Studying the Treatment Effect of Pirfenidone in Chronic Lung Allograft Dysfunction (STOP-CLAD)

Inclusion Criteria:

- Lung transplant recipients 18 years of age or older

- Greater than 6 months after single or bilateral lung transplantation

- Baseline FEV1 and FVC values (mean of two highest value measured 3 weeks apart) > 50%
predicted (to assure viable graft)

- Diagnosis of CLAD (two consecutive spirometric values of FEV1 alone or both FEV1 and
FVC < 80% of baseline)

Exclusion Criteria

- Acute Rejection (AR) diagnosis by biopsy in the 28 days prior to enrollment

- Treatment with pulse steroids, Anti-thymocyte Globulin (ATG), extracorporeal
photopheresis (ECP), plasmapheresis, or Immunoglobulin therapy aimed at CLAD within
the 28 days prior to enrollment

- If the subject is receiving chronic Azithromycin therapy, the dose must be stable for
the 28 days prior to enrollment

- Presence of active pulmonary infection at the time of enrollment as determined by an
investigator in consultation with the treating pulmonologist

- Diagnosis of bronchial stenosis either a) requiring stenting, or b) thought to be
responsible for the spirometric decline by principal investigator

- Abnormal liver function tests (aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) > 2 x upper limit of normal (ULN), Alkaline phosphatase > 2.5 x
ULN, total bilirubin > ULN) or known cirrhosis (>2 times upper limit of normal of
AST/ALT/AP)

- Total white blood cell (WBC) < 3.0 K/uL

- Moderate to Severe Renal insufficiency (CrCl <30 mL/min calculated by the
Cockcroft-Gault equation)

- Use of any medication known to cause significant interactions with pirfenidone (strong
CYP1A2 inhibitors such as Fluvoxamine or Enoxacin or inducers)

- Pregnancy or lactation. Women of child-bearing potential will have a pregnancy test at
enrollment and must agree to maintain highly effective contraception with two methods
of birth control from the date of consent through the end of the study.

- Tobacco use within 6 months

- History of alcohol abuse in the past 1 year as determined by the treating
pulmonologist

- Any condition other than CLAD that will likely result in death in the next 1 year

- Any condition in the judgement of the principal investigator that would preclude
participation in this study

- EKG with QTc interval > 500 msec at screening

- Listed for repeat lung transplantation