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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02808871
Ethics application status
Date submitted
20/03/2016
Date registered
22/06/2016

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
2017p000062
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
Number of Participants Who Developed Any Element of the Composite Endpoint
Timepoint [1] 0 0
52 weeks
Secondary outcome [1] 0 0
Number of Participants With FVC Decline From Baseline of 10% or Greater
Timepoint [1] 0 0
52 weeks
Secondary outcome [2] 0 0
Number of Participants With Progressive Disease
Timepoint [2] 0 0
52 weeks
Secondary outcome [3] 0 0
Change in Absolute Value FVC Over the 52 Week Study Period
Timepoint [3] 0 0
52 weeks
Secondary outcome [4] 0 0
Change in % Predicted FVC From Baseline to End of Study Over the 52 Week Study Period
Timepoint [4] 0 0
52 weeks
Secondary outcome [5] 0 0
Time to Composite of Decline in FVC or Death
Timepoint [5] 0 0
52 weeks
Secondary outcome [6] 0 0
Change in PRO of Dyspnea
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
All Cause Hospitalization
Timepoint [8] 0 0
52 weeks
Secondary outcome [9] 0 0
Hospitalization for Respiratory Cause
Timepoint [9] 0 0
52 weeks
Secondary outcome [10] 0 0
Acute Exacerbations Requiring Hospitalization
Timepoint [10] 0 0
52 weeks
Secondary outcome [11] 0 0
Treatment-emergent Adverse Events (AEs)
Timepoint [11] 0 0
52 weeks
Secondary outcome [12] 0 0
Treatment-emergent Serious Adverse Events (SAEs)
Timepoint [12] 0 0
52 weeks
Secondary outcome [13] 0 0
Treatment-emergent/Treatment-related AEs
Timepoint [13] 0 0
52 weeks
Secondary outcome [14] 0 0
Treatment-emergent/Treatment-related SAEs
Timepoint [14] 0 0
52 weeks
Secondary outcome [15] 0 0
AEs Leading to Early Discontinuation of Study Treatment
Timepoint [15] 0 0
52 weeks
Secondary outcome [16] 0 0
Treatment-emergent Death or Transplant
Timepoint [16] 0 0
52 weeks
Secondary outcome [17] 0 0
Treatment-emergent RA-ILD-related Mortality
Timepoint [17] 0 0
52 weeks

Eligibility
Key inclusion criteria
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

1. supported by clinically indicated HRCT, and when available, surgical lung biopsy (SLB), prior to Screening, and
2. 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
4. No features supporting an alternative diagnosis on transbronchial biopsy, or SLB, if performed prior to Screening
5. Attainment of the following centralized spirometry criteria (based on local spirometry on standardized equipment and centralized quality controlled):

1. percent predicted FVC = 40% at Screening
2. 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]
3. percent predicted DLCO or TLCO =25 % at Screening
4. Screening (Visit 1) pre-bronchodilator(BD) and Post-BD spirometry meets ATS quality criteria as determined by a central reviewer
5. Baseline (Visit 2) Pre-BD spirometry meets ATS quality criteria as determined by the site Investigator or the central reviewer
6. Able to understand and sign a written informed consent form.
7. 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.

1. 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).
2. 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.
3. 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.
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, as defined below:

1. 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.
2. 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:

1. Other interstitial lung disease, related to but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, or 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 <0.65 at Screening
7. Presence of pleural effusion occupying more than 20% of the hemithorax on Screening HRCT
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 principal investigator
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 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, 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.
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
18. Any of the following test criteria above specified limits:

1. Estimated glomerular filtration rate <30 mL/min/1.73m2
2. ECG with a QTc interval >500 msec at Screening
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. Potent inducers of CYP1A2.
4. 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.

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.
22. Any use of an approved anti-fibrotic medication within 28 days of screening.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/04/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/04/2021
Sample size
Target
Accrual to date
Final
123
Recruitment in Australia
Recruitment state(s)
QLD,SydneyVIC
Recruitment hospital [1] 0 0
Royal Brompton - Brisbane
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
Melbourne Alfred Hospital - Melbourne
Recruitment hospital [4] 0 0
The Prince Charles Hospital - Camperdown
Recruitment postcode(s) [1] 0 0
4032 - Brisbane
Recruitment postcode(s) [2] 0 0
NSW 2050 - Camperdown
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
2050 - Camperdown
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
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
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
Brigham and Women's Hospital
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02808871