RITUXIMAB for Systemic sclerosis-associated interstitial lung disease|Systemic sclerosis

Inclusion criteria

• {"criterion_text":"- Adult patient (≥ 18 years old),"}
• {"criterion_text":"- Patient with a diagnosis of SSc, as defined by the ACR/EULAR 2013 criteria"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Woman of childbearing potential should have reliable contraception* for the 12 months’ duration of the study’s treatment and 12 months after last administration,"}
• {"criterion_text":"- Patient able to give written informed consent prior to participation in the study"}
• {"criterion_text":"- Affiliation to a social security scheme (profit or being entitled). AME is not accepted."}

Exclusion criteria

• {"criterion_text":"- Forced vital capacity < 40% of the predicted value"}
• {"criterion_text":"- Major surgery requiring hospitalization during the 4 weeks prior to screening or during screening"}
• {"criterion_text":"- Current alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening or during screening"}
• {"criterion_text":"- Diffusion capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) < 30% of the predicted value."}
• {"criterion_text":"- History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the RTX infusion"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Pregnancy or breastfeeding"}
• {"criterion_text":"- Participation in another interventional study or being in the exclusion period at the end of a previous study"}
• {"criterion_text":"- Contra-indication or anaphylaxis toward RTX"}
• {"criterion_text":"- Contra-indication to auxiliary medicinal products"}
• {"criterion_text":"- Cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening"}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Any live vaccine during the 28 days prior to screening or during screening"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Participants under court supervision, guardianship, or conservatorship"}
• {"criterion_text":"- Significant or uncontrolled medical disease which, in the investigator’s opinion, would preclude patient participation"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- History of serious recurrent or chronic infection"}
• {"criterion_text":"- History of progressive multifocal leukoencephalopathy (PML)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Known hypersensitivity to the active substance or to proteins of murine origin, or to any of the other excipients mentioned in the Composition section"}
• {"criterion_text":"- Severe heart failure (New York Heart Association (NYHA) Class IV) or severe uncontrolled heart disease"}

Primary endpoints

• {"endpoint_text":"- The absolute rate of changes in FVC from baseline to Month 18 of randomization.","definition_or_measurement_approach":"Absolute change in forced vital capacity (FVC) from randomization baseline to Month 18 (measured as absolute change in FVC)."}

Secondary endpoints

• {"endpoint_text":"- Safety and tolerability profile at 6, 12, and 18 months","definition_or_measurement_approach":"Safety and tolerability assessed at months 6, 12 and 18 (adverse events, laboratory and clinical safety assessments)."}
• {"endpoint_text":"- Disease-related mortality at 6, 12, and 18 months","definition_or_measurement_approach":"Disease-related deaths counted at months 6, 12 and 18."}
• {"endpoint_text":"- Progression-free survival (composite endpoint of mortality, transplant, treatment failure or decline in FVC >10% compared to baseline) at 6, 12, and 18 months","definition_or_measurement_approach":"Composite PFS defined as time to mortality, transplant, treatment failure or decline in FVC >10% vs baseline, evaluated at months 6, 12 and 18."}
• {"endpoint_text":"- Treatment failure (as determined by need for transplant or rescue therapy at 6, 12, and 18 months","definition_or_measurement_approach":"Treatment failure defined by requirement for transplant or rescue therapy, assessed at months 6, 12 and 18."}
• {"endpoint_text":"- Changes in FVC and diffusing capacity for carbon monoxide (DLCO) at 6, 12, and 18 months","definition_or_measurement_approach":"Absolute/relative changes in FVC and DLCO (corrected for hemoglobin) measured at months 6, 12 and 18."}
• {"endpoint_text":"- Change in 6-min walk test distance over 6, 12, and 18 months","definition_or_measurement_approach":"Change in 6-minute walk test distance measured at months 6, 12 and 18."}
• {"endpoint_text":"- Changes from baseline to 18 months in HRCT of chest images at 6, 12, and 18 months","definition_or_measurement_approach":"Radiological changes on HRCT compared to baseline assessed at months 6, 12 and 18."}
• {"endpoint_text":"- Scleroderma-specific endpoints (SSc disease activity revised CRISS, mRSS) at 6, 12, and 18 months","definition_or_measurement_approach":"SSc-specific measures including revised CRISS and modified Rodnan Skin Score (mRSS) at months 6, 12 and 18."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change in listed patient-reported outcome and QoL scores from baseline to months 6, 12 and 18."}
• {"endpoint_text":"- QALYs (estimated from EQ5D5Lscores) at 6, 12, and 18 months","definition_or_measurement_approach":"QALYs estimated from EQ-5D-5L scores at months 6, 12 and 18."}
• {"endpoint_text":"- Hospitalisation for respiratory cause over the duration of the trial","definition_or_measurement_approach":"Number/time of hospitalisations for respiratory causes during trial follow-up."}
• {"endpoint_text":"- Time to first hospitalisation for respiratory cause,","definition_or_measurement_approach":"Time from randomization to first respiratory-cause hospitalization."}
• {"endpoint_text":"- Time to first acute ILD exacerbation","definition_or_measurement_approach":"Time from randomization to first acute ILD exacerbation."}
• {"endpoint_text":"- Time to death","definition_or_measurement_approach":"Time from randomization to death (all-cause)."}

France

Earliest CTIS Part Ii Submission Date

14-04-2026

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

27

Number Of Sites

40

Number Of Participants

120

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France