MAINRITSys : Rituximab vs placebo for maintenance in systemic sclerosis – interstitial lung disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Decision date (initial)

2026-05-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

French Ministry of Health National PHRC 2023

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate the efficacy of maintaining RTX as a maintenance strategy in individuals with stabilized SSc-ILD following RTX induction treatment.

Secondary objectives 4

1. to evaluate the safety profile of maintaining RTX in patients with SSc-ILD
2. to evaluate the efficacy profile of maintaining RTX in patients with SSc-ILD and SSc
3. to compare and evaluate patients’ quality of life, handicap, and patients reported outcomes between patients with SSc-ILD treated with maintained RTX and patients with SSc-ILD treated with a placebo
4. to estimate incremental cost utility of maintening RTX compared to placebo

Conditions and MedDRA coding

Patient with stabilized SSc-ILD (as defined by a decline of FVC ≤ 5%) following RTX induction treatment

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Adult patient (≥ 18 years old),
2. Patient with a diagnosis of SSc, as defined by the ACR/EULAR 2013 criteria
3. Patient with ILD identified on the basis of a HRCT, obtained within 12 months before screening, that showed fibrosis affecting at least 10% of the lungs
4. SSc-ILD induction with RTX, either twice 1000 mg two weeks apart, or 375 mg/m2 four times 4 weeks apart. The interval between the last induction dose and the first maintenance dose should be 6 months +/- 15 days.
5. Patient with stabilized SSc-ILD following RTX induction treatment as defined by the absence of worsening respiratory symptoms, an absolute decline of FVC of < 5% of the predicted value, an absence of absolute decline of DLCO (corrected for hemoglobin) of < 10% related to SSc-ILD, and absence of radiological evidence of disease progression on HRCT
6. All required vaccinations must have been carried out at least 4 weeks before D0. According to recommendations, prophylaxis against pneumocystis is recommended for scleroderma, but not mandatory
7. Woman of childbearing potential should have reliable contraception* for the 12 months’ duration of the study’s treatment and 12 months after last administration,
8. Patient able to give written informed consent prior to participation in the study
9. Affiliation to a social security scheme (profit or being entitled). AME is not accepted.

Exclusion criteria 26

1. Forced vital capacity < 40% of the predicted value
2. Major surgery requiring hospitalization during the 4 weeks prior to screening or during screening
3. Current alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening or during screening
4. Diffusion capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) < 30% of the predicted value.
5. History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the RTX infusion
6. Any of the following laboratory parameters: *AST or ALT above 2.5 upper limit normal range * Neutrophils <1.5x103/mL * Positive hepatitis B surface antigen (HBsAg) Participants who are HBsAg negative and hepatitis B core antibody (HBcAb) positive with no detectable hepatitis B virus (HBV) DNA are eligible but will require monthly HBV DNA monitoring until 12 months after the last dose of RTX or placebo. * Positive hepatitis C serology Participants with positive hepatitis C antibody test result with no detectable hepatitis C virus (HCV) RNA for at least 6 months after completion of antiviral therapy are eligible but will require monthly HCV RNA monitoring until 12 months after the last dose of RTX or placebo. * Hemoglobin below 7 g/dL * Platelet count below 50,000/L * Gammaglobulin levels < 4g/L
7. Pregnancy or breastfeeding
8. Participation in another interventional study or being in the exclusion period at the end of a previous study
9. Contra-indication or anaphylaxis toward RTX
10. Contra-indication to auxiliary medicinal products
11. Cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening
12. Active infection with SARS-CoV-2 or absence of COVID-19 vaccination within the last six months (this criteria will be updated at the time of submission to European Agency to be in adequation with national recommendation at the time of submission).
13. Any biologic therapy (including anti-CD20, anti-CD19, or anti-plasma cell) such as, but not limited to, belimumab, ustekinumab, anifrolumab, secukinumab, or atacicept during the 2 months prior to screening or during screening
14. Inhibitors of Janus-associated kinase (JAK), Bruton’s tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2), including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib or any investigational agent during the 2 months prior to screening or during screening
15. Any live vaccine during the 28 days prior to screening or during screening
16. High risk for clinically significant bleeding or any condition requiring plasmapheresis, IV immunoglobulin, or acute blood product transfusions during the 28 days prior the screening
17. Participants under court supervision, guardianship, or conservatorship
18. Significant or uncontrolled medical disease which, in the investigator’s opinion, would preclude patient participation
19. HIV infection : for participants with unknown HIV status (if the previous tests date more than 3 months), HIV testing will be performed locally at screening.
20. Tuberculosis (TB) infection: Testing for latent TB will be performed locally at screening if required by local regulations or in accordance with local clinical practice. Latent TB after completion of appropriate treatment is not exclusionary
21. Active infection of any kind, excluding fungal infection of the nail beds. Any major episode of infection that also fulfills any of the following criteria: * Requires hospitalization during the 8 weeks prior to screening or during screening * Requires treatment with IV antibiotics (or anti-infectives) during the 8 weeks prior to screening or during screening * Requires treatment with oral antibiotics (or anti-infectives) during the 2 weeks prior to screening or during screening * Antibiotics or anti-infectives given in the absence of a major episode of infection are not exclusionary.
22. History of serious recurrent or chronic infection
23. History of progressive multifocal leukoencephalopathy (PML)
24. History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, within the past 5 years. Participants with non-melanomatous carcinomas of the skin that have been treated or excised and have resolved are eligible.
25. Known hypersensitivity to the active substance or to proteins of murine origin, or to any of the other excipients mentioned in the Composition section
26. Severe heart failure (New York Heart Association (NYHA) Class IV) or severe uncontrolled heart disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The absolute rate of changes in FVC from baseline to Month 18 of randomization.

Secondary endpoints 14

1. Safety and tolerability profile at 6, 12, and 18 months
2. Disease-related mortality at 6, 12, and 18 months
3. Progression-free survival (composite endpoint of mortality, transplant, treatment failure or decline in FVC >10% compared to baseline) at 6, 12, and 18 months
4. Treatment failure (as determined by need for transplant or rescue therapy at 6, 12, and 18 months
5. Changes in FVC and diffusing capacity for carbon monoxide (DLCO) at 6, 12, and 18 months
6. Change in 6-min walk test distance over 6, 12, and 18 months
7. Changes from baseline to 18 months in HRCT of chest images at 6, 12, and 18 months
8. Scleroderma-specific endpoints (SSc disease activity revised CRISS, mRSS) at 6, 12, and 18 months
9. Change from baseline in health-related quality of life scores (St. George’s Respiratory Questionnaire (SGRQ), Short form (36) Health Questionnaire (SF-36), King’s Brief Interstitial Lung Disease (K-BILD), handicap questionnaires HAQ-DI, SHAQ, and patients reported outcomes questionnaires SSPRO and ScleroID) at 6, 12, and 18 months
10. QALYs (estimated from EQ5D5Lscores) at 6, 12, and 18 months
11. Hospitalisation for respiratory cause over the duration of the trial
12. Time to first hospitalisation for respiratory cause,
13. Time to first acute ILD exacerbation
14. Time to death

Investigational products

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

Test 1

Placebo 1

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

Dr Benjamin CHAIGNE

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Benjamin CHAIGNE

Locations

1 EU/EEA country · 40 investigational sites

By country

Investigational sites

Results and documents

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

Documents 6 files

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

Application history

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