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Mykofenolatmofetil vid systemisk skleros med subklinisk interstitiell lungsjukdom (SSc-mILD)

25 september 2026 uppdaterad av: Centre hospitalier de l'Université de Montréal (CHUM)

Randomiserad dubbelblind placebokontrollerad klinisk prövning för att bedöma effekten av mykofenolatmofetil vid subklinisk interstitiell lungsjukdom associerad med systemisk skleros: en genomförbarhetsstudie

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.

Studieöversikt

Status

Rekrytering

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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:

  1. Determine the rate of patient recruitment at three centers over one year, and identify barriers and solutions to recruitment;
  2. Determine the proportion of participants receiving the allocated treatment and with complete primary efficacy outcome data at 48 and 96 weeks; and
  3. Generate preliminary data on clinical efficacy outcomes that will contribute information to the analysis of the phase III trial through a Bayesian inference framework.

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.

Studietyp

Interventionell

Inskrivning (Beräknad)

35

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studiekontakt

Studera Kontakt Backup

Studieorter

  • Kanada
    • Quebec
      • Montreal, Quebec, Kanada, H2X 3E4
        • Rekrytering
        • Centre hospitalier de l'Université de Montréal (CHUM)
        • Kontakt:
        • Huvudutredare:
          • Sabrina Hoa, MD MSc
      • Montreal, Quebec, Kanada, H3T 1E2
        • Har inte rekryterat ännu
        • Jewish General Hospital - CIUSSS-COMTL
        • Kontakt:
          • Marie Hudson, MD
        • Huvudutredare:
          • Marie Hudson, MD
      • Québec, Quebec, Kanada
        • Har inte rekryterat ännu
        • Institut Universitaire de Cardiologie et Pneumologie de Québec
        • Kontakt:
        • Huvudutredare:
          • Geneviève Dion, MD

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  1. Able and willing to provide informed consent and adhere to study protocol;
  2. Women and men of all race/ethnicity, aged 18 years and older;
  3. SSc based on 2013 ACR-EULAR classification criteria;
  4. Presence of interstitial lung disease on HRCT scan, obtained within 12 months before screening, that shows fibrosis affecting less than 20% of the lungs, as confirmed by an expert radiologist;
  5. Diagnosis of ILD within 7 years before screening;
  6. Forced vital capacity of 80% predicted and above, on pulmonary function tests obtained within 6 months before screening;
  7. Able to communicate in French or English;

Exclusion Criteria:

  1. Progressive pulmonary fibrosis, defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation, as defined by the 2022 ATS/ERS/JRS/ALAT Clinical Practice Guideline;

  2. Use of medications with putative lung disease-modifying properties:

    1. Current use of MMF, mycophenolic acid, azathioprine, calcineurin inhibitors (e.g. tacrolimus, cyclosporin A), tocilizumab, nintedanib, pirfenidone or corticosteroids (Prednisone equivalent dose >10 mg/day) at time of screening
    2. Cyclophosphamide within one year prior to screening
    3. Rituximab within 6 months prior to screening
    4. Cell therapies (including stem cell transplantation) within one year prior to screening

  3. Current use of other biological, targeted synthetic or investigational products with immunosuppressive effects (e.g. TNF inhibitors, abatacept, tofacitinib) at time of screening

  4. Any contraindication to MMF, including:

    1. Pregnancy and/or breastfeeding
    2. Female of childbearing potential not using reliable method of contraception
    3. Persistent leucopenia (white blood cell count <3.0 x103/μL)
    4. Persistent thrombocytopenia (platelet count <100 x103/μL)
    5. Persistent anemia (hemoglobin <100 g/L)
    6. Baseline liver enzymes (alanine transaminase (ALT) or aspartate transaminase (AST)) or bilirubin >1.5 times the upper limit of normal, other than due to Gilbert's disease
    7. Uncontrolled congestive heart failure
    8. Active infection (lung or elsewhere)
    9. Active solid or hematological malignancy (other than basal cell cancer of the skin or cervical carcinoma in situ removed entirely by biopsy)
    10. Active peptic ulcer disease
    11. Other serious concomitant medical illness, unreliability or drug abuse that might compromise the patient's ability to safely take MMF
    12. Use of drugs or products with significant interactions with MMF

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Övrig
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Mycophenolate mofetil

2 to 4 capsules of mycophenolate mofetil twice daily.
Läkemedel: Mycophenolate Mofetil

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
Placebo-jämförare: Placebo

2 to 4 capsules of placebo twice daily.
Övrig: Placebo

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

Vad mäter studien?

Primära resultatmått

Resultatmått
Tidsram
Totalt antal potentiellt kvalificerade patienter identifierade per plats
Tidsram: Över ett år
Över ett år
Andel potentiellt kvalificerade patienter som ger samtycke per plats
Tidsram: Över ett år
Över ett år
Andel godkända deltagare som uppfyller behörighetskriterierna per webbplats
Tidsram: Över ett år
Över ett år
Månatlig andel randomiserade deltagare per webbplats
Tidsram: Över ett år
Över ett år
Följsamhet till behandling som bedömts av deltagares doseringsdagböcker
Tidsram: Från den första dosen till den sista dosen som tas för varje deltagare, upp till 96 veckor
Från den första dosen till den sista dosen som tas för varje deltagare, upp till 96 veckor
Läkemedelsefterlevnadsgrad bedömd av apotekens ansvarsloggar
Tidsram: Från den första dosen till den sista dosen som tas för varje deltagare, upp till 96 veckor
Från den första dosen till den sista dosen som tas för varje deltagare, upp till 96 veckor
Efterlevnad av studieprotokollet bedömt utifrån antalet protokollavvikelser
Tidsram: Över den totala studieperioden (upp till 96 veckor per deltagare)
Över den totala studieperioden (upp till 96 veckor per deltagare)
Andel deltagare som är intoleranta mot studieläkemedlet som avbryter försöksbehandling
Tidsram: Över den totala studieperioden (upp till 96 veckor per deltagare)
Över den totala studieperioden (upp till 96 veckor per deltagare)
Andel deltagare som får den tilldelade behandlingen vid 48 veckor
Tidsram: Vid 48 veckor
Vid 48 veckor
Andel deltagare som får den tilldelade behandlingen vid 96 veckor
Tidsram: Vid 96 veckor
Vid 96 veckor
Andel deltagare med fullständiga primära effektdata efter 48 veckor
Tidsram: Vid 48 veckor
Vid 48 veckor
Andel deltagare med fullständiga primära effektdata vid 96 veckor
Tidsram: Vid 96 veckor
Vid 96 veckor
Andel deltagare förlorade till uppföljning
Tidsram: Över den totala studieperioden (upp till 96 veckor per deltagare)
Över den totala studieperioden (upp till 96 veckor per deltagare)

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Frequency of treatment-related adverse events
Tidsram: Over total study period (up to 96 weeks per participant)

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)
Over total study period (up to 96 weeks per participant)

Andra resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Årlig nedgångstakt i procent (%) förutspådd forcerad vitalkapacitet (FVC) under 48 veckor
Tidsram: Över 48 veckor
Över 48 veckor
Årlig nedgångstakt i procent (%) förutspådd forcerad vitalkapacitet (FVC) under 96 veckor
Tidsram: Över 96 veckor
Över 96 veckor
Årlig minskningstakt i procent (%) förutspådde total lungkapacitet under 48 veckor
Tidsram: Över 48 veckor
Över 48 veckor
Årlig minskningstakt i procent (%) förutspådde total lungkapacitet under 96 veckor
Tidsram: Över 96 veckor
Över 96 veckor
Årlig minskningstakt i procent (%) förutspådd diffusionskapacitet för kolmonoxid (DLCO) under 48 veckor
Tidsram: Över 48 veckor
Över 48 veckor
Årlig nedgångstakt i procent (%) förutspådde DLCO under 96 veckor
Tidsram: Över 96 veckor
Över 96 veckor
Ändring från baslinjen i kvantitativa SSc-autoantikroppstitrar vid 48 veckor
Tidsram: Vid 48 veckor
Vid 48 veckor
Ändring från baslinjen i kvantitativa SSc-autoantikroppstitrar vid 96 veckor
Tidsram: Vid 96 veckor
Vid 96 veckor
Förändring från baslinjen i Krebs von Lungen 6 (KL-6) titrar vid 48 veckor
Tidsram: Vid 48 veckor
Vid 48 veckor
Förändring från baslinjen i Krebs von Lungen 6 (KL-6) titrar vid 96 veckor
Tidsram: Vid 96 veckor
Vid 96 veckor
Proportion of participants having clinically meaningful progression
Tidsram: Over total study period (up to 96 weeks per participant)

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])
Over total study period (up to 96 weeks per participant)
Time to clinically meaningful progression
Tidsram: Over total study period (up to 96 weeks per participant)

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])
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
Tidsram: Over total study period (up to 96 weeks per participant)

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.
Over total study period (up to 96 weeks per participant)
Time to an absolute decrease in FVC of at least 3.3% predicted
Tidsram: Over total study period (up to 96 weeks per participant)

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.
Over total study period (up to 96 weeks per participant)
Proportion of participants having progressive pulmonary fibrosis
Tidsram: Over total study period (up to 96 weeks per participant)

Progressive pulmonary fibrosis defined by 2022 ATS/ERS/JRS/ALAT guidelines
Over total study period (up to 96 weeks per participant)
Time to progressive pulmonary fibrosis
Tidsram: Over total study period (up to 96 weeks per participant)

Progressive pulmonary fibrosis defined by 2022 ATS/ERS/JRS/ALAT guidelines
Over total study period (up to 96 weeks per participant)
Change from baseline in percent (%) extent of ILD, ground-glass opacities, reticular infiltrates and honeycombing, and in pulmonary vessel volume at 48 weeks
Tidsram: At 48 weeks

Measured on high-resolution computed tomography chest scan using automated lung texture analysis
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
Tidsram: At 96 weeks

Measured on high-resolution computed tomography chest scan using automated lung texture analysis
At 96 weeks
Change from baseline in St-George Respiratory Questionnaire at 48 weeks
Tidsram: At 48 weeks

Scores range from 0 to 100, with higher scores indicating more limitations.
At 48 weeks
Change from baseline in St-George Respiratory Questionnaire at 96 weeks
Tidsram: At 96 weeks

Scores range from 0 to 100, with higher scores indicating more limitations.
At 96 weeks
Change from baseline in Leicester Cough Questionnaire at 48 weeks
Tidsram: At 48 weeks

Scores (total) range from 3 to 21, with higher scores indicating less limitations.
At 48 weeks
Change from baseline in Leicester Cough Questionnaire at 96 weeks
Tidsram: At 96 weeks

Scores (total) range from 3 to 21, with higher scores indicating less limitations.
At 96 weeks
Change from baseline in health assessment questionnaire modified for scleroderma at 48 weeks
Tidsram: 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.
At 48 weeks
Change from baseline in health assessment questionnaire modified for scleroderma at 96 weeks
Tidsram: 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.
At 96 weeks
Change from baseline in 36-items short form survey (SF-36) at 48 weeks
Tidsram: At 48 weeks

Eight scales with scores range from 0 to 100, with higher scores indicating less limitations.
At 48 weeks
Change from baseline in 36-items short form survey (SF-36) at 96 weeks
Tidsram: At 96 weeks

Eight scales with scores ranging from 0 to 100, with higher scores indicating less limitations.
At 96 weeks
Change from baseline in EuroQoL five dimensions (EQ-5D-5L) at 48 weeks
Tidsram: 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.
At 48 weeks
Change from baseline in EuroQoL five dimensions (EQ-5D-5L) at 96 weeks
Tidsram: 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.
At 96 weeks
Change from baseline in patient global assessment at 48 weeks
Tidsram: At 48 weeks

Visual analogue scale from 0 to 10, with higher scores indicating worse disease.
At 48 weeks
Change from baseline in patient global assessment at 96 weeks
Tidsram: At 96 weeks

Visual analogue scale from 0 to 10, with higher scores indicating worse disease.
At 96 weeks
Change from baseline in physician global assessment at 48 weeks
Tidsram: At 48 weeks

Visual analogue scale from 0 to 10, with higher scores indicating worse disease.
At 48 weeks
Change from baseline in physician global assessment at 96 weeks
Tidsram: At 96 weeks

Visual analogue scale from 0 to 10, with higher scores indicating worse disease.
At 96 weeks
Change from baseline in 6-minute walk oxygen saturation at 48 weeks
Tidsram: At 48 weeks

Oxygen saturation at nadir during the 6-minute walk test
At 48 weeks
Change from baseline in 6-minute walk oxygen desaturation at 96 weeks
Tidsram: At 96 weeks

Oxygen saturation at nadir during the 6-minute walk test
At 96 weeks
Change from baseline in modified Rodnan skin score (mRSS) at 48 weeks
Tidsram: At 48 weeks

Scores range from 0 to 51, with higher scores indicating more skin involvement.
At 48 weeks
Change from baseline in modified Rodnan skin score (mRSS) at 96 weeks
Tidsram: At 96 weeks

Scores range from 0 to 51, with higher scores indicating more skin involvement.
At 96 weeks
Change from baseline in nailfold capillary density at 48 weeks
Tidsram: At 48 weeks

Mean number of capillaries per mm
At 48 weeks
Change from baseline in nailfold capillary density at 96 weeks
Tidsram: At 96 weeks

Mean number of capillaries per mm
At 96 weeks
Change from baseline in nailfold capillaroscopy abnormalities and patterns at 48 weeks
Tidsram: 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)
At 48 weeks
Change from baseline in nailfold capillaroscopy abnormalities and patterns at 96 weeks
Tidsram: 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)
At 96 weeks

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Samarbetspartners

McGill University
Canadian Institutes of Health Research (CIHR)
University of Calgary
Jewish General Hospital
Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
Sclérodermie Québec

Utredare

  • Huvudutredare: Sabrina Hoa, MD, Centre hospitalier de l'Université de Montréal (CHUM)

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

29 augusti 2024

Primärt slutförande (Beräknad)

1 december 2026

Avslutad studie (Beräknad)

1 december 2028

Studieregistreringsdatum

Först inskickad

7 februari 2023

Först inskickad som uppfyllde QC-kriterierna

14 mars 2023

Första postat (Faktisk)

27 mars 2023

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

29 september 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

25 september 2026

Senast verifierad

1 september 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • MP-02-2023-11180

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