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

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Interstitial Lung Disease
Interventions	Drug: Pirfenidone Other: Placebo controlled
Enrollment	40

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description	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.	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.
Period Title: Overall Study
Started	27	13
Completed ^[1]	27	13
Not Completed	0	0
[1] The study was terminated prematurely in December 2020 following the randomization of 40 patients due to the ongoing impacts of the COVID-19 pandemic.

Baseline Characteristics

Arm/Group Title		Pirfenidone 2403 mg/d	Placebo	Total
Arm/Group Description		Subjects will be randomized in a 2:...	The placebo will be visually simila...	Total of all reporting groups
Arm/Group Description		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.	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 of all reporting groups
Overall Number of Baseline Participants		27	13	40
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	27 participants	13 participants	40 participants
		67.4 (6.5)	66.5 (3.6)	67.1 (4.5)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	27 participants	13 participants	40 participants
	Female	15 55.6%	8 61.5%	23 57.5%
	Male	12 44.4%	5 38.5%	17 42.5%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	27 participants	13 participants	40 participants
Non-hispanic White		25	12	37
Hispanic/Latino		2	1	3
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	27 participants	13 participants	40 participants
United States		27	13	40
Former smoker Measure Type: Number Unit of measure: Participants
	Number Analyzed	27 participants	13 participants	40 participants
		14	7	21

Outcome Measures

1.Primary Outcome


Title	Mean Change From Baseline to Week 52 in Percent Predicted FVC.
Description	The primary efficacy analysis will estimate the mean rank change in pe...
Description	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.
Time Frame	Up to 52 weeks.

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description:	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description:	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.	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 Number of Participants Analyzed	27	13
Mean (Standard Deviation) Unit of Measure: percent predicted
	-0.28 (8.09)	0.58 (12.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone 2403 mg/d, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.76
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	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:
Description	a. Relative decline from baseline in ≥10% in FVC and/or DLCO b. ...
Description	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
Time Frame	Up to 52 weeks.

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description:	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description:	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.	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 Number of Participants Analyzed	27	13
Measure Type: Number Unit of Measure: participants
	14	12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone 2403 mg/d, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.264
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Slope of FVC Over Treatment Period.
Description	The slope for the annual rate of FVC decline
Description	The slope for the annual rate of FVC decline
Time Frame	Up to 52 weeks.

Outcome Measure Data

Analysis Population Description

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


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description:	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description:	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.	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 Number of Participants Analyzed	27	13
Mean (Standard Error) Unit of Measure: percent predicted/year
	1.69 (1.57)	-0.34 (2.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone 2403 mg/d, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Slope
	Estimated Value	2.03
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Mean Change in Percent Predicted DLCO
Description	Mean change in percent predicted diffusing capacity for carbon monoxid...
Description	Mean change in percent predicted diffusing capacity for carbon monoxide (DLCO) from baseline to week 52
Time Frame	Up to 52 weeks.

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description:	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description:	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.	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 Number of Participants Analyzed	27	13
Mean (Standard Deviation) Unit of Measure: percent predicted
	1.02 (12.21)	-2.12 (16.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone 2403 mg/d, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.108
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Number of Participants With All-cause Hospitalization
Description	Proportion of patients with all-cause hospitalization
Description	Proportion of patients with all-cause hospitalization
Time Frame	Up to 52 weeks.

Outcome Measure Data

Analysis Population Description

logistic regression


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description:	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description:	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.	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 Number of Participants Analyzed	27	13
Measure Type: Count of Participants Unit of Measure: Participants
	5 18.5%	5 38.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone 2403 mg/d, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.364
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Number of Participant With Hospitalization for a Respiratory Cause
Description	The proportion of patients with hospitalization for a respiratory caus...
Description	The proportion of patients with hospitalization for a respiratory cause
Time Frame	Up to 52 weeks.

Outcome Measure Data

Analysis Population Description

logistic regression


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description:	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description:	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.	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 Number of Participants Analyzed	27	13
Measure Type: Count of Participants Unit of Measure: Participants
	1 3.7%	3 23.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone 2403 mg/d, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.128
	Estimation Comments	[Not Specified]

7.Secondary Outcome


Title	Visual Extent in the Percentage of Lung CT Fibrosis
Description	Mean change from baseline to week 52 in the visual extent of the perce...
Description	Mean change from baseline to week 52 in the visual extent of the percentage of lung CT fibrosis.
Time Frame	Up to 52 weeks.

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description:	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description:	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.	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 Number of Participants Analyzed	27	13
Mean (Standard Deviation) Unit of Measure: percent of fibrosis
	2.22 (4.0)	6.15 (8.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone 2403 mg/d, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.05
	Estimation Comments	[Not Specified]

8.Other Pre-specified Outcome


Title	St. George's Respiratory Questionnaire.
Description	Mean change from baseline in health-related quality of life, measured ...
Description	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.
Time Frame	Up to 52 weeks.

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description:	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description:	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 42-45 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 42-45 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	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 42-45 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 42-45 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Overall Number of Participants Analyzed	27	13
Mean (95% Confidence Interval) Unit of Measure: score on a scale
	0.890 (-3.64 to 5.42)	7.61 (1.08 to 14.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone 2403 mg/d, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.72
	Estimation Comments	[Not Specified]

9.Other Pre-specified Outcome


Title	Living With Pulmonary Fibrosis Health-Related Quality of Life
Description	Mean change from baseline in health-related quality of life, measured ...
Description	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
Time Frame	Up to 52 weeks.

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description:	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description:	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 42-45 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 42-45 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.	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 42-45 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 42-45 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Overall Number of Participants Analyzed	27	13
Mean (95% Confidence Interval) Unit of Measure: units on a scale
Symptoms	2.99 (-2.91 to 8.9)	11.8 (3.27 to 20.3)
Dyspnea	1.33 (-4.63 to 7.28)	15.6 (7.04 to 24.2)
Energy	2.10 (-5.60 to 9.80)	6.28 (-4.82 to 17.4)
Impact	-3.44 (-9.97 to 3.09)	1.48 (-7.93 to 10.9)
Cough	5.56 (-3.01 to 14.1)	5.71 (-6.64 to 18.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone 2403 mg/d, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.92
	Estimation Comments	[Not Specified]

10.Other Pre-specified Outcome


Title	University of California at San Diego Shortness-of-Breath Questionnaire Score.
Description	Mean change from Baseline to Week 52 in dyspnea as measured by the Uni...
Description	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.
Time Frame	Up to 52 weeks.

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description:	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description:	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.	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 Number of Participants Analyzed	27	13
Mean (95% Confidence Interval) Unit of Measure: score on a scale
	2.06 (-1.10 to 5.22)	4.11 (-0.834 to 9.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone 2403 mg/d, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.92
	Estimation Comments	[Not Specified]

11.Other Pre-specified Outcome


Title	Data-driven Texture-based Quantitative Analysis of the Percent of Lung CT Fibrosis.
Description	The extent of the percentage of lung fibrosis computed by data-driven ...
Description	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.
Time Frame	Up to 52 weeks.

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description:	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description:	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.	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 Number of Participants Analyzed	27	13
Mean (95% Confidence Interval) Unit of Measure: percent of fibrosis
	2.06 (-1.10 to 5.22)	4.11 (-0.834 to 9.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone 2403 mg/d, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.05
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	52 weeks
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Pirfenidone 2403 mg/d	Placebo
Arm/Group Description	Subjects will be randomized in a 2:...	The placebo will be visually simila...
Arm/Group Description	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.	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.
All-Cause Mortality
	Pirfenidone 2403 mg/d	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/27 (0.00%)	1/13 (7.69%)
Serious Adverse Events Serious Adverse Events
	Pirfenidone 2403 mg/d	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/27 (0.00%)	0/13 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Pirfenidone 2403 mg/d	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	27/27 (100.00%)	13/13 (100.00%)
Gastrointestinal disorders
Nausea ^† 1	10/27 (37.04%)	5/13 (38.46%)
Vomiting ^† 1	5/27 (18.52%)	1/13 (7.69%)
Diarrhea ^† 1	4/27 (14.81%)	4/13 (30.77%)
Dyspepsia ^† 1	4/27 (14.81%)	4/13 (30.77%)
Gastroesophageal reflux ^† 1	9/27 (33.33%)	2/13 (15.38%)
Constipation ^† 1	1/27 (3.70%)	1/13 (7.69%)
Infections and infestations
Upper respiratory tract infection ^† 1	6/27 (22.22%)	5/13 (38.46%)
Nervous system disorders
Insomnia ^† 1	3/27 (11.11%)	2/13 (15.38%)
Fatigue ^† 1	7/27 (25.93%)	4/13 (30.77%)
Headache ^† 1	3/27 (11.11%)	1/13 (7.69%)
Dizziness ^† 1	5/27 (18.52%)	1/13 (7.69%)
Respiratory, thoracic and mediastinal disorders
Bronchitis ^† 1	3/27 (11.11%)	2/13 (15.38%)
Nasopharyngitis ^† 1	4/27 (14.81%)	3/13 (23.08%)
Skin and subcutaneous tissue disorders
Rash ^† 1	6/27 (22.22%)	2/13 (15.38%)
Pruritus ^† 1	2/27 (7.41%)	0/13 (0.00%)
1 Term from vocabulary, MedDRA (21.0) † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Dr. Evans Fernández
Organization:	National Jewish Health
Phone:	303-388-4461
EMail:	fernandezevans@njheallth.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fernandez Perez ER, Crooks JL, Swigris JJ, Solomon JJ, Mohning MP, Huie TJ, Koslow M, Lynch DA, Groshong SD, Fier K. Design and rationale of a randomised, double-blind trial of the efficacy and safety of pirfenidone in patients with fibrotic hypersensitivity pneumonitis. ERJ Open Res. 2021 Jun 7;7(2):00054-2021. doi: 10.1183/23120541.00054-2021. eCollection 2021 Apr.

Layout table for additonal information

Responsible Party:	Evans Fernandez Perez, National Jewish Health
ClinicalTrials.gov Identifier:	NCT02958917
Other Study ID Numbers:	HS-3034
First Submitted:	October 31, 2016
First Posted:	November 8, 2016
Results First Submitted:	September 27, 2022
Results First Posted:	January 9, 2023
Last Update Posted:	January 9, 2023