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

• Register: ClinicalTrials.gov
• Last refreshed on: 24 August 2021
• Main ID: NCT02808871
• Date of registration: 20/03/2016
• Prospective Registration: Yes
• Primary sponsor: Brigham and Women's Hospital
• 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)
• Date of first enrolment: April 7, 2017
• Target sample size: 123
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02808871
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

Australia, Canada, United Kingdom, United States

Contacts

• Name: Ivan O. Rosas, M.D.
• Affiliation: Brigham and Women's Hospital

Key inclusion & exclusion 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 Grad


Age minimum: 18 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis Interstitial Lung Disease

Intervention(s)

Drug: Placebo

Drug: Pirfenidone

Primary Outcome(s)

Incidence of the composite endpoint [Time Frame: 52 weeks]

Secondary Outcome(s)

AEs leading to early discontinuation of study treatment [Time Frame: 52 weeks]

Change in % predicted FVC [Time Frame: 52 weeks]

Change in absolute value FVC [Time Frame: 52 weeks]

Change in PRO of dyspnea [Time Frame: 52 weeks]

Treatment-emergent RA-ILD-related mortality [Time Frame: 52 weeks]

Acute exacerbation requiring hospitalizations [Time Frame: 52 weeks]

All cause hospitalization [Time Frame: 52 weeks]

Treatment-emergent death or transplant [Time Frame: 52 weeks]

Treatment-emergent serious adverse events (SAEs) [Time Frame: 52 weeks]

Hospitalization for respiratory cause [Time Frame: 52 weeks]

Treatment-emergent/treatment-related AEs [Time Frame: 52 weeks]

All-cause mortality [Time Frame: 52 weeks]

Time to composite of decline in FVC or death [Time Frame: 52 weeks]

Change in slope of absolute FVC [Time Frame: 52 weeks]

Frequency of progressive disease [Time Frame: 52 weeks]

Treatment-emergent Adverse Events (AEs) [Time Frame: 52 weeks]

Treatment-emergent/treatment-related SAEs [Time Frame: 52 weeks]

Change in slope of % predicted FVC [Time Frame: 52 weeks]

Incidence of FVC decline from baseline [Time Frame: 52 weeks]

Secondary ID(s)

2017p000062

Source(s) of Monetary Support

Please refer to primary and secondary sponsors