Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon for en kildetekst.

Mykofenolatmofetil ved systemisk sklerose med subklinisk interstitiell lungesykdom (SSc-mILD)

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

Randomisert dobbeltblind placebokontrollert klinisk studie for å vurdere effekten av mykofenolatmofetil ved subklinisk interstitiell lungesykdom assosiert med systemisk sklerose: en mulighetsstudie

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.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert 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.

Studietype

Intervensjonell

Registrering (Antatt)

35

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H2X 3E4
        • Rekruttering
        • Centre hospitalier de l'Université de Montréal (CHUM)
        • Ta kontakt med:
        • Hovedetterforsker:
          • Sabrina Hoa, MD MSc
      • Montreal, Quebec, Canada, H3T 1E2
        • Har ikke rekruttert ennå
        • Jewish General Hospital - CIUSSS-COMTL
        • Ta kontakt med:
          • Marie Hudson, MD
        • Hovedetterforsker:
          • Marie Hudson, MD
      • Québec, Quebec, Canada
        • Har ikke rekruttert ennå
        • Institut Universitaire de Cardiologie et Pneumologie de Québec
        • Ta kontakt med:
        • Hovedetterforsker:
          • Geneviève Dion, MD

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Annen
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Mycophenolate mofetil

2 to 4 capsules of mycophenolate mofetil twice daily.
Legemiddel: 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.
Annen: 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

Hva måler studien?

Primære resultatmål

Resultatmål
Tidsramme
Totalt antall potensielt kvalifiserte pasienter identifisert per sted
Tidsramme: Over ett år
Over ett år
Andel potensielt kvalifiserte pasienter som gir samtykke per nettsted
Tidsramme: Over ett år
Over ett år
Andel samtykkede deltakere som oppfyller kvalifikasjonskriteriene per nettsted
Tidsramme: Over ett år
Over ett år
Månedlig rate av randomiserte deltakere per nettsted
Tidsramme: Over ett år
Over ett år
Overholdelse av behandling som vurdert av deltakerdoseringsdagbøker
Tidsramme: Fra den første dosen til den siste dosen tatt for hver deltaker, opptil 96 uker
Fra den første dosen til den siste dosen tatt for hver deltaker, opptil 96 uker
Medikamentoverholdelsesgrad som vurderes av Pharmacy Accountability Logs
Tidsramme: Fra den første dosen til den siste dosen tatt for hver deltaker, opptil 96 uker
Fra den første dosen til den siste dosen tatt for hver deltaker, opptil 96 uker
Overholdelse av studieprotokollen vurdert ut fra antall protokollavvik
Tidsramme: Over total studieperiode (opptil 96 uker per deltaker)
Over total studieperiode (opptil 96 uker per deltaker)
Andel deltakere som er intolerante overfor studiemedisinen som avbryter prøvebehandling
Tidsramme: Over total studieperiode (opptil 96 uker per deltaker)
Over total studieperiode (opptil 96 uker per deltaker)
Andel deltakere som mottar tildelt behandling ved 48 uker
Tidsramme: Ved 48 uker
Ved 48 uker
Andel deltakere som mottar tildelt behandling ved 96 uker
Tidsramme: Ved 96 uker
Ved 96 uker
Andel deltakere med komplette primære effektutfallsdata etter 48 uker
Tidsramme: Ved 48 uker
Ved 48 uker
Andel deltakere med fullstendige primære effektutfallsdata etter 96 uker
Tidsramme: Ved 96 uker
Ved 96 uker
Andel deltakere tapte for oppfølging
Tidsramme: Over total studieperiode (opptil 96 uker per deltaker)
Over total studieperiode (opptil 96 uker per deltaker)

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
Tidsramme
Årlig nedgang i prosent (%) spådd tvungen vitalkapasitet (FVC) over 48 uker
Tidsramme: Over 48 uker
Over 48 uker
Årlig nedgang i prosent (%) spådd tvungen vitalkapasitet (FVC) over 96 uker
Tidsramme: Over 96 uker
Over 96 uker
Årlig nedgang i prosent (%) spådde total lungekapasitet over 48 uker
Tidsramme: Over 48 uker
Over 48 uker
Årlig nedgang i prosent (%) spådde total lungekapasitet over 96 uker
Tidsramme: Over 96 uker
Over 96 uker
Årlig nedgang i prosent (%) spådd diffusjonskapasitet for karbonmonoksid (DLCO) over 48 uker
Tidsramme: Over 48 uker
Over 48 uker
Årlig nedgang i prosent (%) spådde DLCO over 96 uker
Tidsramme: Over 96 uker
Over 96 uker
Endring fra baseline i kvantitative SSc-autoantistofftitere ved 48 uker
Tidsramme: Ved 48 uker
Ved 48 uker
Endring fra baseline i kvantitative SSc-autoantistofftitere ved 96 uker
Tidsramme: Ved 96 uker
Ved 96 uker
Endring fra baseline i Krebs von Lungen 6 (KL-6) titere ved 48 uker
Tidsramme: Ved 48 uker
Ved 48 uker
Endring fra baseline i Krebs von Lungen 6 (KL-6) titere ved 96 uker
Tidsramme: Ved 96 uker
Ved 96 uker
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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Samarbeidspartnere

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

Etterforskere

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

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

29. august 2024

Primær fullføring (Antatt)

1. desember 2026

Studiet fullført (Antatt)

1. desember 2028

Datoer for studieregistrering

Først innsendt

7. februar 2023

Først innsendt som oppfylte QC-kriteriene

14. mars 2023

Først lagt ut (Faktiske)

27. mars 2023

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

29. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

25. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • MP-02-2023-11180

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere