E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fibrosing interstitial lung disease (ILD) of unknown origin |
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E.1.1.1 | Medical condition in easily understood language |
Interstitial lung disease is a group of lung diseases affecting the interstitium (the tissue and space around the air sacs of the lungs). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022611 |
E.1.2 | Term | Interstitial lung disease |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To evaluate the effect of pirfenidone versus (vs.) placebo on lung function parameters |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of pirfenidone vs. placebo from baseline (Day 1) until Week 24 on other functional parameters, outcomes, and patient-reported outcomes
•To evaluate the safety of pirfenidone vs. placebo
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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 patient 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 within the last 12 months
-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 contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 58 days after the last dose of trial treatment
-For men, agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm
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E.4 | Principal exclusion criteria |
-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 at least 4 weeks prior to the screening period. Patients 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
-Patients previously treated with pirfenidone or nintedanib
-Patients 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 co-existent emphysema (extent greater than extent of fibrosis on high-resolution computed tomography within the last 12 months)
-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 millilitre (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
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of decline in FVC measured in mL by daily handheld spirometer over the 24-week double-blind treatment period |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.Change in percent predicted FVC and in mL measured by spirometry during clinic visits
2.Categorical change in FVC of > 5% , measured both by daily spirometry as well as by spirometry during clinic visits
3.Categorical change in FVC of > 10%, measured both by daily spirometry as well as by spirometry during clinic visits
4.Change in percent predicted DLco
5.Change in 6MWD in meters
6.Change in University of California, San Diego-Shortness of Breath Questionnaire score
7.Change in score in Leicester Cough Questionnaire
8.Change in cough visual analog scale
9.Change in total and sub-scores of the St. George's Respiratory Questionnaire
10.Number of participants with non-elective hospitalization, both respiratory and all cause
11.Incidence of, and time to first, investigator-reported acute exacerbations
12.Progression-free survival (PFS), defined as the time to the first occurrence of a >10% absolute decline in percent predicted FVC, a >50 m decline of 6MWD, or death
13.PFS, alternatively defined as the time to the first occurrence of a >10% absolute decline in percent predicted FVC, non-elective respiratory hospitalization, or death
14.Time to death from any cause
15.Time to death from respiratory diseases
16.Nature, frequency, severity, and timing of treatment-emergent adverse events
17.Dose reductions and treatment interruptions
18.Abnormalities in clinical laboratory test results
19.Abnormalities in 12-lead ECG
20.Number of participants withdrawn from trial treatment or trial discontinuations
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5. Screening (Days -21 to -1) to Week 24
6-9. Week 1 (Day 1) to Week 24
10. Up to Week 91
11-13. Week 1 (Day 1) to Week 24
14-16. Up to Week 91
17. Week 1 to Week 24
18. Screening to Week 24
19. Screening to Week 28
20. Up to Week 91
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Assessments of the exploratory biomarkers and their relationship with drug responses |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Canada |
Czech Republic |
Denmark |
Germany |
Ireland |
Israel |
Italy |
Poland |
Portugal |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the clinical trial is defined as the date when the last patient, last visit (LPLV) occurs or the date at which the last data point which is required for the statistical analysis is received, whichever is the later date. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |