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A Study of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing Interstitial Lung Disease

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ClinicalTrials.gov Identifier: NCT03099187
Recruitment Status : Active, not recruiting
First Posted : April 4, 2017
Last Update Posted : July 11, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief 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).

Condition or disease Intervention/treatment Phase
Lung Diseases, Interstitial Drug: Pirfenidone Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Multicenter, International, Double-blind, Two-Arm, Randomized, Placebo-controlled Phase II Trial of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing ILD
Actual Study Start Date : May 15, 2017
Estimated Primary Completion Date : February 4, 2020
Estimated Study Completion Date : February 4, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Pirfenidone

Arm Intervention/treatment
Experimental: 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.
Drug: Pirfenidone
Pirfenidone 267 mg capsules three times in a day.

Experimental: 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.
Drug: Placebo
Matching placebo capsules three times in a day.




Primary Outcome Measures :
  1. Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period [ Time Frame: Up to Week 24 ]
    Rate of decline in FVC will be measured in mL by daily handheld spirometer.


Secondary Outcome Measures :
  1. Change in Percent Predicted FVC [ Time Frame: Baseline (Day 1) to Week 24 ]
    FVC will be measured in mL by daily handheld spirometer as well as by spirometry.

  2. Categorical Change in FVC of >5% During Clinic Visits [ Time Frame: Baseline (Day 1) to Week 24 ]
    Categorical change in FVC will be measured both by daily spirometry as well as by spirometry.

  3. Categorical Change in FVC of >10% During Clinic Visits [ Time Frame: Baseline (Day 1) to Week 24 ]
    Categorical change in FVC will be measured both by daily spirometry as well as by spirometry.

  4. Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) [ Time Frame: Baseline (Day 1) to Week 24 ]
    The DLco is a pulmonary function test that measures the capacity for the lung to carry out gas exchange between the inhaled breath and the pulmonary capillary blood vessels and the DLco %-predicted represents the DLco expressed as a percentage of the expected normal valued based on the participant's age, height, gender and ethnicity.

  5. Change in 6-minute Walk Distance (6MWD) [ Time Frame: Baseline (Day 1) to Week 24 ]
    Comparison of 6-minute walk distance before beginning and after completing study therapy.

  6. Change in University of California, San Diego-Shortness of Breath Questionnaire Score [ Time Frame: Baseline (Day 1) to Week 24 ]
    University of California, San Diego Shortness of Breath Questionnaire (SOBQ) consists of 24-item on a scale of 0 to 5 with 0=not at all and 5=maximal or unable to do because of breathlessness. The total scores is calculated by summation of the 24 items scores and transformed into 0-100, with 0= poor quality of life , and 100= excellent quality of life.

  7. Change in Score in Leicester Cough Questionnaire Score [ Time Frame: Baseline (Day 1) to Week 24 ]
    The Leicester Cough Questionnaire is a patient-reported questionnaire evaluating the impact of cough on quality of life. The questionnaire comprises 19 items. Each item assesses symptoms, or the impact of symptoms, over the last 2 weeks on a seven-point Likert scale. Scores in three domains (physical, psychological and social) are calculated as a mean for each domain (range 1 to 7). A total score (range 3 to 21) is also calculated by adding the domain scores together. Higher scores indicate better quality of life.

  8. Change in Cough Visual Analog Scale (VAS) Score [ Time Frame: Baseline (Day 1) to Week 24 ]
    Cough VAS are 100-mm linear scales on which participants indicate the severity of their cough; 0 mm represents no cough and 100 mm the worst cough ever.

  9. Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) [ Time Frame: Baseline (Day 1) to Week 24 ]
    SGRQ is a health related quality of life questionnaire consisting of 40 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status.

  10. Number of Participants with Non-elective Hospitalization, Both Respiratory and all Cause [ Time Frame: Up to Week 91 ]
    Participants with non-elective hospitalization will be reported.

  11. Percentage of Participants with Investigator-reported Acute Exacerbations [ Time Frame: Baseline (Day 1) to Week 24 ]
    Percentage of participants with acute exacerbation will be reported.

  12. Time to First Investigator-reported Acute Exacerbations [ Time Frame: Baseline (Day 1) to Week 24 ]
    Time to first investigator reported acute exacerbations from start of treatment will be reported.

  13. Progression-free Survival (PFS) [ Time Frame: Baseline (Day 1) to Week 24 ]
    PFS is 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.

  14. Progression-free Survival (PFS) [ Time Frame: Baseline (Day 1) to Week 24 ]
    PFS is defined as the time to the first occurrence of a >10% absolute decline in percent predicted FVC, non-elective respiratory hospitalization, or death.

  15. Time to Death From any Cause [ Time Frame: Up to Week 91 ]
    Time to first documented death from start of treatment will be reported.

  16. Time to Death from Respiratory Diseases [ Time Frame: Up to Week 91 ]
    Time to first documented death due to respiratory diseases from start of treatment will be reported.

  17. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline (Day 1) up to Week 80 ]
    An adverse events is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  18. Number of Participants With Dose Reductions and Treatment Interruptions [ Time Frame: From administration of the first dose of study drug to Week 24 ]
    Number of participants with dose reduction and treatment interruptions will be reported.

  19. Number of Participants With Abnormalities in 12-lead Electrocardiogram (ECG) [ Time Frame: Screening to Week 24 ]
    Number of participants with abnormalities in ECG will be reported.

  20. Number of Participants Withdrawn from Trial Treatment or Trial Discontinuations [ Time Frame: Up to Week 91 ]
    Number of participants withdrawn from trial treatment or trial discontinuations will be reported.



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03099187


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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03099187     History of Changes
Other Study ID Numbers: MA39189
2016-002744-17 ( EudraCT Number )
First Posted: April 4, 2017    Key Record Dates
Last Update Posted: July 11, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Interstitial
Respiratory Tract Diseases
Pirfenidone
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents