Rituximab from the first episode of Minimal Change Nephrotic Syndrome for preventing relapse risk in adult patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

29 Jul 2020 → ongoing

Decision date (initial)

2024-09-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

French Ministry of Health (PHRC-N 2017)

External identifiers

EU CT number

2024-516102-36-00

EudraCT number

2018-003437-15

ClinicalTrials.gov

NCT03970577

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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) to prevent relapse after 12 months of follow-up

Secondary objectives 4

1. The relapse rate (number of relapses per person-year) at 18 months after randomization
2. The type, frequency and the severity of adverse events and serious adverse events within 18 months of follow-up
3. The treatment burden that will be assessed at Week-4 before randomization, one week and 16 weeks after randomization
4. To assess the demographics, clinical and/or biological risk factors of relapse at 12 and 18 months of follow-up

Conditions and MedDRA coding

Minimal Change Nephrotic Syndrom

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patients aged ≥ 18 years
2. First episode of Minimal Change Nephrotic Syndrome defined as albumin level < 30 g/L and urine protein/creatinine ratio (UPCR) ≥ 300mg/mmol, OR
3. 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
4. Signed informed consent to participate in the study
5. Patients who are affiliated with the French health care system

Exclusion criteria 24

1. Previous administration of Rituximab therapy
2. Patient started on oral steroid therapy according to protocol dosage (1mg/kg) more than 4 weeks ago
3. 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)
4. Patients with acute infections or chronic active infections
5. Positive serological screening test for HIV, B or C hepatitis
6. Positive immunological tests for antinuclear and anti-DNA antibodies
7. Usual contraindication to steroid or Rituximab
8. Immunosuppressed patients, patients with a severe immune deficit
9. Patients with hypersensitivity to a monoclonal antibody or biological agents
10. 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
11. 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
12. Patients who have white blood cell count ≤4,000/mm3
13. Patients who have platelet count ≤100,000/mm3
14. Patient who have haemoglobin <9g/dL
15. Patients who SGOT or SGPT or bilirubin level greater than 3 times the upper limit of normal
16. Patients who have serum creatinine level >150 µmol/l,
17. Patients with active cancer or recent cancer (<5 years)
18. 18. 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
19. Women who are pregnant (positive βHCG at inclusion), or who plan to become pregnant whilst in the trial
20. Breastfeeding women
21. Severe heart failure (New York Heart Association Class III and IV) or severe or uncontrolled cardiac disease
22. Patients who participate simultaneously in another interventional trial
23. Patients not willing or able to comply with the protocol requirements
24. Patients who are under tutorship or curatorship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 4

1. The relapse rate at 18 months of follow-up after randomization
2. The type, frequency and the severity of adverse events (AEs) and serious adverse events (SAEs)
3. The treatment burden assessed with the Treatment Burden Questionnaire
4. To assess potential risk factors of relapse, the following explanatory variables will be recorded (demographics, clinical characteristics, biological variables, renal pathologic findings)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Vincent Audard

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Vincent Audard

Locations

1 EU/EEA country · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications