Multicenter, International, Double-blind, Two-Arm, Randomized, Placebo-controlled Phase II Trial of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing ILD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 253
- 试验地点
- 66
- 主要终点
- Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of pirfenidone in participants with fibrosing interstitial lung disease (ILD) who cannot be classified with moderate or high confidence into any other category of fibrosing ILD by multidisciplinary team (MDT) review ("unclassifiable" ILD).
详细描述
Study participants will be randomised to receive 801 mg pirfenidone or placebo three times daily for 24 weeks. The efficacy of pirfenidone versus placebo will be assessed by daily measurement of forced vital capacity using a handheld spirometer over the treatment period. Additionally, the study will assess the efficacy and safety of pirfenidone with and without concomitant mycophenolate mofetil treatment and in study participants with or without interstitial pneumonia with autoimmune features (IPAF). All study participants who attend the follow-up visit at Week 28 will be offered the opportunity to receive open-label pirfenidone within the trial protocol. In order to maintain blinding of the controlled period of the study, all study participants will discontinue treatment by Week 24 and return for a follow-up visit 4 weeks later. Study participants eligible to participate in the single-arm 12-month extension will be initiated on open-label pirfenidone during this visit (re-starting the dose titration from one capsule three times daily [TID]). During the long-term extension period, study participants will be monitored for safety, initially at monthly visits during the first 6 months and thereafter approximately every 3 months. A final follow-up visit will take place 4 weeks after the last dose of pirfenidone is taken.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18-85 years
- •Confirmed fibrosing ILD which, following multidisciplinary team review, cannot be classified with either high or moderate confidence as a specific idiopathic interstitial pneumonia or other defined ILD
- •Progressive disease as considered by the investigator as participants deterioration within the last 6 months, which is defined as a rate of decline in forced vital capacity (FVC) >5% or a significant symptomatic worsening not due to cardiac, pulmonary vascular or other causes
- •Extent of fibrosis >10% on high-resolution computed tomography
- •Forced vital capacity >= 45% of predicted value
- •Diffusing capacity of the lung for carbon monoxide (DLco) >= 30% of predicted value
- •Forced expiratory volume in 1 second/FVC ratio >= 0.7
- •Able to do 6-minute walk distance (6MWD) >= 150 meters
- •For women of childbearing potential: agreement to remain abstinent or use a non-hormonal or hormonal contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of pirfenidone
- •For men, agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm
排除标准
- •Diagnosis with moderate or high confidence of nonspecific interstitial pneumonia and any ILD with an identifiable cause such as connective tissue disease-ILD, chronic hypersensitivity pneumonitis, or others
- •Diagnosis of idiopathic pulmonary fibrosis independent of the confidence level
- •History of unstable angina or myocardial infarction during the previous 6 months
- •Treatment with high dose systemic corticosteroids, or any immunosuppressant other than mycophenolate mofetil/acid (MMF), at any time within the 4 weeks of the screening period. Participants being treated with MMF should be on a stable dose that is expected to remain stable throughout the trial and was started at least 3 months prior to screening
- •Participants previously treated with pirfenidone or nintedanib
- •Participants treated with N-acetyl-cysteine for fibrotic lung disease, at any time within the 4 weeks of the screening period
- •Drug treatment for any type of pulmonary hypertension
- •Participation in a trial of an investigational medicinal product within the last 4 weeks
- •Significant other organ co-morbidity including hepatic or renal impairment
- •Predicted life expectancy < 12 months or on an active transplant waiting list
- •Use of any tobacco product in the 12 weeks prior to the start of screening, or any unwillingness to abstain from their use through to the Follow-up Visit
- •Illicit drug or alcohol abuse within 12 months prior to screening
- •Planned major surgery during the trial
- •Hypersensitivity to the active substance or to any of the excipients of pirfenidone
- •History of angioedema
- •Concomitant use of fluvoxamine
- •Clinical evidence of any active infection
- •Any history of hepatic impairment, elevation of transaminase enzymes, or liver function test results as: Total bilirubin above the upper limit of normal (ULN), Aspartate aminotransferase or alanine aminotransferase >1.5 × ULN, and Alkaline phosphatase >2.0 × ULN
- •Creatinine clearance < 30 milliliter (mL) per minute, calculated using the Cockcroft-Gault formula
- •Any serious medical condition, clinically significant abnormality on an Electrocardiogram (ECG) at screening, or laboratory test results
- •An ECG with a heart rate corrected QT interval using Fridericia's formula as >= 500 milliseconds at screening, or a family or personal history of long QT syndrome
研究组 & 干预措施
Pirfenidone
Participants will receive pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
干预措施: Pirfenidone (Drug)
Placebo
Participants will receive matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.
干预措施: Placebo (Drug)
结局指标
主要结局
Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period
时间窗: Up to Week 24
Rate of decline in FVC was measured in mL by daily handheld spirometer. The analyses were repeated due to an additional independent review of the home spirometry data.
次要结局
- Change in Cough Visual Analog Scale (VAS) Score(Baseline (Day 1) to Week 24)
- Categorical Change in FVC of >5%(Baseline (Day 1) to Week 24)
- Change in University of California, San Diego-Shortness of Breath Questionnaire Score(Baseline (Day 1) to Week 24)
- Change in Score in Leicester Cough Questionnaire Score(Baseline (Day 1) to Week 24)
- Change in 6-minute Walk Distance (6MWD)(Baseline (Day 1) to Week 24)
- Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause(Baseline (Day 1) to Week 24)
- Change in Percent Predicted FVC(Baseline (Day 1) to Week 24)
- Change in FVC(Baseline (Day 1) to Week 24)
- Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco)(Baseline (Day 1) to Week 24)
- Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ)(Baseline (Day 1) to Week 24)
- Percentage of Participants With Investigator-reported Acute Exacerbations(Baseline (Day 1) to Week 24)
- Time to First Investigator-reported Acute Exacerbations(Baseline (Day 1) to Week 24)
- Time to Death From Respiratory Diseases(Baseline (Day 1) to Week 24)
- Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period(From administration of the first dose of study drug to Week 24)
- Categorical Change in FVC of >10%(Baseline (Day 1) to Week 24)
- Progression-free Survival (PFS)(Baseline (Day 1) to Week 24)
- Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up(From the Follow-up Visit at Week 28 through the follow-up period of 12 Months)
- Time to Death From Any Cause(Baseline (Day 1) to Week 24)
- Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the Double-Blind Period(Baseline (Day 1) to Week 24)
- Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the 12-month Safety Follow-up(From the Follow-up Visit at Week 28 through the follow-up period of 12 Months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Baseline (Day 1) to Week 28)