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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02808871




Registration number
NCT02808871
Ethics application status
Date submitted
20/03/2016
Date registered
22/06/2016
Date last updated
23/09/2019

Titles & IDs
Public title
Phase ll Study of Pirfenidone in Patients With RAILD (TRAIL1)
Scientific title
Phase 2 Study of Safety, Tolerability and Efficacy of Pirfenidone in Patients With Rheumatoid Arthritis Interstitial Lung Disease (TRAIL1)
Secondary ID [1] 0 0
TRAIL1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis Interstitial Lung Disease 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pirfenidone
Treatment: Drugs - Placebo

Experimental: Pirfenidone - Pirfenidone 2403 mg/d for 52 weeks

Placebo Comparator: Placebo - Placebo for 52 weeks


Treatment: Drugs: Pirfenidone
Pirfenidone three times daily (2403 mg) for 52 weeks

Treatment: Drugs: Placebo
Placebo three times daily for 52 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of the composite endpoint - Incidence of the composite endpoint of decline in percent predicted FVC of 10% or greater or death.
Timepoint [1] 0 0
52 weeks
Secondary outcome [1] 0 0
Incidence of the composite endpoint - Incidence of the composite endpoint of decline in percent predicted forced vital capacity (FVC) of 10% or greater
Timepoint [1] 0 0
52 weeks
Secondary outcome [2] 0 0
Frequency of progressive disease - Frequency of progressive disease as defined by OMERACT: FVC% relative decline of >=10% or FVC% change in >=5< 10% and >=15% diffusing capacity (DLCO)
Timepoint [2] 0 0
52 weeks
Secondary outcome [3] 0 0
% FVC change stratified by background therapy
Timepoint [3] 0 0
52 weeks
Secondary outcome [4] 0 0
% FVC change stratified by Usual Interstitial Pneumonitis (UIP) vs. non-UIP pattern on HRCT
Timepoint [4] 0 0
52 weeks
Secondary outcome [5] 0 0
Change in mean slope of FVC
Timepoint [5] 0 0
52 weeks
Secondary outcome [6] 0 0
Time to decline of 10% or greater in percent predicted FVC or death
Timepoint [6] 0 0
52 weeks
Secondary outcome [7] 0 0
All-cause mortality
Timepoint [7] 0 0
52 weeks
Secondary outcome [8] 0 0
Rate of acute exacerbation of interstitial lung disease (ILD)
Timepoint [8] 0 0
52 weeks
Secondary outcome [9] 0 0
All-cause hospitalization
Timepoint [9] 0 0
52 weeks
Secondary outcome [10] 0 0
Hospitalization for respiratory cause
Timepoint [10] 0 0
52 weeks
Secondary outcome [11] 0 0
Incidence of acute exacerbation of ILD
Timepoint [11] 0 0
52 weeks
Secondary outcome [12] 0 0
Number of respiratory exacerbations requiring hospitalizations
Timepoint [12] 0 0
52 weeks
Secondary outcome [13] 0 0
Treatment-emergent Adverse Events (AEs)
Timepoint [13] 0 0
52 weeks
Secondary outcome [14] 0 0
Treatment-emergent serious adverse events (SAEs)
Timepoint [14] 0 0
52 weeks
Secondary outcome [15] 0 0
Treatment-emergent/treatment-related AEs
Timepoint [15] 0 0
52 weeks
Secondary outcome [16] 0 0
Treatment-emergent/treatment-related SAEs
Timepoint [16] 0 0
52 weeks
Secondary outcome [17] 0 0
AEs leading to early discontinuation of study treatment
Timepoint [17] 0 0
52 weeks
Secondary outcome [18] 0 0
Treatment-emergent death or transplant
Timepoint [18] 0 0
52 weeks
Secondary outcome [19] 0 0
Treatment-emergent RA-ILD-related mortality
Timepoint [19] 0 0
52 weeks
Secondary outcome [20] 0 0
Change from Baseline to Week 52 in dyspnea, as measured by the University of California at San Diego Shortness-of-Breath Questionnaire (UCSD SOBQ) score
Timepoint [20] 0 0
52 weeks
Secondary outcome [21] 0 0
Change from Baseline to Week 52 on St. George's Respiratory Questionnaire
Timepoint [21] 0 0
52 weeks

Eligibility
Key inclusion criteria
Diagnosis of Interstitial Lung Disease:

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

2. Diagnosis of RA according to revised 2010 ACR/EULAR criteria

3. Diagnosis of ILD

1. Supported by clinically indicated HRCT, and when available surgical lung biopsy
(SLB).

2. Presence of reticular abnormality affecting more than 10% of the lung parenchyma,
with or without traction bronchiectasis or honeycombing, on HRCT

4. No features supporting an alternative diagnosis on transbronchial biopsy,
bronchoalveolar lavage (BAL), or SLB, if performed

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

1. % predicted FVC = 40% at Screening

2. Change in pre- and post-bronchodilator FVC (measured in liters) between Screening
(Visit 1) and Visit 2 must be a <10% relative difference, calculated as shown
below:

Screen FVC (L) - Day 1 FVC (L) × 100% Screen FVC (L)

3. %predicted DLCO = 30% at Screening

Informed Consent and Protocol Adherence:

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

7. Pregnancy or lactation. 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.

8. 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.
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Disease-Related Exclusions:

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 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:

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

2. Medical history including Human Immunodeficiency Virus (HIV),

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

5. 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

6. Post-bronchodilator FEV1/FVC < 0.7

7. Presence of pleural effusion occupying more than 20% of the hemithorax

8. 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)

9. Coexistent clinically significant COPD/emphysema or asthma in the opinion of the site
principle investigator

Medical Exclusions:

10. 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 4 2weeks prior to the screening visit. Note that prophylactic antibiotics
are not contraindicated or exclusionary.

11. 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 in situ.

12. 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.

13. History of end-stage renal disease requiring dialysis

14. 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.

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

16. History of alcohol or substance abuse in the past 2 years, at the time of screening

17. Family or personal history of long QT syndrome.

Laboratory Exclusions:

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

1. Estimated glomerular filtration rate < 57

2. Electrocardiogram (ECG) with a QTc interval >500 msec at Screening

Medication Exclusions:

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

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

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

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

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

21. 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.

22. Any use of an approved anti-fibrotic medication.

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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
BrisbaneSydneyVIC
Recruitment hospital [1] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
Melbourne Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
QLD 4032 - Chermside
Recruitment postcode(s) [2] 0 0
NSW 2050 - Camperdown
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Utah
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Bristol
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Cambridge
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Exeter
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Leeds
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Leicester
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Liverpool
Country [23] 0 0
United Kingdom
State/province [23] 0 0
London
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Manchester
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Newcastle Upon Tyne
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Norwich
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Oxford
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Southhampton

Funding & Sponsors
Primary sponsor type
Other
Name
Ivan O. Rosas
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02808871
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ivan O. Rosas, M.D.
Address 0 0
Brigham and Women's Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ivan Rosas, M.D.
Address 0 0
Country 0 0
Phone 0 0
617-510-9910
Fax 0 0
Email 0 0
ivan.rosas@bcm.edu
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02808871