Evaluation of Efficacy and Safety of Rituximab and Mycophenolate Mofetil Combination in Patients With Interstitial Lung Disease Related to Systemic Sclerosis
NCT Number: NCT06549231
Acronym: EVER-ILD 3
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Interstitial Lung Disease With Systemic Sclerosis
Interventions: DRUG: Rituximab|DRUG: Placebo
Sponsor: University Hospital, Tours
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 102
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-11-15
Completion Date: 2028-11-15

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.

Primary Outcome Measures: Forced vital Capacity in %, 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., At 24 weeks
Secondary Outcome Measures: Forced Vital Capacity in %, Change in % of predicted FVC (% FVC), From baseline to weeks 48|Forced Vital Capacity in mL, Change in FVC (mL), From baseline to weeks 24 and 48|Rodnan skin score, 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., From baseline to weeks 24 and 48|Progression free survival, First event considered, At 24 and 48 weeks|Overall survival, At 48 weeks|Scleroderma Health Assessment questionnaire, 23 questions divided into four groups related to symptoms of vascular, respiratory, gastrointestinal and musculoskeletal dysfunction, From baseline to weeks 24 and 48|King's Brief Interstitial Lung Disease questionnaire, 15 questions about the impact of the disease on life. All answers are from 1 to 7. There is no maximum and minimum., From baseline to weeks 24 and 48|Living with pulmonary fibrosis symptom questionnaire, 23 questions to evaluate symptoms of pulmonary fibrosis, From baseline to weeks 24 and 48|Living with pulmonary fibrosis impact questionnaire, 21 questions to determine how pulmonary fibrosis affects quality of life., From baseline to weeks 24 and 48|Diffusing capacity for carbon monoxide, Changes in % of predicted diffusing capacity for carbon monoxide, From baseline to weeks 24 and 48|6 minutes walk test, Changes in the 6 minute walk test, From baseline to weeks 24 and 48|Physical activity, Change in accelerometer-assessed physical activity based on the number of steps per day, From baseline to week 24|Physical activity, Change in accelerometer-assessed physical activity based on heart rate, From baseline to week 24|Chest image, 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., From baseline to week 48|Biological markers, Changes of biological markers related to B-cell depletion. Change in the number of CD19 lymphocytes in absolute value/liter, From baseline to week 48|Biological markers, Changes of biological markers related to B-cell depletion. Change in the number of CD19 lymphocytes in percentage of leukocytes, From baseline to week 48|Biological markers, Changes of biological markers related to B-cell depletion. Change in serum gamma globulin concentration in grams/liter, From baseline to week 48|Biological markers, Changes of biological markers related to B-cell depletion. Change in serum gamma globulin concentration as a percentage of serum proteins, From baseline to week 48|Advers events, Analyze of all adverse events, especially serious infectious adverse events, occurring during treatment period, From baseline to week 48|Pharmacokinetic, Pharmacokinetic parameters of rituximab : volume of distribution in liter, At Day 1, day 15, week 12, week 24 and week 48|Pharmacokinetic, Pharmacokinetic parameters of rituximab : clearance in mili liter per minute, At Day 1, day 15, week 12, week 24 and week 48|Pharmacokinetic, Pharmacokinetic parameters of rituximab : half life in secondes, At Day 1, day 15, week 12, week 24 and week 48|Cumulative doses of corticosteroids, At week 24 and week 48