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.
Male and female 18 years and older who meet the American College of Rheumatology/EUropean League Against Rheumatism collaborative initiative (ACR/EULAR) classification criteria 2013 for systemic scleroderma.
Severe ILD at the baseline assessment i. with an extensive ILD on HRCT ≥20% according to Goh classification [10] ii. or with forced vital capacity of the predicted value (% FVC) ≤ 70%.
or ILD regardless of HRCT extension and at high risk of progression (age > 60 years, male gender, early cutaneous diffuse SSc (≤ 5 years), Afro-American or Afro-Caribbean ethnicity, anti-SCL70/Topoisomerase I autoantibody, or biological inflammation with CRP >= 5 mg/L).
or ILD regardless of HRCT extension and with progression criteria in the past 6-24 months before the initial assessment (based on INBUILD study): i. relative decline in the forced vital capacity of the predicted value (% FVC) >=10% ii. or relative decline in FVC of 5-10% associated with a relative decline in DLCO >= 15% iii. or relative decline in FVC of 5-10% associated with worsening of dyspnea or extension of ILD lesion on HRCT iv. or worsening of dyspnea with extension of HRCT opacities
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
Parallel
Rituximab
Drugone course of IV rituximab consisting of an infusion of 1000 mg rituximab (diluted in 500 mL of saline 0.9 % sodium chloride) will be given at day 1, day 15 and an infusion of 500 mg rituximab (in 500 mL of saline 0.9 % sodium chloride) at week 24;
Placebo
Drugone course of intravenous placebo of rituximab consisting of an infusion of 500 mL of saline (0.9% sodium chloride) infusion will be given at day 1, day 15 and week 24;
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.
Forced Vital Capacity in %
Change in % of predicted FVC (% FVC)
Forced Vital Capacity in mL
Change in FVC (mL)
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.
Progression free survival
First event considered
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