged ≥ 18 years
- First episode of Minimal change nephrotic syndrome defined as albumin level < 30 g/L
and urine protein/creatinine ratio (UCPR) ≥ 300mg/mmol
- Biopsy-proven MCNS defined on renal biopsy examination by the presence of minimal
change glomerular lesions and absence of segmental sclerosis by light microscopy,
negative immunofluorescence, or presence of IgM deposits into the mesangium
- Signed informed consent to participate in the study
- Patients who are affiliated with the French health care system
Previous administration of Rituximab therapy
- MCNS resulting from a secondary process (lymphoid disorders or malignant disease) or
potentially related to treatment known to be associated with MCNS occurrence
(Lithium, Interferon, non-steroidal anti-inflammatory drugs)
- Patients with acute infections or chronic active infections
- Positive serological screening test for HIV, B or C hepatitis
- Positive immunological tests for antinuclear and anti-DNA antibodies
- Usual contraindication to steroid or Rituximab
- Immunosuppressed patients, patients with a severe immune deficit
- Patients with hypersensitivity to a monoclonal antibody or biological agents
- Patients with a known allergy to steroid and its excipients or to Rituximab and its
excipients or to acetaminophen and its excipients or to cetirizine and its
excipients or to protein of murine origin
- Patients with other uncontrolled diseases, including drug or alcohol abuse, severe
psychiatric diseases, that could interfere with participation in the trial according
to the protocol,
- Patients who have white blood cell count ≤4,000/mm3,
- Patients who have platelet count ≤100,000/mm3,
- Patients who have haemoglobin level <9g/dL,
- Patients who have SGOT or SGPT or bilirubin level greater than 3 times the upper
limit of normal
- Patients who have serum creatinine level >150 µmol/l,
- Patients with active cancer or recent cancer (<5 years),
- Females of childbearing potential who don't have an effective method of birth
control during the study and during the next 12 months after treatment stop
- Women who are pregnant (positive βHCG at inclusion), or who plan to become pregnant
whilst in the trial
- Breastfeeding women
- Severe heart failure (New York Heart Association Class III and IV) or severe,
uncontrolled cardiac disease
- Patients who participate simultaneously in another interventional trial
- Patients not willing or able to comply with the protocol requirements
- Patients who are under tutorship or curatorship
Non randomization criteria
- Absence of complete remission after 8 weeks of treatment by steroids (CR is defined
as albumin level > 30 g/L and urine protein/creatinine ratio <30mg/mmol ).
- Positive βHCG at randomization (after 8 weeks of treatment by steroids)