A Double Blind, Randomised, Placebo-controlled Trial Evaluating the Efficacy and Safety of Nerandomilast Over at Least 26 Weeks in Patients With Systemic Autoimmune Rheumatic Diseases Associated Interstitial Lung Diseases (SARD-ILD)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 275
- 主要终点
- Absolute change from baseline in quantitative interstitial lung disease (QILD) score [%] on high-resolution computed tomography (HRCT) at Week 26
研究概览
简要总结
Adults 18 years of age and older or above legal age with lung fibrosis related to systemic autoimmune rheumatic disease can participate in this study. People can only take part if they show no improvement in lung function after standard treatment with immunosuppressant medicine. The main purpose of this study is to find out how a medicine called nerandomilast affects the lungs in people with systemic autoimmune rheumatic disease.
Participants are put into 2 groups randomly, which means by chance. One group takes nerandomilast tablets and the other group takes placebo tablets. Placebo tablets look like nerandomilast tablets but do not contain any medicine. Participants take a tablet 2 times a day for at least 26 weeks and up to 1 year. Participants continue immunosuppressant treatment for their underlying rheumatic disease.
Participants are in the study for about 7.5 to 13 months depending on when they join the study. During this time, they visit the study site about 9 to 10 times. At study visits, participants have lung function tests. At select visits, chest imaging is performed. Participants fill in questionnaires about their symptoms and quality of life. The results between the 2 groups are compared to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has systemic autoimmune rheumatic diseases associated interstitial lung diseases (SARD-ILD), defined as
- •Diagnosis by a rheumatologist (or equally qualified medical physician) with at least 1 of the following SARDs: Rheumatoid arthritis (RA), systemic sclerosis (SSc) (participants must be anticentromere auto-antibody negative), idiopathic inflammatory myopathy (IIM), Sjögren's disease, or mixed connective tissue disease (MCTD) (participants must be anti-U1-ribonucleoprotein particle (RNP) auto-antibody positive)
- •Presence of fibrotic interstitial lung disease (ILD) on high-resolution computed tomography (HRCT), defined as presence of reticular abnormality with traction bronchiectasis with or without honeycombing (HC), with disease extent >10% on HRCT performed within 12 months of Visit 1 or, if historical scan is not available, on baseline HRCT taken prior to Visit 2, as confirmed by central review
- •No lung function improvement and no clinically significant ILD improvement as a treatment response to immunosuppressant (IS) therapy according to both criteria:
- •No improvement in absolute forced vital capacity (FVC) % predicted >5% within the 15 months prior to Visit 1, as measured by 2 spirometry assessments that must be ≥3 months apart. (Note: 1: In the case of multiple PFTs over the 15 months prior to screening, exceptional values of absolute change in FVC % predicted >5% are acceptable if the overall trend of FVC % predicted is declining or stable; note 2: Visit 1 spirometry may be used to fulfill the inclusion criterion if there is only 1 spirometry reading in the 15 months prior to Visit 1)
- •No clinically significant improvement in ILD based on clinician's judgement (including symptoms, imaging/HRCT, or other assessments as considered relevant and documented by the Investigator)
- •FVC ≥45% of predicted normal at Visit 1
- •Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥25% of predicted normal corrected for haemoglobin (Hb) within 3 months prior to or at Visit 1
- •Participants must be on stable treatment with any IS agent for ≥6 months (or ≥3 months for participants with IIM-ILD) prior to visit 2, with the following specifications:
- •If using prednisone, participants must be on stable dose for ≥4 weeks prior to Visit 2
- •If using rituximab, participants must have completed their first cycle >6 months prior to Visit 2
- •If using nintedanib, participants must be on a stable dose for ≥12 weeks prior to Visit 2
- •In the opinion of the Investigator, no change in background standard of care (SoC) treatment with immunosuppressant (IS), immunomodulator (IM), or nintedanib is planned
- •Further inclusion criteria apply
排除标准
- •Organising pneumonia as predominant pattern in the HRCT
- •Prebronchodilator forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC) <0.7 at Visit 1
- •Acute ILD exacerbation within 3 months prior to Visit 1 and/or during the screening period, based on Investigator judgement
- •Active vasculitis, unstable or uncontrolled within 8 weeks prior to Visit 1 or during the screening period
- •Any suicidal behaviour in the past 2 years
- •Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) in the past 3 months or at Visit 1, and/or at Visit 2
- •Use of any of the following medications: cyclophosphamide within 6 months of Visit 1, pirfenidone within 8 weeks of Visit 1
- •Further exclusion criteria apply
研究组 & 干预措施
Placebo
Participants with SARD-ILDs will receive placebo.
干预措施: Placebo matching nerandomilast (Drug)
Nerandomilast
Participants with SARD-ILDs will receive nerandomilast.
干预措施: Nerandomilast (Drug)
结局指标
主要结局
Absolute change from baseline in quantitative interstitial lung disease (QILD) score [%] on high-resolution computed tomography (HRCT) at Week 26
时间窗: At baseline and at Week 26
QILD will be assessed via quantitative high-resolution computed tomography (qHRCT). QILD are quantitative measures of different radiological patterns associated with lung fibrosis. QLF is a measure of reticulation with architectural distortion. QGGO is a measure of ground glass opacities (i.e. hazy or cloudy areas) within the lung. QHC is a measure of HC within the lung. QILD is the sum of QLF, QGGO, and QHC. Quantification of HRCT scans will be performed centrally via a machine learning algorithm. QILD \[%\] is the QILD volume \[mL\] as a percent of the total lung volume. A higher QILD percentage or volume indicates a higher extent of disease.
Absolute change from baseline in quantitative interstitial lung disease (QILD) score [%] on high-resolution computed tomography (HRCT) at Week 26
时间窗: At baseline and at Week 26
QILD will be assessed via quantitative high-resolution computed tomography (qHRCT). QILD are quantitative measures of different radiological patterns associated with lung fibrosis. QLF is a measure of reticulation with architectural distortion. QGGO is a measure of ground glass opacities (i.e. hazy or cloudy areas) within the lung. QHC is a measure of HC within the lung. QILD is the sum of QLF, QGGO, and QHC. Quantification of HRCT scans will be performed centrally via a machine learning algorithm. QILD \[%\] is the QILD volume \[mL\] as a percent of the total lung volume. A higher QILD percentage or volume indicates a higher extent of disease.
次要结局
- Absolute change from baseline in quantitative lung fibrosis (QLF) score [%] on HRCT at Week 26(At baseline and at Week 26)
- Absolute change from baseline in quantitative ground glass opacity (QGGO) score [%] on HRCT at Week 26(At baseline and at Week 26)
- Absolute change from baseline in vascular volume [%] on HRCT at Week 26(At baseline and at Week 26)
- Absolute change from baseline in forced vital capacity (FVC) [mL] at Week 26(At baseline and at Week 26)
- Absolute change from baseline in supplemental oxygen use over the whole trial for oxygen users at baseline(At baseline and at Week 52)
- Time to first supplemental oxygen use during the trial for oxygen non-users at baseline(Up to Week 52)
- Occurrence of infection-related adverse events (AEs) from baseline over the duration of the trial(Up to 1 year)
- Absolute change from baseline in forced vital capacity (FVC) [mL] at Week 26(At baseline and at Week 26)
- Absolute change from baseline in quantitative lung fibrosis (QLF) score [%] on HRCT at Week 26(At baseline and at Week 26)
- Absolute change from baseline in quantitative ground glass opacity (QGGO) score [%] on HRCT at Week 26(At baseline and at Week 26)
- Absolute change from baseline in supplemental oxygen use over the whole trial for oxygen users at baseline(At baseline and at Week 52)
- Time to first supplemental oxygen use during the trial for oxygen non-users at baseline(Up to Week 52)
- Occurrence of infection-related adverse events (AEs) from baseline over the duration of the trial(Up to 1 year)