Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

Micofenolato de mofetil na esclerose sistêmica com doença pulmonar intersticial subclínica (SSc-mILD)

25 de setembro de 2026 atualizado por: Centre hospitalier de l'Université de Montréal (CHUM)

Ensaio clínico randomizado duplo-cego controlado por placebo para avaliar a eficácia do micofenolato de mofetil na doença pulmonar intersticial subclínica associada à esclerose sistêmica: um estudo de viabilidade

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.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Estimado)

35

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Locais de estudo

  • Canadá
    • Quebec
      • Montreal, Quebec, Canadá, H2X 3E4
        • Recrutamento
        • Centre hospitalier de l'Université de Montréal (CHUM)
        • Contato:
        • Investigador principal:
          • Sabrina Hoa, MD MSc
      • Montreal, Quebec, Canadá, H3T 1E2
        • Ainda não está recrutando
        • Jewish General Hospital - CIUSSS-COMTL
        • Contato:
          • Marie Hudson, MD
        • Investigador principal:
          • Marie Hudson, MD
      • Québec, Quebec, Canadá
        • Ainda não está recrutando
        • Institut Universitaire de Cardiologie et Pneumologie de Québec
        • Contato:
        • Investigador principal:
          • Geneviève Dion, MD

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Outro
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Mycophenolate mofetil

2 to 4 capsules of mycophenolate mofetil twice daily.
Medicamento: 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
Comparador de Placebo: Placebo

2 to 4 capsules of placebo twice daily.
Outro: 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

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Prazo
Número total de pacientes potencialmente elegíveis identificados por local
Prazo: Mais de um ano
Mais de um ano
Proporção de pacientes potencialmente elegíveis que fornecem consentimento por centro
Prazo: Mais de um ano
Mais de um ano
Proporção de participantes consentidos que atendem aos critérios de elegibilidade por local
Prazo: Mais de um ano
Mais de um ano
Taxa mensal de participantes randomizados por local
Prazo: Mais de um ano
Mais de um ano
Adesão ao tratamento conforme avaliado pelos Diários de Dosagem do Participante
Prazo: Desde a primeira dose até a última dose tomada para cada participante, até 96 semanas
Desde a primeira dose até a última dose tomada para cada participante, até 96 semanas
Taxa de adesão ao medicamento conforme avaliada pelos Registros de Responsabilidade Farmacêutica
Prazo: Desde a primeira dose até a última dose tomada para cada participante, até 96 semanas
Desde a primeira dose até a última dose tomada para cada participante, até 96 semanas
Aderência ao protocolo do estudo avaliada pelo número de desvios de protocolo
Prazo: Durante o período total do estudo (até 96 semanas por participante)
Durante o período total do estudo (até 96 semanas por participante)
Proporção de participantes intolerantes ao medicamento do estudo que descontinuaram o tratamento experimental
Prazo: Durante o período total do estudo (até 96 semanas por participante)
Durante o período total do estudo (até 96 semanas por participante)
Proporção de participantes que receberam o tratamento alocado em 48 semanas
Prazo: Com 48 semanas
Com 48 semanas
Proporção de participantes que receberam o tratamento alocado em 96 semanas
Prazo: Com 96 semanas
Com 96 semanas
Proporção de participantes com dados completos de resultados primários de eficácia em 48 semanas
Prazo: Com 48 semanas
Com 48 semanas
Proporção de participantes com dados completos de resultados primários de eficácia em 96 semanas
Prazo: Com 96 semanas
Com 96 semanas
Proporção de participantes perdidos para acompanhamento
Prazo: Durante o período total do estudo (até 96 semanas por participante)
Durante o período total do estudo (até 96 semanas por participante)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Frequency of treatment-related adverse events
Prazo: 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)

Outras medidas de resultado

Medida de resultado
Descrição da medida
Prazo
Taxa anual de declínio em porcentagem (%) da capacidade vital forçada prevista (CVF) durante 48 semanas
Prazo: Mais de 48 semanas
Mais de 48 semanas
Taxa anual de declínio em porcentagem (%) da capacidade vital forçada prevista (FVC) em 96 semanas
Prazo: Mais de 96 semanas
Mais de 96 semanas
Taxa anual de declínio em porcentagem (%) da capacidade pulmonar total prevista em 48 semanas
Prazo: Mais de 48 semanas
Mais de 48 semanas
Taxa anual de declínio em porcentagem (%) da capacidade pulmonar total prevista em 96 semanas
Prazo: Mais de 96 semanas
Mais de 96 semanas
Taxa anual de declínio em porcentagem (%) da capacidade de difusão prevista para monóxido de carbono (DLCO) ao longo de 48 semanas
Prazo: Mais de 48 semanas
Mais de 48 semanas
Taxa anual de declínio em percentual (%) DLCO previsto ao longo de 96 semanas
Prazo: Mais de 96 semanas
Mais de 96 semanas
Alteração da linha de base nos títulos quantitativos de autoanticorpos para ES em 48 semanas
Prazo: Com 48 semanas
Com 48 semanas
Alteração da linha de base nos títulos quantitativos de autoanticorpos para ES em 96 semanas
Prazo: Com 96 semanas
Com 96 semanas
Mudança da linha de base em títulos de Krebs von Lungen 6 (KL-6) em 48 semanas
Prazo: Com 48 semanas
Com 48 semanas
Mudança da linha de base em títulos de Krebs von Lungen 6 (KL-6) em 96 semanas
Prazo: Com 96 semanas
Com 96 semanas
Proportion of participants having clinically meaningful progression
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: At 48 weeks

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

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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Centre hospitalier de l'Université de Montréal (CHUM)

Colaboradores

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

Investigadores

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

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

29 de agosto de 2024

Conclusão Primária (Estimado)

1 de dezembro de 2026

Conclusão do estudo (Estimado)

1 de dezembro de 2028

Datas de inscrição no estudo

Enviado pela primeira vez

7 de fevereiro de 2023

Enviado pela primeira vez que atendeu aos critérios de CQ

14 de março de 2023

Primeira postagem (Real)

27 de março de 2023

Atualizações de registro de estudo

Última Atualização Postada (Real)

29 de setembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

25 de setembro de 2026

Última verificação

1 de setembro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • MP-02-2023-11180

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

produto fabricado e exportado dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Se inscrever