Evaluation of Efficacy and Safety of Rituximab and Mycophenolate Mofetil Combination in Patients With Interstitial Lung Disease Related to Systemic Sclerosis
- Conditions
- Interstitial Lung Disease With Systemic Sclerosis
- Interventions
- Drug: Placebo
- Registration Number
- NCT06549231
- Lead Sponsor
- University Hospital, Tours
- Brief Summary
The goal of this clinical trial is to evaluate the efficacy on lung function after 24 weeks of rituximab + MMF combination comparatively to placebo + MMF combination in patients with SSc-ILD severe at the initial assessment or at high risk of progression.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 102
Not provided
- Known diagnosis of significant respiratory disorders (asthma, tuberculosis, aspergillosis, cystic fibrosis, idiopathic pulmonary fibrosis, sarcoidosis, smoking-related ILD), severe cardiomyopathy or a known severe heart failure as considered by the investigator
- Known diagnosis of group 1 precapillary pulmonary hypertension (mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg and pulmonary vascular resistance > 2 UWood and FVC ≥ 70% theoretical) or group 3 severe precapillary pulmonary hypertension (mPAP > 20 mmHg and PAWP ≤ 15 mmHg and pulmonary vascular resistance > 5 UWood, whatever the FVC)
- Concomitant medical or surgical disease, clinically significant as considered by the investigator, serious or unstable, acute or chronically progressive, or any condition that could affect the safety of the patient, in the opinion of the investigator
- Patient who cannot walk more than 100 meters
- Known MMF intolerance
- Initiation of a new therapy for SSc-ILD or with interruption / modification of therapy dosage within 4 weeks prior to baseline assessment
- Patient having already received a rituximab or MMF-based treatment line for SSc-ILD
- Known hypersensitivity to rituximab, to murine proteins, other excipients or sulphonamide antibiotics.
- Concomitant immunosuppressive treatments: >15 mg/day corticosteroids, azathioprine, cyclophosphamide, methotrexate, cyclosporine, tacrolimus, JAK inhibitors within 4 weeks prior to inclusion
- Treatment with monoclonal antibodies (such as, but not limited to, etanercept, adalimumab, efalizumab, infliximab, golimumab, certolizumab, tocilizumab) within 6 months prior to inclusion
- Patients on a lung transplant list
- Persons covered by articles L1121-5 to L1121-8 of the CSP (corresponding to all protected persons: pregnant women, parturients, nursing mothers, persons deprived of their liberty by judicial or administrative decision, minors, and persons subject to a legal protection measure: guardianship or trusteeship). Also, women of child-bearing potential (including female partners of sexually active men treated with mycophenolate) not using two reliable contraceptive methods and men not using a contraceptive method (condom), or women and men having a pregnancy project during the year following randomization
- Patients at high risk of infectious complications: Human Immunodeficiency Virus (HIV) positive or other known immunodeficiency syndromes, hepatitis B and C (HBV, HCV), COVID (within 3 month) or other known viral infection, infection requiring anti-infective treatment within 4 weeks of inclusion
- Patients with incomplete anti-SARS-CoV-2 vaccine regimen (according to current recommendations) and in this case, patient who has not receive treatment with anti SARS CoV2 therapeutic antibodies (ex : tixagévimab/cilgavimab).
- Concomitant participation in other interventional research with an investigational drug or medical device.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - Rituximab Rituximab -
- Primary Outcome Measures
Name Time Method Forced vital Capacity in % At 24 weeks The primary outcome is the change in Forced Vital Capacity (FVC) (in % predicted) from baseline to week 24 with measures at baseline, week 12 and week 24.
- Secondary Outcome Measures
Name Time Method Overall survival At 48 weeks King's Brief Interstitial Lung Disease questionnaire From baseline to weeks 24 and 48 15 questions about the impact of the disease on life. All answers are from 1 to 7. There is no maximum and minimum.
Living with pulmonary fibrosis impact questionnaire From baseline to weeks 24 and 48 21 questions to determine how pulmonary fibrosis affects quality of life.
Pharmacokinetic At Day 1, day 15, week 12, week 24 and week 48 Pharmacokinetic parameters of rituximab : half life in secondes
Forced Vital Capacity in mL From baseline to weeks 24 and 48 Change in FVC (mL)
Scleroderma Health Assessment questionnaire From baseline to weeks 24 and 48 23 questions divided into four groups related to symptoms of vascular, respiratory, gastrointestinal and musculoskeletal dysfunction
Forced Vital Capacity in % From baseline to weeks 48 Change in % of predicted FVC (% FVC)
Rodnan skin score From baseline to weeks 24 and 48 Change in modified Rodnan skin score (mRSS). This score assesses the extent of thickening at 17 points on the body, simply by palpating the skin. Thickening is from 0 to 3. 0 equals to normal skin thickness and 3 to severe thickening.
Living with pulmonary fibrosis symptom questionnaire From baseline to weeks 24 and 48 23 questions to evaluate symptoms of pulmonary fibrosis
Diffusing capacity for carbon monoxide From baseline to weeks 24 and 48 Changes in % of predicted diffusing capacity for carbon monoxide
Physical activity From baseline to week 24 Change in accelerometer-assessed physical activity based on heart rate
Progression free survival At 24 and 48 weeks First event considered
Chest image From baseline to week 48 Changes in HRCT chest images will be assessed by two thoracic radiologists expert in ILDs, who will score the extent of ILD and the severity of traction bronchiectasis. The ILD extent score will be estimated to the nearest 10% at three lung zones (delimited by the carina and the lowest inferior pulmonary vein for both lungs) and averaged between these 3 zones. Traction bronchiectasis scores will be scored between 0 and 3 (0=absence; 1=mild dilatation without tortuosity; 2=moderate dilatation, \< 6mm diameter, with tortuosity; 3=severe dilatation≥ 6mm) for the same three lung zones and averaged for the whole lungs.
Biological markers From baseline to week 48 Changes of biological markers related to B-cell depletion. Change in serum gamma globulin concentration as a percentage of serum proteins
Advers events From baseline to week 48 Analyze of all adverse events, especially serious infectious adverse events, occurring during treatment period
6 minutes walk test From baseline to weeks 24 and 48 Changes in the 6 minute walk test
Cumulative doses of corticosteroids At week 24 and week 48