Rituximab from the FIRst Episode of Idiopathic Nephrotic Syndrome

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2018-003437-15-FR
• Date of registration: 27/02/2019
• Prospective Registration: Yes
• Primary sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
• Public title: Rituximab from the FIRst Episode of Idiopathic Nephrotic Syndrome
• Scientific title: Rituximab from the FIRst Episode of Idiopathic Nephrotic Syndrome - RIFIREINS
• Date of first enrolment: 03/04/2019
• Target sample size: 148
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003437-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France

Contacts

• Name: DRCI - Hôpital Saint Louis
• Affiliation: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS

• Name: DRCI - Hôpital Saint Louis
• Affiliation: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS

Key inclusion & exclusion criteria

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 =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
- Patients affiliated with the French health care system.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 148
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- 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)
- 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
- Patients with a known allergy to steroid and its excipients or to Rituximab and its excipients
-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 ßHCG at inclusion), or who plan to become pregnant whilst in the trial
- Breastfeeding women
- Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
- Patients who participate simultaneously in another drug trial
- Patients not willing or able to comply with the protocol requirements
- Patients who are under tutorship or curatorship



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Minimal Change Nephrotic Syndrome (MCNS)
MedDRA version: 20.0 Level: LLT Classification code 10029168 Term: Nephrotic syndrome with lesion of minimal change glomerulonephritis System Organ Class: 100000004857

Intervention(s)

Trade Name: MabThera
Product Name: MabThera
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7

Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISONE
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Primary end point(s): Primary efficacy endpoint
The incidence of relapse will be analysed using survival analysis. A Cox proportional hazards model will be performed. The incidence of relapse at 12 months follow –up and its 95% confidence interval will be estimated in each study arm.

Main Objective: The main objective is to demonstrate, from initial episode of MCNS in adults, once complete remission occurred, the efficacy of Rituximab (two injections separated by one week 375mg/m2, with definitive steroids withdrawal after 9 weeks of treatment) compared to the standard regimen of oral steroid alone (progressively tapered within 24 weeks) to prevent relapse after 12 months of follow-up.

Timepoint(s) of evaluation of this end point: 12 months

Secondary Objective: The secondary objectives are to compare between the two arms:
- The relapse rate (number of relapses per person-year) at 12 and 18 months after randomization
- The time between randomization and relapse (with time points 12 and 18 months after randomization)
- The type, frequency and the severity of adverse events and serious adverse events during 12 and 18 months
- The treatment burden that will be assessed at Week-4 before randomization, one week and 16 weeks after randomization
- The demographics, clinical and/or biological risk factors of relapse at 12 and 18 months follow-up.

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints
The incidence of relapse at 18 months will be analysed using the same methodology than at 12 months time point.

Timepoint(s) of evaluation of this end point: 18 months

Secondary ID(s)

P170922J

Source(s) of Monetary Support

DGOS

Ethics review

Status: Approved
Approval date:
Contact: