Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

Mycophenolatmofetil i systemisk sklerose med subklinisk interstitiel lungesygdom (SSc-mILD)

25. september 2026 opdateret af: Centre hospitalier de l'Université de Montréal (CHUM)

Randomiseret dobbeltblindet placebokontrolleret klinisk forsøg for at vurdere effektiviteten af ​​mycophenolatmofetil ved subklinisk interstitiel lungesygdom associeret med systemisk sklerose: en gennemførlighedsundersøgelse

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.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

35

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Undersøgelse Kontakt Backup

Studiesteder

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H2X 3E4
        • Rekruttering
        • Centre hospitalier de l'Université de Montréal (CHUM)
        • Kontakt:
        • Ledende efterforsker:
          • Sabrina Hoa, MD MSc
      • Montreal, Quebec, Canada, H3T 1E2
        • Ikke rekrutterer endnu
        • Jewish General Hospital - CIUSSS-COMTL
        • Kontakt:
          • Marie Hudson, MD
        • Ledende efterforsker:
          • Marie Hudson, MD
      • Québec, Quebec, Canada
        • Ikke rekrutterer endnu
        • Institut Universitaire de Cardiologie et Pneumologie de Québec
        • Kontakt:
        • Ledende efterforsker:
          • Geneviève Dion, MD

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Andet
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Mycophenolate mofetil

2 to 4 capsules of mycophenolate mofetil twice daily.
Medicin: 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 komparator: Placebo

2 to 4 capsules of placebo twice daily.
Andet: 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

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Samlet antal potentielt kvalificerede patienter identificeret pr. sted
Tidsramme: Over et år
Over et år
Andel af potentielt kvalificerede patienter, der giver samtykke pr. websted
Tidsramme: Over et år
Over et år
Andel af samtykkede deltagere, der opfylder berettigelseskriterierne pr. websted
Tidsramme: Over et år
Over et år
Månedlig rate af randomiserede deltagere pr. websted
Tidsramme: Over et år
Over et år
Overholdelse af behandling som vurderet af deltagerdoseringsdagbøger
Tidsramme: Fra den første dosis til den sidste dosis, der tages for hver deltager, op til 96 uger
Fra den første dosis til den sidste dosis, der tages for hver deltager, op til 96 uger
Lægemiddeloverholdelsesrate som vurderet af Pharmacy Accountability Logs
Tidsramme: Fra den første dosis til den sidste dosis, der tages for hver deltager, op til 96 uger
Fra den første dosis til den sidste dosis, der tages for hver deltager, op til 96 uger
Overholdelse af undersøgelsesprotokollen vurderet ud fra antallet af protokolafvigelser
Tidsramme: Over den samlede undersøgelsesperiode (op til 96 uger pr. deltager)
Over den samlede undersøgelsesperiode (op til 96 uger pr. deltager)
Andel af deltagere, der er intolerante over for undersøgelseslægemidlet, som ophører med forsøgsbehandling
Tidsramme: Over den samlede undersøgelsesperiode (op til 96 uger pr. deltager)
Over den samlede undersøgelsesperiode (op til 96 uger pr. deltager)
Andel af deltagere, der modtager den tildelte behandling efter 48 uger
Tidsramme: Ved 48 uger
Ved 48 uger
Andel af deltagere, der modtager den tildelte behandling efter 96 uger
Tidsramme: 96 uger
96 uger
Andel af deltagere med komplette primære effektudfaldsdata efter 48 uger
Tidsramme: Ved 48 uger
Ved 48 uger
Andel af deltagere med fuldstændige primære effektdata efter 96 uger
Tidsramme: 96 uger
96 uger
Andel af deltagere tabt til opfølgning
Tidsramme: Over den samlede undersøgelsesperiode (op til 96 uger pr. deltager)
Over den samlede undersøgelsesperiode (op til 96 uger pr. deltager)

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Frequency of treatment-related adverse events
Tidsramme: 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)

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Årlig fald i procent (%) forudsagt forceret vitalkapacitet (FVC) over 48 uger
Tidsramme: Over 48 uger
Over 48 uger
Årlig fald i procent (%) forudsagt forceret vitalkapacitet (FVC) over 96 uger
Tidsramme: Over 96 uger
Over 96 uger
Årlig fald i procent (%) forudsagde den samlede lungekapacitet over 48 uger
Tidsramme: Over 48 uger
Over 48 uger
Årlig fald i procent (%) forudsagde den samlede lungekapacitet over 96 uger
Tidsramme: Over 96 uger
Over 96 uger
Årlig fald i procent (%) forudsagt diffusionskapacitet for carbonmonoxid (DLCO) over 48 uger
Tidsramme: Over 48 uger
Over 48 uger
Årlig fald i procent (%) forudsagde DLCO over 96 uger
Tidsramme: Over 96 uger
Over 96 uger
Ændring fra baseline i kvantitative SSc-autoantistoftitre efter 48 uger
Tidsramme: Ved 48 uger
Ved 48 uger
Ændring fra baseline i kvantitative SSc-autoantistoftitre ved 96 uger
Tidsramme: 96 uger
96 uger
Ændring fra baseline i Krebs von Lungen 6 (KL-6) titere efter 48 uger
Tidsramme: Ved 48 uger
Ved 48 uger
Ændring fra baseline i Krebs von Lungen 6 (KL-6) titere ved 96 uger
Tidsramme: 96 uger
96 uger
Proportion of participants having clinically meaningful progression
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: At 48 weeks

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

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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Samarbejdspartnere

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

Efterforskere

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

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

29. august 2024

Primær færdiggørelse (Anslået)

1. december 2026

Studieafslutning (Anslået)

1. december 2028

Datoer for studieregistrering

Først indsendt

7. februar 2023

Først indsendt, der opfyldte QC-kriterier

14. marts 2023

Først opslået (Faktiske)

27. marts 2023

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

29. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

25. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • MP-02-2023-11180

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

produkt fremstillet i og eksporteret fra U.S.A.

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Abonner