A Study of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing Interstitial Lung Disease
Condition: Lung Diseases, Interstitial
MeSH terms: Lung Diseases; Lung Diseases, Interstitial
Intervention: Pirfenidone; Placebo
Intervention description: Pirfenidone 267 mg capsules three times in a day.; Matching placebo capsules three times in a day.
Intervention MeSH terms: Pirfenidone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 253.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      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).
    

Eligibility criteria:

        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 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

        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 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