A Phase 2 interventional study of Mycophenolate Mofetil and Placebo in Systemic Sclerosis With Lung Involvement, Systemic Sclerosis and Interstitial Lung Disease, sponsored by Centre hospitalier de l'Université de Montréal (CHUM). Recruiting at 3 sites in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.
Sponsored by Centre hospitalier de l'Université de Montréal (CHUM) · Phase 2, Interventional, and Other
The goal of this pilot study is to assess the feasibility of a larger study on the efficacy of mycophenolate mofetil in people diagnosed with systemic sclerosis with mild lung involvement. Participants will be recruited over 12 months at 3 academic centers and assigned randomly to receive either mycophenolate mofetil or placebo, a look-alike substance that contains no active drug, for 96 weeks.
Background: Systemic sclerosis (SSc, scleroderma) is a rare but life-threatening systemic autoimmune disease characterized by microvasculopathy, serum autoantibodies, inflammation and fibrosis of the skin and internal organs. Early rapidly progressive SSc remains the most lethal autoimmune rheumatic disease, with over 60% mortality at 5 years in high-risk patients. Interstitial lung disease (ILD) is the leading cause of SSc-related mortality and affects over half of SSc patients. SSc-ILD is currently treated with immunosuppressive and anti-fibrotic drugs, with the first-line treatment being mycophenolate mofetil (MMF), although treatments have modest benefits when initiated in advanced stages of disease. Emerging data suggest that earlier treatment, when lung function is still normal despite evidence of ILD on computed tomography scan ("subclinical SSc-ILD"), may lead to improved outcomes, suggesting a window of treatment opportunity.
Research Aims: The goal of the proposed pilot RCT is to establish the feasibility of a phase III RCT that will assess the efficacy of MMF in subclinical SSc-ILD. Specifically, we aim to:
Methods: Participants will be adults with SSc, ILD diagnosed within the past 3 years and a normal forced vital capacity (≥ 80%). Participants will be recruited over 12 months at 3 academic centers affiliated to the Canadian Scleroderma Research Group. Eligible participants will be assigned using stratified randomization to receive either MMF (up to 2 grams daily) or placebo for 96 weeks. The primary feasibility outcome will be the rate of recruitment per site over 12 months. A Bayesian approach will be used to estimate the probability of reaching the target sample size based on observed recruitment rates, with decision rules to continue, adapt, or stop the trial. Data collected on the primary clinical efficacy outcome (annual rate of decline in forced vital capacity over 96 weeks) will be used to inform the analysis of the phase III trial (as an informative prior) through a Bayesian inference framework.
Exclusion Criteria:
Use of medications with putative lung disease-modifying properties:
Any contraindication to MMF, including:
2 to 4 capsules of mycophenolate mofetil twice daily.
Drug: Mycophenolate Mofetil
2 to 4 capsules of placebo twice daily.
Other: Placebo
The participant will receive 500 mg to 1000 mg twice daily of mycophenolate mofetil administered orally for 96 weeks. The dose scheduling will be as follow: Weeks 1 and 2: 500 mg twice a day Weeks 3 and 4: 750 mg twice a day Weeks 5 to 96: 1000 mg twice a day
The participant will receive 500 mg to 1000 mg twice daily of placebo administered orally for 96 weeks. The dose scheduling will be as follow: Weeks 1 and 2: 500 mg twice a day Weeks 3 and 4: 750 mg twice a day Weeks 5 to 96: 1000 mg twice a day
Total number of potentially eligible patients identified per site
Time frame: Over one year
Proportion of potentially eligible patients who provide consent per site
Time frame: Over one year
Proportion of consented participants who meet the eligibility criteria per site
Time frame: Over one year
Monthly rate of randomized participants per site
Time frame: Over one year
Adherence to treatment as assessed by Participant Dosing Diaries
Time frame: From the first dose to the last dose taken for each participant, up to 96 weeks
Drug adherence rate as assessed by Pharmacy Accountability Logs
Time frame: From the first dose to the last dose taken for each participant, up to 96 weeks
Adherence to the study protocol as assessed by the number of protocol deviations
Time frame: Over total study period (up to 96 weeks per participant)
Proportion of participants intolerant to the study drug who discontinue trial treatment
Time frame: Over total study period (up to 96 weeks per participant)
Proportion of participants receiving the allocated treatment at 48 weeks
Time frame: At 48 weeks
Proportion of participants receiving the allocated treatment at 96 weeks
Time frame: At 96 weeks
Proportion of participants with complete primary efficacy outcome data at 48 weeks
Time frame: At 48 weeks
Proportion of participants with complete primary efficacy outcome data at 96 weeks
Time frame: At 96 weeks
Proportion of participants lost to follow-up
Time frame: Over total study period (up to 96 weeks per participant)
Frequency of treatment-related adverse events
Incidence and severity of AEs, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Time frame: Over total study period (up to 96 weeks per participant)
Annual rate of decline in percent (%) predicted forced vital capacity (FVC) over 48 weeks
Time frame: Over 48 weeks
Annual rate of decline in percent (%) predicted forced vital capacity (FVC) over 96 weeks
Time frame: Over 96 weeks
Proportion of participants having clinically meaningful progression
Clinically meaningful progression defined by the Outcome Measures in Rheumatology (OMERACT) for connective tissue disease-associated interstitial lung diseases (CTD-ILD) (defined as a ≥10% relative decline in FVC from baseline, or a ≥5% to \<10% relative decline in FVC associated with a ≥15% relative decline in diffusion capacity \[DLCO\])
Time frame: Over total study period (up to 96 weeks per participant)
Time to clinically meaningful progression
Clinically meaningful progression as defined by Outcome Measures in Rheumatology (OMERACT) for connective tissue disease- associated interstitial lung diseases (CTD-ILD) (defined as a ≥10% relative decline in FVC from baseline, or a ≥5% to \<10% relative decline in FVC associated with a ≥15% relative decline in diffusion capacity \[DLCO\])
Time frame: Over total study period (up to 96 weeks per participant)
Proportion of participants having an absolute decrease in FVC of at least 3.3% predicted
An absolute decrease in FVC of at least 3.3% predicted was proposed as the minimal clinically important difference estimate for worsening of FVC in patients with SSc-ILD.
Time frame: Over total study period (up to 96 weeks per participant)
Time to an absolute decrease in FVC of at least 3.3% predicted
An absolute decrease in FVC of at least 3.3% predicted was proposed as the minimal clinically important difference estimate for worsening of FVC in patients with SSc-ILD.
Time frame: Over total study period (up to 96 weeks per participant)
Proportion of participants having progressive pulmonary fibrosis
Progressive pulmonary fibrosis defined by 2022 ATS/ERS/JRS/ALAT guidelines
Time frame: Over total study period (up to 96 weeks per participant)
Time to progressive pulmonary fibrosis
Progressive pulmonary fibrosis defined by 2022 ATS/ERS/JRS/ALAT guidelines
Time frame: Over total study period (up to 96 weeks per participant)
Annual rate of decline in percent (%) predicted total lung capacity over 48 weeks
Time frame: Over 48 weeks
Annual rate of decline in percent (%) predicted total lung capacity over 96 weeks
Time frame: Over 96 weeks
Annual rate of decline in percent (%) predicted diffusion capacity for carbon monoxide (DLCO) over 48 weeks
Time frame: Over 48 weeks
Annual rate of decline in percent (%) predicted DLCO over 96 weeks
Time frame: Over 96 weeks
Change from baseline in percent (%) extent of ILD, ground-glass opacities, reticular infiltrates and honeycombing, and in pulmonary vessel volume at 48 weeks
Measured on high-resolution computed tomography chest scan using automated lung texture analysis
Time frame: At 48 weeks
Change from baseline in percent (%) extent of ILD, ground-glass opacities, reticular infiltrates and honeycombing, and in pulmonary vessel volume at 96 weeks
Measured on high-resolution computed tomography chest scan using automated lung texture analysis
Time frame: At 96 weeks
Change from baseline in St-George Respiratory Questionnaire at 48 weeks
Scores range from 0 to 100, with higher scores indicating more limitations.
Time frame: At 48 weeks
Change from baseline in St-George Respiratory Questionnaire at 96 weeks
Scores range from 0 to 100, with higher scores indicating more limitations.
Time frame: At 96 weeks
Change from baseline in Leicester Cough Questionnaire at 48 weeks
Scores (total) range from 3 to 21, with higher scores indicating less limitations.
Time frame: At 48 weeks
Change from baseline in Leicester Cough Questionnaire at 96 weeks
Scores (total) range from 3 to 21, with higher scores indicating less limitations.
Time frame: At 96 weeks
Change from baseline in health assessment questionnaire modified for scleroderma at 48 weeks
The SHAQ consists of the Health assessment questionnaire (HAQ) and visual analogue scales for pain, patient global assessment, vascular, digital ulcers, lung involvement and gastrointestinal involvement. Scores range from 0 to 3, with higher scores indicating more limitations.
Time frame: At 48 weeks
Change from baseline in health assessment questionnaire modified for scleroderma at 96 weeks
The SHAQ consists of the Health assessment questionnaire (HAQ) and visual analogue scales for pain, patient global assessment, vascular, digital ulcers, lung involvement and gastrointestinal involvement. Scores range from 0 to 3, with higher scores indicating more limitations.
Time frame: At 96 weeks
Change from baseline in 36-items short form survey (SF-36) at 48 weeks
Eight scales with scores range from 0 to 100, with higher scores indicating less limitations.
Time frame: At 48 weeks
Change from baseline in 36-items short form survey (SF-36) at 96 weeks
Eight scales with scores ranging from 0 to 100, with higher scores indicating less limitations.
Time frame: At 96 weeks
Change from baseline in EuroQoL five dimensions (EQ-5D-5L) at 48 weeks
The EQ-5D-5L questionnaire possesses 5 levels for each of the five dimensions. The five dimensions are mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, with the following possible five responses: no problems, slight problems, moderate problems, severe problems, unable to/extreme problems. Scores are converted into an index value ranging from 0 to 1, with higher scores indicating better health state.
Time frame: At 48 weeks
Change from baseline in EuroQoL five dimensions (EQ-5D-5L) at 96 weeks
The EQ-5D-5L questionnaire possesses 5 levels for each of the five dimensions. The five dimensions are mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, with the following possible five responses: no problems, slight problems, moderate problems, severe problems, unable to/extreme problems. Scores are converted into an index value ranging from 0 to 1, with higher scores indicating better health state.
Time frame: At 96 weeks
Change from baseline in patient global assessment at 48 weeks
Visual analogue scale from 0 to 10, with higher scores indicating worse disease.
Time frame: At 48 weeks
Change from baseline in patient global assessment at 96 weeks
Visual analogue scale from 0 to 10, with higher scores indicating worse disease.
Time frame: At 96 weeks
Change from baseline in physician global assessment at 48 weeks
Visual analogue scale from 0 to 10, with higher scores indicating worse disease.
Time frame: At 48 weeks
Change from baseline in physician global assessment at 96 weeks
Visual analogue scale from 0 to 10, with higher scores indicating worse disease.
Time frame: At 96 weeks
Change from baseline in 6-minute walk oxygen saturation at 48 weeks
Oxygen saturation at nadir during the 6-minute walk test
Time frame: At 48 weeks
Change from baseline in 6-minute walk oxygen desaturation at 96 weeks
Oxygen saturation at nadir during the 6-minute walk test
Time frame: At 96 weeks
Change from baseline in modified Rodnan skin score (mRSS) at 48 weeks
Scores range from 0 to 51, with higher scores indicating more skin involvement.
Time frame: At 48 weeks
Change from baseline in modified Rodnan skin score (mRSS) at 96 weeks
Scores range from 0 to 51, with higher scores indicating more skin involvement.
Time frame: At 96 weeks
Change from baseline in nailfold capillary density at 48 weeks
Mean number of capillaries per mm
Time frame: At 48 weeks
Change from baseline in nailfold capillary density at 96 weeks
Mean number of capillaries per mm
Time frame: At 96 weeks
Change from baseline in nailfold capillaroscopy abnormalities and patterns at 48 weeks
Ectasias/megacapillaries are scored using a semi-quantitative scale (0 = no, 1 = ≤33%, 2= 33-66%, and 3 = ≥66% abnormalities/linear mm)
Time frame: At 48 weeks
Change from baseline in nailfold capillaroscopy abnormalities and patterns at 96 weeks
Ectasias/megacapillaries are scored using a semi-quantitative scale (0 = no, 1 = ≤33%, 2= 33-66%, and 3 = ≥66% abnormalities/linear mm)
Time frame: At 96 weeks
Change from baseline in quantitative SSc autoantibody titers at 48 weeks
Time frame: At 48 weeks
Change from baseline in quantitative SSc autoantibody titers at 96 weeks
Time frame: At 96 weeks
Change from baseline in Krebs von Lungen 6 (KL-6) titers at 48 weeks
Time frame: At 48 weeks
Change from baseline in Krebs von Lungen 6 (KL-6) titers at 96 weeks
Time frame: At 96 weeks
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Centre hospitalier de l'Université de Montréal (CHUM)