Trial Outcomes & Findings for Study of Efficacy and Safety of Pirfenidone in Patients With Fibrotic Hypersensitivity Pneumonitis (NCT NCT02958917)

NCT ID: NCT02958917

Last Updated: 2023-01-09

Results Overview

The primary efficacy analysis will estimate the mean rank change in percent predicted FVC from Baseline to Week 52. Data will be analyzed using a rank linear regression model with the rank change in percent predicted FVC from Baseline to Week 52 as the outcome variable and rank Baseline percent predicted FVC and HP therapy (placebo or pirfenidone) and concomitant immunosuppressive therapy as covariates. The treatment effect will be tested using the Wald test. The primary efficacy analysis will be tested at an alpha level of 0.05. Missing data due to reasons other than death will be replaced with imputed values using the MICE method (multiple imputations via chained equation). Subjects with missing assessments due to death will be ranked worse than those who remain alive. Subjects who die will be ranked according to the time until death, with the shortest time until death as the worst rank.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: Up to 52 weeks.
• Results posted on: 2023-01-09

Participant Flow

Participant milestones

Measure	Pirfenidone 2403 mg/d Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Overall Study STARTED	27	13
Overall Study COMPLETED	27	13
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Efficacy and Safety of Pirfenidone in Patients With Fibrotic Hypersensitivity Pneumonitis

Baseline characteristics by cohort

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Total n=40 Participants Total of all reporting groups
Age, Continuous	67.4 years STANDARD_DEVIATION 6.5 • n=5 Participants	66.5 years STANDARD_DEVIATION 3.6 • n=7 Participants	67.1 years STANDARD_DEVIATION 4.5 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	8 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Non-hispanic White	25 participants n=5 Participants	12 participants n=7 Participants	37 participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants	13 participants n=7 Participants	40 participants n=5 Participants
Former smoker	14 participants n=5 Participants	7 participants n=7 Participants	21 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 52 weeks.

Population: The primary efficacy analysis will be analyzed using a rank linear regression model with the rank change in %FVC from Baseline to Week 52 as the outcome variable and rank Baseline %FVC and HP therapy (placebo or pirfenidone) and concomitant immunosuppressive therapy as covariates. The treatment effect will be tested using the Wald test at an alpha level of 0.05.

The primary efficacy analysis will estimate the mean rank change in percent predicted FVC from Baseline to Week 52. Data will be analyzed using a rank linear regression model with the rank change in percent predicted FVC from Baseline to Week 52 as the outcome variable and rank Baseline percent predicted FVC and HP therapy (placebo or pirfenidone) and concomitant immunosuppressive therapy as covariates. The treatment effect will be tested using the Wald test.

The primary efficacy analysis will be tested at an alpha level of 0.05. Missing data due to reasons other than death will be replaced with imputed values using the MICE method (multiple imputations via chained equation).

Subjects with missing assessments due to death will be ranked worse than those who remain alive. Subjects who die will be ranked according to the time until death, with the shortest time until death as the worst rank.

Outcome measures

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Mean Change From Baseline to Week 52 in Percent Predicted FVC.	-0.28 percent predicted Standard Deviation 8.09	0.58 percent predicted Standard Deviation 12.42

SECONDARY outcome

Timeframe: Up to 52 weeks.

Population: Progression-free survival was compared between the pirfenidone and placebo groups using the log-rank test. A proportional hazards model was used to estimate the hazard ratio with 95% confidence intervals.

a. Relative decline from baseline in ≥10% in FVC and/or DLCO b. Acute exacerbation of FHP defined as acute respiratory declined leading to hospitalization or ER or Urgent care evaluation; or evidence of all of the following criteria within a 4-week period in the outpatient setting: i. Increase from baseline FIO2 ≥1 L O2. ii. Clinically significant worsening of dyspnea and/or cough. iii. New, superimposed ground-glass opacities or consolidation or new alveolar opacities on chest x-ray or CT.

c. A decrease from baseline of at least 50 meters in 6mw distance. d. Change in background therapy (need for a new course of PO or IV steroids or for the patient receiving maintenance prednisone, as a need to increase the dose by 10 mg or more; and/or addition of cyclophosphamide, azathioprine, mycophenolate mofetil, or mycophenolic acid).

e. Death

Outcome measures

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Number of Participants With Progression-free Survival (PFS) Defined as the Time From Study Treatment Randomization to the First Occurrence of Any of the Following Events:	14 participants	12 participants

SECONDARY outcome

Timeframe: Up to 52 weeks.

Population: The slope for the annual rate of FVC% decline will be analyzed using a random coefficient regression model with treatment and baseline FVC% as covariates

The slope for the annual rate of FVC decline

Outcome measures

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Slope of FVC Over Treatment Period.	1.69 percent predicted/year Standard Error 1.57	-0.34 percent predicted/year Standard Error 2.07

SECONDARY outcome

Timeframe: Up to 52 weeks.

Population: The diffusing capacity for carbon monoxide (DLCO) was analyzed using a rank linear regression model with the rank change in DLCO% predicted from baseline to week 52 as the outcome variable and rank baseline percent predicted DLCO and FHP therapy as covariates.

Mean change in percent predicted diffusing capacity for carbon monoxide (DLCO) from baseline to week 52

Outcome measures

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Mean Change in Percent Predicted DLCO	1.02 percent predicted Standard Deviation 12.21	-2.12 percent predicted Standard Deviation 16.41

SECONDARY outcome

Timeframe: Up to 52 weeks.

Population: logistic regression

Proportion of patients with all-cause hospitalization

Outcome measures

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Number of Participants With All-cause Hospitalization	5 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 52 weeks.

Population: logistic regression

The proportion of patients with hospitalization for a respiratory cause

Outcome measures

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Number of Participant With Hospitalization for a Respiratory Cause	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 52 weeks.

Population: The visual assessment of the extent of the percentage of lung CT fibrosis will be compared between the pirfenidone and placebo groups using logistic regression accounting for possible over- or under-dispersion in the outcome. This is not a range but the percentage extent or percent amount of fibrosis visually identified by a radiologist on the lung CT.

Mean change from baseline to week 52 in the visual extent of the percentage of lung CT fibrosis.

Outcome measures

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Visual Extent in the Percentage of Lung CT Fibrosis	2.22 percent of fibrosis Standard Deviation 4.0	6.15 percent of fibrosis Standard Deviation 8.45

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 52 weeks.

Population: SGRQ baseline to 52 weeks was analyzed using a linear regression model with a separate intercept for each subject, a dichotomous time-point effect, and a multiplicative interaction between time-point and treatment.

Mean change from baseline in health-related quality of life, measured by SGRQ The total score ranges from 0 to 100, with higher scores indicating worse health-related quality of life.

Outcome measures

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
St. George's Respiratory Questionnaire.	0.890 score on a scale Interval -3.64 to 5.42	7.61 score on a scale Interval 1.08 to 14.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 52 weeks.

Population: L-PF baseline to 52 weeks was analyzed using a linear regression model with a separate intercept for each subject, a dichotomous time-point effect, and a multiplicative interaction between time-point and treatment.

Mean change from baseline in health-related quality of life, measured by the Living with pulmonary fibrosis questionnaire includes 5 subscores.

Scores range for each of the 5 subscores go from 0 to 100, with higher scores indicating greater impairment

Outcome measures

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Living With Pulmonary Fibrosis Health-Related Quality of Life Energy	2.10 units on a scale Interval -5.6 to 9.8	6.28 units on a scale Interval -4.82 to 17.4
Living With Pulmonary Fibrosis Health-Related Quality of Life Impact	-3.44 units on a scale Interval -9.97 to 3.09	1.48 units on a scale Interval -7.93 to 10.9
Living With Pulmonary Fibrosis Health-Related Quality of Life Cough	5.56 units on a scale Interval -3.01 to 14.1	5.71 units on a scale Interval -6.64 to 18.1
Living With Pulmonary Fibrosis Health-Related Quality of Life Symptoms	2.99 units on a scale Interval -2.91 to 8.9	11.8 units on a scale Interval 3.27 to 20.3
Living With Pulmonary Fibrosis Health-Related Quality of Life Dyspnea	1.33 units on a scale Interval -4.63 to 7.28	15.6 units on a scale Interval 7.04 to 24.2

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 52 weeks.

Population: UCSD-SOBQ baseline to 52 weeks was analyzed using a linear regression model with a separate intercept for each subject, a dichotomous time-point effect, and a multiplicative interaction between time-point and treatment.

Mean change from Baseline to Week 52 in dyspnea as measured by the University of California at San Diego Shortness-of-Breath Questionnaire score.

Scores range from 0 to 120, with higher scores indicating greater breathlessness.

Outcome measures

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
University of California at San Diego Shortness-of-Breath Questionnaire Score.	2.06 score on a scale Interval -1.1 to 5.22	4.11 score on a scale Interval -0.834 to 9.05

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 52 weeks.

Population: a linear regression model with a separate intercept for each subject, a dichotomous time-point effect, and a multiplicative interaction between time-point and treatment.

The extent of the percentage of lung fibrosis computed by data-driven texture-based quantitative analysis. The data-driven texture-based quantitative analysis is computed as the percentage of the total lung with fibrosis.

Outcome measures

Measure	Pirfenidone 2403 mg/d n=27 Participants Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 Participants The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Data-driven Texture-based Quantitative Analysis of the Percent of Lung CT Fibrosis.	2.06 percent of fibrosis Interval -1.1 to 5.22	4.11 percent of fibrosis Interval -0.834 to 9.05

Adverse Events

Pirfenidone 2403 mg/d

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Pirfenidone 2403 mg/d n=27 participants at risk Subjects will be randomized in a 2:1 ratio to receive either pirfenidone 2403 mg/d or a placebo equivalent. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	Placebo n=13 participants at risk The placebo will be visually similar to pirfenidone. Pirfenidone: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks. Placebo controlled: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 40 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Gastrointestinal disorders Nausea	37.0% 10/27 • 52 weeks	38.5% 5/13 • 52 weeks
Gastrointestinal disorders Vomiting	18.5% 5/27 • 52 weeks	7.7% 1/13 • 52 weeks
Gastrointestinal disorders Diarrhea	14.8% 4/27 • 52 weeks	30.8% 4/13 • 52 weeks
Gastrointestinal disorders Dyspepsia	14.8% 4/27 • 52 weeks	30.8% 4/13 • 52 weeks
Gastrointestinal disorders Gastroesophageal reflux	33.3% 9/27 • 52 weeks	15.4% 2/13 • 52 weeks
Gastrointestinal disorders Constipation	3.7% 1/27 • 52 weeks	7.7% 1/13 • 52 weeks
Nervous system disorders Insomnia	11.1% 3/27 • 52 weeks	15.4% 2/13 • 52 weeks
Nervous system disorders Fatigue	25.9% 7/27 • 52 weeks	30.8% 4/13 • 52 weeks
Skin and subcutaneous tissue disorders Rash	22.2% 6/27 • 52 weeks	15.4% 2/13 • 52 weeks
Infections and infestations Upper respiratory tract infection	22.2% 6/27 • 52 weeks	38.5% 5/13 • 52 weeks
Respiratory, thoracic and mediastinal disorders Bronchitis	11.1% 3/27 • 52 weeks	15.4% 2/13 • 52 weeks
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	14.8% 4/27 • 52 weeks	23.1% 3/13 • 52 weeks
Nervous system disorders Headache	11.1% 3/27 • 52 weeks	7.7% 1/13 • 52 weeks
Nervous system disorders Dizziness	18.5% 5/27 • 52 weeks	7.7% 1/13 • 52 weeks
Skin and subcutaneous tissue disorders Pruritus	7.4% 2/27 • 52 weeks	0.00% 0/13 • 52 weeks

Additional Information

Dr. Evans Fernández

National Jewish Health

Phone: 303-388-4461

Email: fernandezevans@njheallth.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place