Lung Diseases, Interstitial
Conditions
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).
Detailed description
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.
Interventions
DRUGPirfenidone
Pirfenidone 267 mg capsules three times in a day.
DRUGPlacebo
Matching placebo capsules three times in a day.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in FVC | Baseline (Day 1) to Week 24 | FVC was measured in liter (L) by spirometry. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis. |
| Categorical Change in FVC of >5% | Baseline (Day 1) to Week 24 | Categorical change in FVC was measured both by daily spirometry as well as by spirometry during clinical visits. Only the site spirometry data were used as the daily spirometry data were not normally distributed. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis. |
| Categorical Change in FVC of >10% | Baseline (Day 1) to Week 24 | Categorical change in FVC was measured both by daily spirometry as well as by spirometry during clinical visits. Only the site spirometry data were used as the daily spirometry data were not normally distributed. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis. |
| Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) | 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. |
| Change in 6-minute Walk Distance (6MWD) | Baseline (Day 1) to Week 24 | Comparison of 6-minute walk distance before beginning and after completing study therapy. |
| Change in University of California, San Diego-Shortness of Breath Questionnaire Score | 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 were 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. |
| Change in Score in Leicester Cough Questionnaire Score | 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) were calculated as a mean for each domain (range 1 to 7). A total score (range 3 to 21) was also calculated by adding the domain scores together. Higher scores indicate better quality of life. |
| Change in Cough Visual Analog Scale (VAS) Score | 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. |
| Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Baseline (Day 1) to Week 24 | The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in participants with diseases of airways obstruction. Three component scores are: Symptoms (respiratory symptoms and severity); Activity (activities that cause or are limited by breathlessness); Impacts (social functioning and psychological disturbances due to airway disease). Each component sub-scores are calculated from the summed weights for the positive responses to questions. Total score summaries the impact of disease on overall health status. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. It is calculated by summing all positive responses in the questionnaire and expressing the result as a percentage of the total weight for the questionnaire. |
| Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause | Baseline (Day 1) to Week 24 | Participants with non-elective hospitalization are reported. |
| Change in Percent Predicted FVC | Baseline (Day 1) to Week 24 | FVC was measured in liter (L) by spirometry. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis. |
| Time to First Investigator-reported Acute Exacerbations | Baseline (Day 1) to Week 24 | Time to first investigator reported acute exacerbations from start of treatment are reported. |
| Progression-free Survival (PFS) | 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. |
| Time to Death From Any Cause | Baseline (Day 1) to Week 24 | Time to first documented death from start of treatment is reported. |
| Time to Death From Respiratory Diseases | Baseline (Day 1) to Week 24 | Time to first documented death due to respiratory diseases from start of treatment will be reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Baseline (Day 1) to Week 28 | An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
| 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 | Number of participants with dose reduction and treatment interruptions are reported. |
| 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 | Number of participants with dose reduction and treatment interruptions are reported. |
| 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 are reported. |
| 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 withdrawn from trial treatment or trial discontinuations are reported. |
| Percentage of Participants With Investigator-reported Acute Exacerbations | Baseline (Day 1) to Week 24 | Percentage of participants with acute exacerbation arereported. |
Countries
Australia, Belgium, Canada, Czechia, Denmark, Germany, Greece, Ireland, Israel, Italy, Poland, Portugal, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pirfenidone Participants received 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. After participants completed the double-blind treatment period and the follow-up visit at Week 28, they were offered the option to receive open-label pirfenidone within the trial protocol in a safety follow-up period of up to 12 months. A final follow-up visit was performed at the end of the safety period, 28 days after the last open-label dose. | 127 |
| Placebo Participants received 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. After participants completed the double-blind treatment period and the follow-up visit at Week 28, they were offered the option to receive open-label pirfenidone within the trial protocol in a safety follow-up period of up to 12 months. A final follow-up visit was performed at the end of the safety period, 28 days after the last open-label dose. | 126 |
| Total | 253 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 12-month Safety Follow-up | Adverse Event | 0 | 0 | 5 | 12 |
| 12-month Safety Follow-up | Death | 0 | 0 | 7 | 9 |
| 12-month Safety Follow-up | Due to hospitalization | 0 | 0 | 0 | 1 |
| 12-month Safety Follow-up | Lost to Follow-up | 0 | 0 | 1 | 0 |
| 12-month Safety Follow-up | Lung transplantation | 0 | 0 | 2 | 1 |
| 12-month Safety Follow-up | Symptomatic deterioration | 0 | 0 | 1 | 1 |
| 12-month Safety Follow-up | Withdrawal by Subject | 0 | 0 | 3 | 2 |
| Double-blind Treatment | Adverse Event | 19 | 1 | 0 | 0 |
| Double-blind Treatment | Death | 1 | 3 | 0 | 0 |
| Double-blind Treatment | Disease progression | 0 | 1 | 0 | 0 |
| Double-blind Treatment | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Double-blind Treatment | Lung transplantation | 0 | 1 | 0 | 0 |
| Double-blind Treatment | Non-compliance with Protocol procedure | 1 | 1 | 0 | 0 |
| Double-blind Treatment | Non-compliance with study drug | 0 | 2 | 0 | 0 |
| Double-blind Treatment | Physician Decision | 2 | 1 | 0 | 0 |
| Double-blind Treatment | Randomization error | 0 | 2 | 0 | 0 |
| Double-blind Treatment | Withdrawal by Subject | 9 | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Pirfenidone | Placebo |
|---|---|---|---|
| Age, Continuous | 67.8 Years STANDARD_DEVIATION 9.6 | 68.0 Years STANDARD_DEVIATION 10.1 | 67.7 Years STANDARD_DEVIATION 9.2 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 16 Participants | 7 Participants | 9 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 227 Participants | 115 Participants | 112 Participants |
| Race/Ethnicity, Customized Not reported | 10 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 243 Participants | 120 Participants | 123 Participants |
| Sex: Female, Male Female | 114 Participants | 57 Participants | 57 Participants |
| Sex: Female, Male Male | 139 Participants | 70 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 127 | 7 / 124 | 7 / 94 | 9 / 110 |
| other Total, other adverse events | 107 / 127 | 81 / 124 | 64 / 94 | 86 / 110 |
| serious Total, serious adverse events | 18 / 127 | 20 / 124 | 26 / 94 | 27 / 110 |
Outcome results
Primary
Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period
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.
Time frame: Up to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pirfenidone | Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period | Primary Analysis in 2019 | -17.9 milliliter (mL) |
| Pirfenidone | Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period | Final Analysis in 2020 | -90.3 milliliter (mL) |
| Placebo | Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period | Primary Analysis in 2019 | 116.6 milliliter (mL) |
| Placebo | Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period | Final Analysis in 2020 | 125.6 milliliter (mL) |
Comparison: Primary Analysis in 2019. Mean FVC decline comparison between treatment groups using a Student's t-test with a two-sided significance level of 0.05p-value: 0.677795% CI: [-772.4, 503.3]t-test, 2 sided
Comparison: Final Analysis in 2020. Mean FVC decline comparison between treatment groups using a Student's t-test with a two-sided significance level of 0.05p-value: 0.468295% CI: [-803.6, 371.7]Student's t-test
Secondary
Categorical Change in FVC of >10%
Categorical change in FVC was measured both by daily spirometry as well as by spirometry during clinical visits. Only the site spirometry data were used as the daily spirometry data were not normally distributed. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pirfenidone | Categorical Change in FVC of >10% | Primary Analysis in 2019 | 18 Number of Participants |
| Pirfenidone | Categorical Change in FVC of >10% | Final Analysis in 2020 | 18 Number of Participants |
| Placebo | Categorical Change in FVC of >10% | Primary Analysis in 2019 | 34 Number of Participants |
| Placebo | Categorical Change in FVC of >10% | Final Analysis in 2020 | 33 Number of Participants |
Comparison: Primary Analysis in 2019p-value: 0.011495% CI: [0.23, 0.84]Cochran-Mantel-Haenszel
Comparison: Final Analysis in 2020p-value: 0.016895% CI: [0.24, 0.88]Cochran-Mantel-Haenszel
Secondary
Categorical Change in FVC of >5%
Categorical change in FVC was measured both by daily spirometry as well as by spirometry during clinical visits. Only the site spirometry data were used as the daily spirometry data were not normally distributed. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pirfenidone | Categorical Change in FVC of >5% | Primary Analysis in 2019 | 47 Number of Participants |
| Pirfenidone | Categorical Change in FVC of >5% | Final Analysis in 2020 | 47 Number of Participants |
| Placebo | Categorical Change in FVC of >5% | Primary Analysis in 2019 | 74 Number of Participants |
| Placebo | Categorical Change in FVC of >5% | Final Analysis in 2020 | 73 Number of Participants |
Comparison: Primary Analysis in 2019p-value: 0.000695% CI: [0.25, 0.69]Cochran-Mantel-Haenszel
Comparison: Final Analysis in 2020p-value: 0.000995% CI: [0.26, 0.71]Cochran-Mantel-Haenszel
Secondary
Change in 6-minute Walk Distance (6MWD)
Comparison of 6-minute walk distance before beginning and after completing study therapy.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pirfenidone | Change in 6-minute Walk Distance (6MWD) | Change from Baseline at Week 12 | -14.8 meter (m) | Standard Deviation 66.23 |
| Pirfenidone | Change in 6-minute Walk Distance (6MWD) | Change from Baseline at Week 24 | -2.0 meter (m) | Standard Deviation 68.11 |
| Pirfenidone | Change in 6-minute Walk Distance (6MWD) | Baseline | 391.6 meter (m) | Standard Deviation 114.93 |
| Placebo | Change in 6-minute Walk Distance (6MWD) | Change from Baseline at Week 12 | -7.7 meter (m) | Standard Deviation 57.6 |
| Placebo | Change in 6-minute Walk Distance (6MWD) | Baseline | 394.0 meter (m) | Standard Deviation 108.09 |
| Placebo | Change in 6-minute Walk Distance (6MWD) | Change from Baseline at Week 24 | -26.7 meter (m) | Standard Deviation 79.32 |
Comparison: Primary Analysis in 2019p-value: 0.0395rank ANCOVA
Comparison: Final Analysis in 2020p-value: 0.0299rank ANCOVA
Secondary
Change in Cough Visual Analog Scale (VAS) Score
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.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pirfenidone | Change in Cough Visual Analog Scale (VAS) Score | Baseline | 35.60 millimeter (mm) | Standard Deviation 27.497 |
| Pirfenidone | Change in Cough Visual Analog Scale (VAS) Score | Change from Baseline at Week 12 | -4.33 millimeter (mm) | Standard Deviation 20.017 |
| Pirfenidone | Change in Cough Visual Analog Scale (VAS) Score | Change from Baseline at Week 24 | -2.52 millimeter (mm) | Standard Deviation 26.72 |
| Placebo | Change in Cough Visual Analog Scale (VAS) Score | Baseline | 37.18 millimeter (mm) | Standard Deviation 26.27 |
| Placebo | Change in Cough Visual Analog Scale (VAS) Score | Change from Baseline at Week 12 | 3.32 millimeter (mm) | Standard Deviation 26.429 |
| Placebo | Change in Cough Visual Analog Scale (VAS) Score | Change from Baseline at Week 24 | 0.78 millimeter (mm) | Standard Deviation 30.121 |
Comparison: Primary Analysis in 2019p-value: 0.299595% CI: [-10, 4]rank ANCOVA
Comparison: Final Analysis in 2020p-value: 0.337295% CI: [-10, 4]rank ANCOVA
Secondary
Change in FVC
FVC was measured in liter (L) by spirometry. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pirfenidone | Change in FVC | Baseline | 2.36 Liter (L) | Standard Deviation 0.793 |
| Pirfenidone | Change in FVC | Week 16 | 2.41 Liter (L) | Standard Deviation 0.86 |
| Pirfenidone | Change in FVC | Week 4 | 2.37 Liter (L) | Standard Deviation 0.818 |
| Pirfenidone | Change in FVC | Week 20 | 2.40 Liter (L) | Standard Deviation 0.866 |
| Pirfenidone | Change in FVC | Week 12 | 2.37 Liter (L) | Standard Deviation 0.82 |
| Pirfenidone | Change in FVC | Week 24 | 2.37 Liter (L) | Standard Deviation 0.863 |
| Pirfenidone | Change in FVC | Week 8 | 2.37 Liter (L) | Standard Deviation 0.822 |
| Placebo | Change in FVC | Week 24 | 2.34 Liter (L) | Standard Deviation 0.773 |
| Placebo | Change in FVC | Baseline | 2.38 Liter (L) | Standard Deviation 0.747 |
| Placebo | Change in FVC | Week 4 | 2.37 Liter (L) | Standard Deviation 0.786 |
| Placebo | Change in FVC | Week 8 | 2.36 Liter (L) | Standard Deviation 0.816 |
| Placebo | Change in FVC | Week 12 | 2.35 Liter (L) | Standard Deviation 0.773 |
| Placebo | Change in FVC | Week 16 | 2.31 Liter (L) | Standard Deviation 0.782 |
| Placebo | Change in FVC | Week 20 | 2.30 Liter (L) | Standard Deviation 0.796 |
Comparison: Primary Analysis in 2019p-value: 0.001895% CI: [35.9, 154.6]Student's t-test
Comparison: Final Analysis in 2020p-value: 0.009695% CI: [20.7, 147.8]Student's t-test
Secondary
Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco)
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.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pirfenidone | Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) | Change from Baseline at Week 12 (Primary Analysis in 2019) | -0.52 % predicted | Standard Deviation 6.193 |
| Pirfenidone | Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) | Change from Baseline at Week 12 (Final Analysis in 2020) | -0.52 % predicted | Standard Deviation 6.193 |
| Pirfenidone | Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) | Change from Baseline at Week 24 (Primary Analysis in 2019) | -0.65 % predicted | Standard Deviation 7.113 |
| Pirfenidone | Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) | Change from Baseline at Week 24 (Final Analysis in 2020) | -0.65 % predicted | Standard Deviation 7.113 |
| Pirfenidone | Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) | Baseline (Day 1) | 46.19 % predicted | Standard Deviation 12.403 |
| Placebo | Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) | Change from Baseline at Week 24 (Final Analysis in 2020) | -2.48 % predicted | Standard Deviation 8.893 |
| Placebo | Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) | Baseline (Day 1) | 49.57 % predicted | Standard Deviation 13.931 |
| Placebo | Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) | Change from Baseline at Week 12 (Primary Analysis in 2019) | -0.56 % predicted | Standard Deviation 8.807 |
| Placebo | Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) | Change from Baseline at Week 24 (Primary Analysis in 2019) | -2.47 % predicted | Standard Deviation 8.833 |
| Placebo | Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) | Change from Baseline at Week 12 (Final Analysis in 2020) | -0.89 % predicted | Standard Deviation 9.407 |
Comparison: Primary Analysis in 2019p-value: 0.0874rank ANCOVA
Comparison: Final Analysis in 2020p-value: 0.1191rank ANCOVA
Secondary
Change in Percent Predicted FVC
FVC was measured in liter (L) by spirometry. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pirfenidone | Change in Percent Predicted FVC | Week 4 | 74.04 Percent predicted (%) | Standard Deviation 19.009 |
| Pirfenidone | Change in Percent Predicted FVC | Week 16 | 74.56 Percent predicted (%) | Standard Deviation 20.299 |
| Pirfenidone | Change in Percent Predicted FVC | Baseline (Day 1) | 73.95 Percent predicted (%) | Standard Deviation 18.815 |
| Pirfenidone | Change in Percent Predicted FVC | Week 20 | 73.94 Percent predicted (%) | Standard Deviation 21 |
| Pirfenidone | Change in Percent Predicted FVC | Week 8 | 73.98 Percent predicted (%) | Standard Deviation 19.324 |
| Pirfenidone | Change in Percent Predicted FVC | Week 24 | 72.95 Percent predicted (%) | Standard Deviation 20.819 |
| Pirfenidone | Change in Percent Predicted FVC | Week 12 | 73.96 Percent predicted (%) | Standard Deviation 19.493 |
| Placebo | Change in Percent Predicted FVC | Week 24 | 73.55 Percent predicted (%) | Standard Deviation 22.383 |
| Placebo | Change in Percent Predicted FVC | Baseline (Day 1) | 73.95 Percent predicted (%) | Standard Deviation 19.974 |
| Placebo | Change in Percent Predicted FVC | Week 4 | 74.55 Percent predicted (%) | Standard Deviation 21.223 |
| Placebo | Change in Percent Predicted FVC | Week 12 | 73.91 Percent predicted (%) | Standard Deviation 20.856 |
| Placebo | Change in Percent Predicted FVC | Week 16 | 72.65 Percent predicted (%) | Standard Deviation 22.479 |
| Placebo | Change in Percent Predicted FVC | Week 20 | 71.99 Percent predicted (%) | Standard Deviation 21.673 |
| Placebo | Change in Percent Predicted FVC | Week 8 | 73.50 Percent predicted (%) | Standard Deviation 20.168 |
Comparison: Primary Analysis in 2019p-value: 0.0383rank ANCOVA
Comparison: Final Analysis in 2020p-value: 0.0239rank ANCOVA
Secondary
Change in Score in Leicester Cough Questionnaire Score
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) were calculated as a mean for each domain (range 1 to 7). A total score (range 3 to 21) was also calculated by adding the domain scores together. Higher scores indicate better quality of life.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pirfenidone | Change in Score in Leicester Cough Questionnaire Score | Change from Baseline at Week 12 (Primary Analysis in 2019) | 0.35 Scores on a Scale | Standard Deviation 2.903 |
| Pirfenidone | Change in Score in Leicester Cough Questionnaire Score | Change from Baseline at Week 12 (Final Analysis in 2020) | 0.35 Scores on a Scale | Standard Deviation 2.903 |
| Pirfenidone | Change in Score in Leicester Cough Questionnaire Score | Baseline | 16.13 Scores on a Scale | Standard Deviation 3.711 |
| Pirfenidone | Change in Score in Leicester Cough Questionnaire Score | Change from Baseline at Week 24 (Final Analysis in 2020) | 0.35 Scores on a Scale | Standard Deviation 2.884 |
| Pirfenidone | Change in Score in Leicester Cough Questionnaire Score | Change from Baseline at Week 24 (Primary Analysis in 2019) | 0.36 Scores on a Scale | Standard Deviation 2.889 |
| Placebo | Change in Score in Leicester Cough Questionnaire Score | Change from Baseline at Week 24 (Final Analysis in 2020) | 0.04 Scores on a Scale | Standard Deviation 3.702 |
| Placebo | Change in Score in Leicester Cough Questionnaire Score | Baseline | 15.15 Scores on a Scale | Standard Deviation 3.928 |
| Placebo | Change in Score in Leicester Cough Questionnaire Score | Change from Baseline at Week 12 (Primary Analysis in 2019) | -0.23 Scores on a Scale | Standard Deviation 3.654 |
| Placebo | Change in Score in Leicester Cough Questionnaire Score | Change from Baseline at Week 24 (Primary Analysis in 2019) | 0.04 Scores on a Scale | Standard Deviation 3.702 |
| Placebo | Change in Score in Leicester Cough Questionnaire Score | Change from Baseline at Week 12 (Final Analysis in 2020) | -0.23 Scores on a Scale | Standard Deviation 3.654 |
Comparison: Primary Analysis in 2019p-value: 0.187295% CI: [-0.45, 1.04]rank ANCOVA
Comparison: Final Analysis in 2020p-value: 0.201995% CI: [-0.48, 1.02]rank ANCOVA
Secondary
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ)
The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in participants with diseases of airways obstruction. Three component scores are: Symptoms (respiratory symptoms and severity); Activity (activities that cause or are limited by breathlessness); Impacts (social functioning and psychological disturbances due to airway disease). Each component sub-scores are calculated from the summed weights for the positive responses to questions. Total score summaries the impact of disease on overall health status. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. It is calculated by summing all positive responses in the questionnaire and expressing the result as a percentage of the total weight for the questionnaire.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Symptoms sub-score at Week 24 | -1.69 Scores of a Scale | Standard Deviation 19.186 |
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Impacts sub-score - Baseline | 37.12 Scores of a Scale | Standard Deviation 20.484 |
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Impacts sub-score at Week 24 | -0.18 Scores of a Scale | Standard Deviation 13.884 |
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Impacts sub-score at Week 12 | 0.29 Scores of a Scale | Standard Deviation 16.826 |
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Activities sub-score - Baseline | 63.93 Scores of a Scale | Standard Deviation 20.388 |
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Symptoms sub-score at Week 12 | -2.60 Scores of a Scale | Standard Deviation 19.173 |
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Total score - Baseline | 47.37 Scores of a Scale | Standard Deviation 18.465 |
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Activities sub-score at Week 12 | 1.17 Scores of a Scale | Standard Deviation 13.376 |
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Total score at Week 12 | -0.17 Scores of a Scale | Standard Deviation 13.633 |
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Symptoms sub-score - Baseline | 49.28 Scores of a Scale | Standard Deviation 21.687 |
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Total score at Week 24 | 0.05 Scores of a Scale | Standard Deviation 12.549 |
| Pirfenidone | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Activities sub-score at Week 24 | 1.25 Scores of a Scale | Standard Deviation 14.629 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Total score at Week 24 | 0.85 Scores of a Scale | Standard Deviation 13.383 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Symptoms sub-score - Baseline | 53.10 Scores of a Scale | Standard Deviation 21.45 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Symptoms sub-score at Week 12 | 0.86 Scores of a Scale | Standard Deviation 16.212 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Symptoms sub-score at Week 24 | -0.66 Scores of a Scale | Standard Deviation 15.407 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Activities sub-score - Baseline | 66.96 Scores of a Scale | Standard Deviation 18.615 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Activities sub-score at Week 12 | 1.13 Scores of a Scale | Standard Deviation 13.704 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Activities sub-score at Week 24 | 2.22 Scores of a Scale | Standard Deviation 13.11 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Impacts sub-score - Baseline | 41.47 Scores of a Scale | Standard Deviation 20.52 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Impacts sub-score at Week 12 | 0.33 Scores of a Scale | Standard Deviation 13.888 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Impacts sub-score at Week 24 | 1.07 Scores of a Scale | Standard Deviation 17.539 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Total score - Baseline | 51.46 Scores of a Scale | Standard Deviation 17.699 |
| Placebo | Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ) | Change from Baseline in Total score at Week 12 | 0.53 Scores of a Scale | Standard Deviation 11.724 |
Comparison: Primary Analysis in 2019p-value: 0.16395% CI: [-5.06, 1.38]rank ANCOVA
Comparison: Final Analysis in 2020p-value: 0.185195% CI: [-5, 1.55]rank ANCOVA
Secondary
Change in University of California, San Diego-Shortness of Breath Questionnaire Score
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 were 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.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pirfenidone | Change in University of California, San Diego-Shortness of Breath Questionnaire Score | Baseline | 44.17 Scores on a Scale | Standard Deviation 25.204 |
| Pirfenidone | Change in University of California, San Diego-Shortness of Breath Questionnaire Score | Change from Baseline at Week 12 | 1.47 Scores on a Scale | Standard Deviation 19.707 |
| Pirfenidone | Change in University of California, San Diego-Shortness of Breath Questionnaire Score | Change from Baseline at Week 24 | 5.21 Scores on a Scale | Standard Deviation 18.701 |
| Placebo | Change in University of California, San Diego-Shortness of Breath Questionnaire Score | Baseline | 48.89 Scores on a Scale | Standard Deviation 23.441 |
| Placebo | Change in University of California, San Diego-Shortness of Breath Questionnaire Score | Change from Baseline at Week 12 | 2.24 Scores on a Scale | Standard Deviation 18.617 |
| Placebo | Change in University of California, San Diego-Shortness of Breath Questionnaire Score | Change from Baseline at Week 24 | 5.30 Scores on a Scale | Standard Deviation 22.078 |
Comparison: Primary Analysis in 2019p-value: 0.778895% CI: [-5, 5]rank ANCOVA
Comparison: Final Analysis in 2020p-value: 0.828995% CI: [-5, 5]rank ANCOVA
Secondary
Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up
Number of participants with dose reduction and treatment interruptions are reported.
Time frame: From the Follow-up Visit at Week 28 through the follow-up period of 12 Months
Population: The safety population was defined as all participants with at least one intake of pirfenidone or placebo, i.e., at least one record in the drug-log of the double-blind period with a non-zero dose. Participants in the safety population were assigned to a treatment arm according to the actual treatment they received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pirfenidone | Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up | Participants with at least one dose modification | 41 Number of Participants |
| Pirfenidone | Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up | Participants with at least one dose interruption | 24 Number of Participants |
| Placebo | Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up | Participants with at least one dose modification | 60 Number of Participants |
| Placebo | Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up | Participants with at least one dose interruption | 34 Number of Participants |
Secondary
Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period
Number of participants with dose reduction and treatment interruptions are reported.
Time frame: From administration of the first dose of study drug to Week 24
Population: The safety population was defined as all participants with at least one intake of pirfenidone or placebo, i.e., at least one record in the drug-log of the double-blind period with a non-zero dose. Participants in the safety population were assigned to a treatment arm according to the actual treatment they received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pirfenidone | Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period | Participants with at least one dose modification | 51 Number of Participants |
| Pirfenidone | Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period | Participants with at least one dose interruption | 40 Number of Participants |
| Placebo | Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period | Participants with at least one dose modification | 34 Number of Participants |
| Placebo | Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period | Participants with at least one dose interruption | 12 Number of Participants |
Secondary
Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the 12-month Safety Follow-up
Number of participants withdrawn from trial treatment or trial discontinuations are reported.
Time frame: From the Follow-up Visit at Week 28 through the follow-up period of 12 Months
Population: The safety population was defined as all participants with at least one intake of pirfenidone or placebo, i.e., at least one record in the drug-log of the double-blind period with a non-zero dose. Participants in the safety population were assigned to a treatment arm according to the actual treatment they received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pirfenidone | Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the 12-month Safety Follow-up | 19 Number of Participants |
| Placebo | Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the 12-month Safety Follow-up | 26 Number of Participants |
Secondary
Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the Double-Blind Period
Number of participants withdrawn from trial treatment or trial discontinuations are reported.
Time frame: Baseline (Day 1) to Week 24
Population: The safety population was defined as all participants with at least one intake of pirfenidone or placebo, i.e., at least one record in the drug-log of the double-blind period with a non-zero dose. Participants in the safety population were assigned to a treatment arm according to the actual treatment they received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pirfenidone | Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the Double-Blind Period | 25 Number of Participants |
| Placebo | Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the Double-Blind Period | 12 Number of Participants |
Secondary
Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause
Participants with non-elective hospitalization are reported.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pirfenidone | Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause | All-cause hospitalization | 16 Number of Participants |
| Pirfenidone | Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause | Respiratory-related hospitalization | 5 Number of Participants |
| Placebo | Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause | All-cause hospitalization | 13 Number of Participants |
| Placebo | Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause | Respiratory-related hospitalization | 5 Number of Participants |
Comparison: Primary Analysis in 2019. All-cause non-elective hospitalization.p-value: 0.592295% CI: [0.59, 2.49]Log Rank
Comparison: Primary Analysis in 2019. Respiratory non-elective hospitalization.p-value: 0.805795% CI: [0.26, 2.83]Log Rank
Comparison: Final Analysis in 2020. All-cause non-elective hospitalization.p-value: 0.461395% CI: [0.63, 2.73]Log Rank
Comparison: Final Analysis in 2020. Respiratory non-elective hospitalization.p-value: 0.952395% CI: [0.3, 3.59]Log Rank
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Baseline (Day 1) to Week 28
Population: The safety population was defined as all participants with at least one intake of pirfenidone or placebo, i.e., at least one record in the drug-log of the double-blind period with a non-zero dose. Participants in the safety population were assigned to a treatment arm according to the actual treatment they received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pirfenidone | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 120 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 101 Participants |
Secondary
Percentage of Participants With Investigator-reported Acute Exacerbations
Percentage of participants with acute exacerbation arereported.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pirfenidone | Percentage of Participants With Investigator-reported Acute Exacerbations | 3.9 Percentage of Participants |
| Placebo | Percentage of Participants With Investigator-reported Acute Exacerbations | 5.6 Percentage of Participants |
Secondary
Progression-free Survival (PFS)
PFS is defined as the time to the first occurrence of a \>10% relative decline in percent predicted FVC, non-elective respiratory hospitalization, or death.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pirfenidone | Progression-free Survival (PFS) | NA Week |
| Placebo | Progression-free Survival (PFS) | NA Week |
Comparison: Primary Analysis in 2019p-value: 0.272695% CI: [0.52, 1.2]Log Rank
Comparison: Final Analysis in 2020p-value: 0.338695% CI: [0.54, 1.24]Log Rank
Secondary
Progression-free Survival (PFS)
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.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pirfenidone | Progression-free Survival (PFS) | 25.14 Week |
| Placebo | Progression-free Survival (PFS) | 24.71 Week |
Comparison: Primary Analysis in 2019p-value: 0.36695% CI: [0.56, 1.24]Log Rank
Comparison: Final Analysis in 2020p-value: 0.417395% CI: [0.57, 1.26]Log Rank
Secondary
Time to Death From Any Cause
Time to first documented death from start of treatment is reported.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pirfenidone | Time to Death From Any Cause | NA Week |
| Placebo | Time to Death From Any Cause | NA Week |
p-value: 0.996995% CI: [0.06, 16.08]Log Rank
Secondary
Time to Death From Respiratory Diseases
Time to first documented death due to respiratory diseases from start of treatment will be reported.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pirfenidone | Time to Death From Respiratory Diseases | NA Week |
| Placebo | Time to Death From Respiratory Diseases | NA Week |
p-value: 0.3231Log Rank
Secondary
Time to First Investigator-reported Acute Exacerbations
Time to first investigator reported acute exacerbations from start of treatment are reported.
Time frame: Baseline (Day 1) to Week 24
Population: The intent-to-treat (ITT) population was defined as all randomized participants. The ITT population was the primary analysis population for all efficacy analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pirfenidone | Time to First Investigator-reported Acute Exacerbations | NA Weeks |
| Placebo | Time to First Investigator-reported Acute Exacerbations | NA Weeks |
p-value: 0.787195% CI: [0.26, 2.78]Log Rank