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

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

• Age 18 through 85 years, inclusive, at Screening
• 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.
• Diagnosis of ILD
• supported by clinically indicated HRCT, and when available, surgical lung biopsy (SLB), prior to Screening, and
• 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
• No features supporting an alternative diagnosis on transbronchial biopsy, or SLB, if performed prior to Screening
• Attainment of the following centralized spirometry criteria (based on local spirometry on standardized equipment and centralized quality controlled):
• percent predicted FVC ≥ 40% at Screening
• change in pre-bronchodilator FVC (measured in liters) between Visit 1 (Screening) and Visit 2 (Randomization) must be a 3 X ULN;
• Alkaline phosphatase > 2.5 X ULN.
• History of end-stage renal disease requiring dialysis
• 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.
• Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone
• History of alcohol or substance abuse in the past 2 years, at the time of Screening
• Family or personal history of long QT syndrome
• Any of the following test criteria above specified limits:
• Estimated glomerular filtration rate 500 msec at Screening
• Prior use of pirfenidone or known hypersensitivity to any of the components of study treatment
• Use of any of the following therapies within 28 days before Screening and during participation in the study:
• Investigational therapy, defined as any drug that has not been approved for marketing for any indication in the country of the participating site
• Potent inhibitors of CYP1A2(e.g. fluvoxamine, enoxacin)
• Potent inducers of CYP1A2.
• Sildenafil (daily use). Note: intermittent use for erectile dysfunction is allowed
• 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.

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