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系统性硬化症伴亚临床间质性肺病吗替麦考酚酯 (SSc-mILD)

2026年9月25日 更新者：Centre hospitalier de l'Université de Montréal (CHUM)

随机双盲安慰剂对照临床试验评估吗替麦考酚酯在与系统性硬化症相关的亚临床间质性肺病中的疗效：一项可行性研究

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.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (估计的)

35

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 加拿大
    • Quebec
      • Montreal、Quebec、加拿大、H2X 3E4
        • 招聘中
        • Centre hospitalier de l'Université de Montréal (CHUM)
        • 接触：
        • 首席研究员：
          • Sabrina Hoa, MD MSc
      • Montreal、Quebec、加拿大、H3T 1E2
        • 尚未招聘
        • Jewish General Hospital - CIUSSS-COMTL
        • 接触：
          • Marie Hudson, MD
        • 首席研究员：
          • Marie Hudson, MD
      • Québec、Quebec、加拿大
        • 尚未招聘
        • Institut Universitaire de Cardiologie et Pneumologie de Québec
        • 接触：
        • 首席研究员：
          • Geneviève Dion, MD

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：其他
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
实验性的：Mycophenolate mofetil

2 to 4 capsules of mycophenolate mofetil twice daily.
药品：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
安慰剂比较：Placebo

2 to 4 capsules of placebo twice daily.
其他：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

研究衡量的是什么？

主要结果指标

结果测量
大体时间
每个站点确定的可能符合条件的患者总数
大体时间：一年多
一年多
每个站点提供同意的潜在合格患者的比例
大体时间：一年多
一年多
每个站点符合资格标准的同意参与者的比例
大体时间：一年多
一年多
每个站点随机参与者的月率
大体时间：一年多
一年多
通过参与者剂量日记评估的治疗依从性
大体时间：从每个参与者服用的第一剂到最后一剂，最多 96 周
从每个参与者服用的第一剂到最后一剂，最多 96 周
药房责任日志评估的药物依从率
大体时间：从每个参与者服用的第一剂到最后一剂，最多 96 周
从每个参与者服用的第一剂到最后一剂，最多 96 周
根据方案偏差的数量评估对研究方案的遵守情况
大体时间：在整个学习期间（每个参与者最多 96 周）
在整个学习期间（每个参与者最多 96 周）
对研究药物不耐受而停止试验治疗的参与者比例
大体时间：在整个学习期间（每个参与者最多 96 周）
在整个学习期间（每个参与者最多 96 周）
在 48 周时接受分配治疗的参与者比例
大体时间：48周
48周
在 96 周时接受分配治疗的参与者比例
大体时间：96周时
96周时
48 周时具有完整主要疗效结果数据的参与者比例
大体时间：48周
48周
96 周时具有完整主要疗效结果数据的参与者比例
大体时间：96周时
96周时
参与者失访比例
大体时间：在整个学习期间（每个参与者最多 96 周）
在整个学习期间（每个参与者最多 96 周）

次要结果测量

结果测量
措施说明
大体时间
Frequency of treatment-related adverse events
大体时间：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)

其他结果措施

结果测量
措施说明
大体时间
48 周内预测用力肺活量 (FVC) 的年下降率 (%)
大体时间：超过 48 周
超过 48 周
96 周内预测用力肺活量 (FVC) 的年下降率 (%)
大体时间：超过 96 周
超过 96 周
48 周内预测的总肺容量年下降率 (%)
大体时间：超过 48 周
超过 48 周
96 周内预测的总肺容量年下降率 (%)
大体时间：超过 96 周
超过 96 周
48 周内一氧化碳 (DLCO) 的预测扩散能力年下降率 (%)
大体时间：超过 48 周
超过 48 周
96 周内预测 DLCO 的年度下降百分比 (%)
大体时间：超过 96 周
超过 96 周
48 周时定量 SSc 自身抗体滴度相对于基线的变化
大体时间：48周
48周
96 周时定量 SSc 自身抗体滴度相对于基线的变化
大体时间：96周时
96周时
48 周时 Krebs von Lungen 6 (KL-6) 滴度相对于基线的变化
大体时间：48周
48周
96 周时 Krebs von Lungen 6 (KL-6) 滴度相对于基线的变化
大体时间：96周时
96周时
Proportion of participants having clinically meaningful progression
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：At 48 weeks

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

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

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Centre hospitalier de l'Université de Montréal (CHUM)

合作者

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

调查人员

  • 首席研究员：Sabrina Hoa, MD、Centre hospitalier de l'Université de Montréal (CHUM)

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2024年8月29日

初级完成 (估计的)

2026年12月1日

研究完成 (估计的)

2028年12月1日

研究注册日期

首次提交

2023年2月7日

首先提交符合 QC 标准的

2023年3月14日

首次发布 (实际的)

2023年3月27日

研究记录更新

最后更新发布 (实际的)

2026年9月29日

上次提交的符合 QC 标准的更新

2026年9月25日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • MP-02-2023-11180

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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