Phase ll Study of Pirfenidone in Patients With RAILD (TRAIL1)

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02808871
• Collaborator: (none)
• Enrollment: 123
• Locations: 33
• Arms: 2
• Actual Duration (Months): 48
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to to assess the safety and tolerability of pirfenidone 2403 mg/day for the treatment of RA-associated interstitial lung disease.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis Interstitial Lung Disease	Drug: Pirfenidone; Drug: Placebo	Phase 2

Detailed Description

This is a phase 2, randomized, double blind, placebo controlled trial of pirfenidone for the treatment of RA associated interstitial lung disease. Approximately 270 subjects will be randomized to receive Pirfenidone 2403 mg per day or placebo in a 1:1 ratio. The primary outcome of this study is to assess the efficacy of pirfenidone 2403 mg/day versus placebo in patients with RA associated interstitial lung disease, as defined by progression free survival over the 52 weeks of treatment. Patients will receive blinded study treatment from the time of randomization until the Week 52 Visit.

Eligible patients aged 18 to 85 years must meet 2010 ACR/EULAR criteria for RA (Aletaha, Neogi et al. 2010) as well as RA-associated ILD, as determined by imaging and, when available, lung biopsy. Patients will be required to have a % predicted FVC ≥40 and % predicted DLCO or TLCO ≥30 at screening.

The dose of study treatment will be titrated over 14 days. Patients will receive a telephone assessment at Weeks 1 and 2, and visit the clinic at Weeks 4, 8, 13, 19, 26, 39, and 52. Subjects will have a follow up phone call 28 days after completion of the study drug. Patients should complete a compliance diary between visits. If patients discontinue study treatment for any reason before the end of the study, they should continue with all scheduled study procedures through Week 52. If subjects are unable to complete the study visits as scheduled, all efforts should be made to complete an early termination visit.

The primary outcome variable of this study will be progression free survival, defined as progression free from decline in FVC of 10% or greater during the 52 week study period.

More information can be found at www.ralung.org.

Study Design

• Study Type: Interventional
• Actual Enrollment: 123 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of Safety, Tolerability and Efficacy of Pirfenidone in Patients With Rheumatoid Arthritis Interstitial Lung Disease (TRAIL1)
• Actual Study Start Date: Apr 7, 2017
• Actual Primary Completion Date: Apr 7, 2021
• Actual Study Completion Date: Apr 7, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pirfenidone Pirfenidone 2403 mg/d for 52 weeks	Drug: Pirfenidone; Pirfenidone three times daily (2403 mg) for 52 weeks; Other Names: Esbriet
Placebo Comparator: Placebo Placebo for 52 weeks	Drug: Placebo; Placebo three times daily for 52 weeks

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Developed Any Element of the Composite Endpoint [52 weeks]

   Number of participants who developed any element of the composite endpoint of decline in percent predicted FVC of 10% or greater or death.

Secondary Outcome Measures

1. Number of Participants With FVC Decline From Baseline of 10% or Greater [52 weeks]

   Number of participants with decline from baseline in percent predicted FVC of 10% or greater during the study period.

2. Number of Participants With Progressive Disease [52 weeks]

   Number of participants with progressive disease as defined by OMERACT: FVC% relative decline of >=10% or FVC% change in >=5< 10% and >=15% diffusing capacity (DLCO)

3. Change in Absolute Value FVC Over the 52 Week Study Period [52 weeks]

   Change from baseline to end of study in absolute value of FVC over the 52 week study period

4. Change in % Predicted FVC From Baseline to End of Study Over the 52 Week Study Period [52 weeks]

   Change from baseline to end of study of percent predicted FVC over the 52 week study period

5. Time to Composite of Decline in FVC or Death [52 weeks]

   Time to decline of 10% or greater in percent predicted FVC or death while on study

6. Change in PRO of Dyspnea [52 weeks]

   Change from Baseline to end of study in dyspnea, as measured by the Dyspnea 12 questionnaire - Total scores range from 0 to 36, with higher scores corresponding to greater severity.

7. All-cause Mortality [52 weeks]

   Number of participants experiencing mortality due to all causes

8. All Cause Hospitalization [52 weeks]

   Number of participants requiring hospitalization for any cause

9. Hospitalization for Respiratory Cause [52 weeks]

   Number of participants requiring hospitalization for respiratory cause

10. Acute Exacerbations Requiring Hospitalization [52 weeks]

    Number of participants experiencing acute exacerbation requiring hospitalization

11. Treatment-emergent Adverse Events (AEs) [52 weeks]

    Number of participants with treatment-emergent adverse events (AEs)

12. Treatment-emergent Serious Adverse Events (SAEs) [52 weeks]

    Number of participants with treatment-emergent serious adverse events (SAEs) in the as treated population

13. Treatment-emergent/Treatment-related AEs [52 weeks]

    Number of participants with treatment-emergent/treatment-related AEs

14. Treatment-emergent/Treatment-related SAEs [52 weeks]

    Number of participants with treatment-emergent/treatment-related SAEs

15. AEs Leading to Early Discontinuation of Study Treatment [52 weeks]

    Number of participants with AEs leading to early discontinuation of study treatment

16. Treatment-emergent Death or Transplant [52 weeks]

    Number of participants who experienced treatment-emergent death or transplant

17. Treatment-emergent RA-ILD-related Mortality [52 weeks]

    Number of participants who experienced treatment-emergent RA-ILD-related mortality

Other Outcome Measures

1. Disease Activity Score (DAS) [52 weeks]

   Change from Baseline to end of study in Disease Activity Score (DAS)

2. RAPID3 Score [52 weeks]

   Change from baseline to end of study in Routine Assessment of Patient Index Data 3 (RAPID3) score

3. Erythrocyte Sedimentation Rate (ESR) [52 weeks]

   Change from Baseline to end of study in Erythrocyte Sedimentation Rate (ESR)

4. CRP [52 weeks]

   Change from Baseline to end of study in C-Reactive Protein (CRP) 5. Candidate

5. Biomarker Expression [52 weeks]

   Candidate biomarker expression in the peripheral blood of patients with RA-ILD over the 52 weeks of treatment

6. HRCT Parameters [52 weeks]

   Changes from Baseline to end of study in high resolution computed tomography (HRCT) parameters evaluated by quantitative functional imaging

7. SGRQ [52 weeks]

   Changes from Baseline to Week 13, 26, 39 and final visit in the St. George's Respiratory Questionnaire (SGRQ)

8. Dyspnea 12 [52 weeks]

   Changes from Baseline to Week 13, 26, 39 and final visit in Dyspnea 12 questionnaire

9. LCQ [52 weeks]

   Changes from Baseline to Week 13, 26, 39 and final visit in Leicester Cough Questionnaire (LCQ)

10. Patient Global Assessment [52 weeks]

    Changes from Baseline to Week 13, 26, 39 and final visit in the Patient global assessment

11. Health Assessment Questionnaire [52 weeks]

    Changes from Baseline to Week 13, 26, 39 and final visit in the Health assessment questionnaire

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Patients must fulfill all of the following criteria to be eligible for enrollment in the study:

1. Age 18 through 85 years, inclusive, at Screening

2. Probable or definite diagnosis of RA according to revised 2010 ACR/EULAR criteria, without evidence or suspicion of an alternative diagnosis that may contribute to their interstitial lung disease.

3. Diagnosis of ILD

4. supported by clinically indicated HRCT, and when available, surgical lung biopsy (SLB), prior to Screening, and

5. presence of fibrotic abnormality affecting more than 10% of the lung parenchyma, with or without traction bronchiectasis or honeycombing, on screening and confirmed by adjudicated HRCT prior to Baseline

6. No features supporting an alternative diagnosis on transbronchial biopsy, or SLB, if performed prior to Screening

7. Attainment of the following centralized spirometry criteria (based on local spirometry on standardized equipment and centralized quality controlled):

8. percent predicted FVC ≥ 40% at Screening

9. change in pre-bronchodilator FVC (measured in liters) between Visit 1 (Screening) and Visit 2 (Randomization) must be a <10% relative difference, calculated as: 100% * [absolute value (Visit 1 FVC - Visit 2 FVC) / Visit 1 FVC]

10. percent predicted DLCO or TLCO ≥25 % at Screening

11. Screening (Visit 1) pre-bronchodilator(BD) and Post-BD spirometry meets ATS quality criteria as determined by a central reviewer

12. Baseline (Visit 2) Pre-BD spirometry meets ATS quality criteria as determined by the site Investigator or the central reviewer

13. Able to understand and sign a written informed consent form.

14. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year, during the 52 week treatment period and for at least 118 days after the last dose of study drug.

15. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).

16. Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, established and proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

17. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

18. For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:

19. With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 118 days after the last dose of study drug.

20. Men must refrain from donating sperm during this same period.

PARTICIPANT EXCLUSION CRITERIA

1. Not a suitable candidate for enrollment or unlikely to comply with the requirements of this study, in the opinion of the investigator

2. Cigarette smoking or vaping within 3 months of Screening or unwilling to avoid tobacco products throughout the study

3. History of clinically significant environmental exposure known to cause pulmonary fibrosis (PF), including but not limited to drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds

4. Concurrent presence of the following conditions:

5. Other interstitial lung disease, related to but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, or bronchiolitis obliterans organizing pneumonia

6. Medical history including Human Immunodeficiency Virus (HIV)

7. Medical history of viral hepatitis (positive Hep A antibody in the absence of elevated liver enzymes is not an exclusion)

8. Concurrent presence of other pleuropulmonary manifestations of RA, including but not limited to rheumatoid nodular disease of the lung, pleuritis/pleural thickening, and obliterative bronchiolitis

9. Post-bronchodilator FEV1/FVC <0.65 at Screening

10. Presence of pleural effusion occupying more than 20% of the hemithorax on Screening HRCT

11. Clinical diagnosis of a second connective tissue disease or overlap syndrome (including but not limited to scleroderma, sjogren's, polymyositis/dermatomyositis, systemic lupus erythematosus but excluding Raynaud's phenomena)

12. Coexistent clinically significant COPD/emphysema or asthma in the opinion of the site principal investigator

13. Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis. The infection should be resolved per PI assessment prior to enrollment. Any use of antibiotics must be completed 2weeks prior to the screening visit. Note that prophylactic antibiotics are not contraindicated or exclusionary

14. Any history of malignancy diagnosed within 5 years of screening, other than basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or low grade cervical carcinoma, and/or low grade prostate cancer.

Criteria for low grade prostate cancer:

• Patients with suspicion for prostate cancer based on PSA and/or DRE should have been evaluated by urology

• Patients with NCCN very low risk prostate cancer (∙ T1c and Grade Group 1 (Gleason 6) and PSA <10 ng/mL and Fewer than 3 prostate biopsy fragments/cores positive, ≤50% cancer in each fragment/coreg and ∙ PSA density <0.15 ng/mL/g) can be monitored without intervention and enrolled in study.

• Patients with NCCN low risk prostate cancer can be monitored on a case by case basis (T1-T2a and Grade Group 1 (Gleason 6) and ∙ PSA <10 ng/mL) and enrolled in study.

• All other patients should be excluded.

1. History of LFT abnormalities as outlined below, or imaging, laboratory or other clinical information suggesting liver dysfunction, advanced liver disease or cirrhosis. Evidence of hepatic impairment that in the opinion of the investigator could interfere with drug metabolism or increase the risk of the known hepatotoxicity of study drug.

Any of the following liver function abnormalities:

1. Total bilirubin above the upper limit of normal (ULN), excluding patients with Gilbert's syndrome;

2. Aspartate or alanine aminotransferase (AST/SGOT or AST/SGPT) > 3 X ULN;

3. Alkaline phosphatase > 2.5 X ULN.

4. History of end-stage renal disease requiring dialysis

5. History of unstable or deteriorating cardiac disease, or unstable cardiac arrhythmia or arrhythmia requiring modification of drug therapy, myocardial infarction within the previous year, heart failure requiring hospitalization.

6. Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone

7. History of alcohol or substance abuse in the past 2 years, at the time of Screening

8. Family or personal history of long QT syndrome

9. Any of the following test criteria above specified limits:

10. Estimated glomerular filtration rate <30 mL/min/1.73m2

11. ECG with a QTc interval >500 msec at Screening

12. Prior use of pirfenidone or known hypersensitivity to any of the components of study treatment

13. Use of any of the following therapies within 28 days before Screening and during participation in the study:

14. Investigational therapy, defined as any drug that has not been approved for marketing for any indication in the country of the participating site

15. Potent inhibitors of CYP1A2(e.g. fluvoxamine, enoxacin)

16. Potent inducers of CYP1A2.

17. Sildenafil (daily use). Note: intermittent use for erectile dysfunction is allowed

18. Introduction and/or modification of dose of corticosteroids or any cytotoxic, immunosuppressive, or cytokine modulating or receptor antagonist agent for the management of pulmonary manifestations of RA, within 3 months of screening, is an exclusion criterion for enrollment, with the exception of dose modification of systemic corticosteroids that are maintained at or below 20 mg prednisone daily or the equivalent.

However, introduction and/or modification of dose of corticosteroids or any cytotoxic, immunosuppressive, or cytokine modulating or receptor antagonist agent for the management of extrapulmonary manifestations of RA is not an exclusion criterion for enrollment.

1. Any use of an approved anti-fibrotic medication within 28 days of screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Site at Birmingham	Birmingham	Alabama	United States	35294
2	University of California San Francisco	San Francisco	California	United States	94143
3	National Jewish Health	Denver	Colorado	United States	80206
4	University of Miami	Miami	Florida	United States	33136
5	Tulane Medical Center	New Orleans	Louisiana	United States	70112
6	John Hopkins Medicine	Baltimore	Maryland	United States	21224
7	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
8	University of Michigan	Ann Arbor	Michigan	United States	48109
9	Mayo Clinic	Rochester	Minnesota	United States	55905
10	Weill Cornell Medicine	New York	New York	United States	10065
11	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
12	University of Utah Health Care	Salt Lake City	Utah	United States	84132
13	University of Washington	Seattle	Washington	United States	98195
14	Royal Brompton	Brisbane	Queensland	Australia	4032
15	Royal Prince Alfred Hospital	Camperdown	Sydney	Australia	NSW 2050
16	Melbourne Alfred Hospital	Melbourne	Victoria	Australia	3004
17	The Prince Charles Hospital	Camperdown		Australia	2050
18	University of Calgary Cummings School of Medicine	Calgary	Alberta	Canada	T3M 1M4
19	St. Paul's Hospital - Providence Health Care	Vancouver	British Columbia	Canada	V6Z1Y6
20	St. Joseph's Healthcare	Hamilton	Ontario	Canada	L8N 4A6
21	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
22	North Bristol NHS Trust Headquarters, Southmead Hospital	Bristol		United Kingdom	BS10 5NB
23	Papworth Hospital NHS Foundation Trust	Cambridge		United Kingdom	CB23 3RE
24	Royal Devon and Exeter NHS Foundation	Exeter		United Kingdom	EX2 5DW
25	Leeds Teaching Hospitals NHS Trust	Leeds		United Kingdom	LS9 7TF
26	University Hospitals of Leicester NHS Foundation Trust	Leicester		United Kingdom	LE3 9QP
27	Aintree University Hospitals NHS Foundation Trust	Liverpool		United Kingdom	L9 7AL
28	Royal Brompton and Harefield NHS Foundation Trust	London		United Kingdom	SW3 6NP
29	Manchester University NHS Foundation Trust (South) Wythenshawe Hospita	Manchester		United Kingdom	M23 9LT
30	Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne		United Kingdom	NE1 4LP
31	Norfolk and Norwich University Hospitals NHS Foundation Trust	Norwich		United Kingdom	NR4 7UY
32	Oxford University Hospitals NHS Foundation Trust	Oxford		United Kingdom	OX3 7LE
33	University Hospital Southampton NHS Foundation Trust	Southhampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

• Principal Investigator: Ivan O. Rosas, M.D., Brigham and Women's Hospital

Study Documents (Full-Text)

• Study Protocol - Oct 13, 2020
• Statistical Analysis Plan - May 10, 2021

More Information

Publications

None provided.

• Responsible Party: Hilary J. Goldberg, M.D., Attending Physician, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT02808871
• Other Study ID Numbers: 2017p000062
• First Posted: Jun 22, 2016
• Last Update Posted: Aug 16, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Hilary J. Goldberg, M.D., Attending Physician, Brigham and Women's Hospital: TRAIL1; TRAIL; Pirfenidone
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Lung Diseases; Lung Diseases, Interstitial; Pirfenidone

Study Results

Participant Flow

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks Pirfenidone: Pirfenidone three times daily (2403 mg) for 52 weeks	Placebo for 52 weeks Placebo: Placebo three times daily for 52 weeks
Period Title: Overall Study
STARTED	63	60
COMPLETED	52	51
NOT COMPLETED	11	9

Baseline Characteristics

Arm/Group Title	Pirfenidone	Placebo	Total
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks	Total of all reporting groups
Overall Participants	63	60	123
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	27 42.9%	18 30%	45 36.6%
>=65 years	36 57.1%	42 70%	78 63.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.6 (8.2)	68.1 (9.1)	67.3 (8.6)
Sex: Female, Male (Count of Participants)
Female	25 39.7%	21 35%	46 37.4%
Male	38 60.3%	39 65%	77 62.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.6%	0 0%	1 0.8%
Asian	4 6.3%	0 0%	4 3.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 3.2%	1 1.7%	3 2.4%
White	56 88.9%	56 93.3%	112 91.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	3 5%	3 2.4%
Region of Enrollment (participants) [Number]
Canada	6 9.5%	5 8.3%	11 8.9%
United States	25 39.7%	23 38.3%	48 39%
United Kingdom	27 42.9%	27 45%	54 43.9%
Australia	5 7.9%	5 8.3%	10 8.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Developed Any Element of the Composite Endpoint
Description	Number of participants who developed any element of the composite endpoint of decline in percent predicted FVC of 10% or greater or death.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	63	60
Count of Participants [Participants]	7 11.1%	9 15%

2. Secondary Outcome

Title	Number of Participants With FVC Decline From Baseline of 10% or Greater
Description	Number of participants with decline from baseline in percent predicted FVC of 10% or greater during the study period.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	63	60
Count of Participants [Participants]	5 7.9%	7 11.7%

3. Secondary Outcome

Title	Number of Participants With Progressive Disease
Description	Number of participants with progressive disease as defined by OMERACT: FVC% relative decline of >=10% or FVC% change in >=5< 10% and >=15% diffusing capacity (DLCO)
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	63	60
Count of Participants [Participants]	16 25.4%	19 31.7%

4. Secondary Outcome

Title	Change in Absolute Value FVC Over the 52 Week Study Period
Description	Change from baseline to end of study in absolute value of FVC over the 52 week study period
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	63	60
Mean (Standard Deviation) [ml]	-66 (20)	-146 (20)

5. Secondary Outcome

Title	Change in % Predicted FVC From Baseline to End of Study Over the 52 Week Study Period
Description	Change from baseline to end of study of percent predicted FVC over the 52 week study period
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	63	60
Mean (Standard Deviation) [% predicted]	-1.02 (0.51)	-3.21 (0.52)

6. Secondary Outcome

Title	Time to Composite of Decline in FVC or Death
Description	Time to decline of 10% or greater in percent predicted FVC or death while on study
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	63	60
Mean (Standard Error) [days]	349.5 (7.2)	339.9 (10.2)

7. Secondary Outcome

Title	Change in PRO of Dyspnea
Description	Change from Baseline to end of study in dyspnea, as measured by the Dyspnea 12 questionnaire - Total scores range from 0 to 36, with higher scores corresponding to greater severity.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	63	60
Mean (Standard Deviation) [score]	0.45 (0.71)	1.37 (0.72)

8. Secondary Outcome

Title	All-cause Mortality
Description	Number of participants experiencing mortality due to all causes
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	63	60
Count of Participants [Participants]	2 3.2%	3 5%

9. Secondary Outcome

Title	All Cause Hospitalization
Description	Number of participants requiring hospitalization for any cause
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Received pirfenidone	Received placebo
Measure Participants	63	60
Count of Participants [Participants]	7 11.1%	7 11.7%

10. Secondary Outcome

Title	Hospitalization for Respiratory Cause
Description	Number of participants requiring hospitalization for respiratory cause
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Received pirfenidone	Received placebo
Measure Participants	63	60
Count of Participants [Participants]	2 3.2%	5 8.3%

11. Secondary Outcome

Title	Acute Exacerbations Requiring Hospitalization
Description	Number of participants experiencing acute exacerbation requiring hospitalization
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	63	60
Count of Participants [Participants]	1 1.6%	2 3.3%

12. Secondary Outcome

Title	Treatment-emergent Adverse Events (AEs)
Description	Number of participants with treatment-emergent adverse events (AEs)
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	62	60
Count of Participants [Participants]	62 98.4%	56 93.3%

13. Secondary Outcome

Title	Treatment-emergent Serious Adverse Events (SAEs)
Description	Number of participants with treatment-emergent serious adverse events (SAEs) in the as treated population
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	62	60
Count of Participants [Participants]	9 14.3%	8 13.3%

14. Secondary Outcome

Title	Treatment-emergent/Treatment-related AEs
Description	Number of participants with treatment-emergent/treatment-related AEs
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	62	60
Count of Participants [Participants]	27 42.9%	18 30%

15. Secondary Outcome

Title	Treatment-emergent/Treatment-related SAEs
Description	Number of participants with treatment-emergent/treatment-related SAEs
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	62	60
Count of Participants [Participants]	1 1.6%	0 0%

16. Secondary Outcome

Title	AEs Leading to Early Discontinuation of Study Treatment
Description	Number of participants with AEs leading to early discontinuation of study treatment
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	62	60
Count of Participants [Participants]	15 23.8%	6 10%

17. Secondary Outcome

Title	Treatment-emergent Death or Transplant
Description	Number of participants who experienced treatment-emergent death or transplant
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	62	60
Count of Participants [Participants]	2 3.2%	4 6.7%

18. Secondary Outcome

Title	Treatment-emergent RA-ILD-related Mortality
Description	Number of participants who experienced treatment-emergent RA-ILD-related mortality
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone	Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks	Placebo for 52 weeks
Measure Participants	62	60
Count of Participants [Participants]	1 1.6%	0 0%

19. Other Pre-specified Outcome

Title	Disease Activity Score (DAS)
Description	Change from Baseline to end of study in Disease Activity Score (DAS)
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

20. Other Pre-specified Outcome

Title	RAPID3 Score
Description	Change from baseline to end of study in Routine Assessment of Patient Index Data 3 (RAPID3) score
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

21. Other Pre-specified Outcome

Title	Erythrocyte Sedimentation Rate (ESR)
Description	Change from Baseline to end of study in Erythrocyte Sedimentation Rate (ESR)
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

22. Other Pre-specified Outcome

Title	CRP
Description	Change from Baseline to end of study in C-Reactive Protein (CRP) 5. Candidate
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

23. Other Pre-specified Outcome

Title	Biomarker Expression
Description	Candidate biomarker expression in the peripheral blood of patients with RA-ILD over the 52 weeks of treatment
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

24. Other Pre-specified Outcome

Title	HRCT Parameters
Description	Changes from Baseline to end of study in high resolution computed tomography (HRCT) parameters evaluated by quantitative functional imaging
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

25. Other Pre-specified Outcome

Title	SGRQ
Description	Changes from Baseline to Week 13, 26, 39 and final visit in the St. George's Respiratory Questionnaire (SGRQ)
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

26. Other Pre-specified Outcome

Title	Dyspnea 12
Description	Changes from Baseline to Week 13, 26, 39 and final visit in Dyspnea 12 questionnaire
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

27. Other Pre-specified Outcome

Title	LCQ
Description	Changes from Baseline to Week 13, 26, 39 and final visit in Leicester Cough Questionnaire (LCQ)
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

28. Other Pre-specified Outcome

Title	Patient Global Assessment
Description	Changes from Baseline to Week 13, 26, 39 and final visit in the Patient global assessment
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

29. Other Pre-specified Outcome

Title	Health Assessment Questionnaire
Description	Changes from Baseline to Week 13, 26, 39 and final visit in the Health assessment questionnaire
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86).
Adverse Event Reporting Description	Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Arm/Group Title	Pirfenidone		Placebo
Arm/Group Description	Pirfenidone 2403 mg/d for 52 weeks		Placebo for 52 weeks
All Cause Mortality
	Pirfenidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/63 (3.2%)		3/60 (5%)
Serious Adverse Events
	Pirfenidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/62 (16.1%)		11/60 (18.3%)
Cardiac disorders
Cardiac	3/62 (4.8%)		0/60 (0%)
Gastrointestinal disorders
Gastrointestinal	1/62 (1.6%)		1/60 (1.7%)
Immune system disorders
Immune System	1/62 (1.6%)		0/60 (0%)
Infections and infestations
Infections and Infestations	3/62 (4.8%)		3/60 (5%)
Musculoskeletal and connective tissue disorders
Musculoskeletal and Connective Tissue	0/62 (0%)		2/60 (3.3%)
Nervous system disorders
Nervous System	0/62 (0%)		2/60 (3.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory, Thoracic and Mediastinal	2/62 (3.2%)		3/60 (5%)
Other (Not Including Serious) Adverse Events
	Pirfenidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	62/62 (100%)		56/60 (93.3%)
Blood and lymphatic system disorders
Blood and Lymphatic System	7/62 (11.3%)		6/60 (10%)
Cardiac disorders
Cardiac	12/62 (19.4%)		9/60 (15%)
Ear and labyrinth disorders
Ear and Labyrinth	5/62 (8.1%)		2/60 (3.3%)
Endocrine disorders
Endocrine	1/62 (1.6%)		1/60 (1.7%)
Eye disorders
Eye	8/62 (12.9%)		4/60 (6.7%)
Gastrointestinal disorders
Gastrointestinal	50/62 (80.6%)		36/60 (60%)
General disorders
General	37/62 (59.7%)		28/60 (46.7%)
Hepatobiliary disorders
Hepatobiliary	5/62 (8.1%)		2/60 (3.3%)
Immune system disorders
Immune System	4/62 (6.5%)		3/60 (5%)
Infections and infestations
Infections and Infestations	23/62 (37.1%)		22/60 (36.7%)
Injury, poisoning and procedural complications
Injury, Poisoning and Procedural	1/62 (1.6%)		4/60 (6.7%)
Investigations
Investigations	0/62 (0%)		1/60 (1.7%)
Metabolism and nutrition disorders
Metabolism and Nutrition	6/62 (9.7%)		4/60 (6.7%)
Musculoskeletal and connective tissue disorders
Musculoskeletal and Connective Tissue	30/62 (48.4%)		23/60 (38.3%)
Nervous system disorders
Nervous System	6/62 (9.7%)		7/60 (11.7%)
Psychiatric disorders
Psychiatric	5/62 (8.1%)		2/60 (3.3%)
Renal and urinary disorders
Renal and Urinary	2/62 (3.2%)		5/60 (8.3%)
Reproductive system and breast disorders
Reproductive System and Breast	1/62 (1.6%)		1/60 (1.7%)
Respiratory, thoracic and mediastinal disorders
Respiratory, Thoracic and Mediastinal	34/62 (54.8%)		32/60 (53.3%)
Skin and subcutaneous tissue disorders
Skin and Subcutaneous Tissue	20/62 (32.3%)		15/60 (25%)
Surgical and medical procedures
Surgical and Medical Procedures	3/62 (4.8%)		1/60 (1.7%)

Limitations/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.