Study of Efficacy and Safety of Pirfenidone in Patients With Fibrotic Hypersensitivity Pneumonitis

The purpose of this study is to evaluate the potential benefits and the safety of treatment
with pirfenidone compared to placebo in subjects with FHP.

STUDY SUMMARY This study will include about 40 subjects at National Jewish Health. This is a
"double blind study" which means neither the subject nor the study staff will know if the
subject is get pirfenidone or placebo during the study. This is done to be sure that no one
knows who is getting pirfenidone or placebo and the effects of the treatment can be measured
objectively, without bias. Subject's that enroll in this study will have an equal chance of
getting pirfenidone or placebo. The decision about which treatment the subject will receive
(randomization) is made through a central organization.

Subjects in the study will receive either pirfenidone (2403 mg every day) or placebo capsules
(a safe, inactive substance that will look the same as the pirfenidone capsules). Both the
placebo and pirfenidone will be supplied in opaque, hard, white gelatin capsules and will be
taken as 3 capsules by mouth, 3 times a day (a total of 9 capsules per day) and should be
taken with food.

Subjects participate in this study, will be asked to take the capsules as prescribed every
day for 52 weeks (12 months).

Inclusion Criteria:

1. Diagnosis of FHP, defined from the first instance in which a patient was informed of
having FHP for at least 3 to 6 months.

2. Age 18 through 80 years at randomization.

3. Diagnosis of possible or definite FHP by HRCT according to pre-specified criteria
(Note: HRCT scan performed within 6 month of the start of screening may be use if it
meets image acquisition guidelines):

i. Definite FHP: Evidence of lung fibrosis (reticular abnormality and/or, traction
bronchiectasis and/or, architectural distortion, and/or honeycombing) and one or more
of the associated finding:

1. Multilobular inspiratory mosaic attenuation

2. Multilobular air trapping on expiratory images

3. Profuse centrilobular ground glass nodular opacities ii. Possible FHP: Evidence
of lung fibrosis (as above) in the absence of any of above associated findings.

a. These patients are required to have a known exposure or BAL lymphocytosis or
transbronchial biopsies demonstrating non-necrotizing granulomas.

FHP Disease Severity and Progression

4. FVC ≥40%, DLCO ≥30% based either on historical pulmonary function tests obtained in
the 30 days prior screening or on tests obtained during screening

5. In the investigator's opinion, no evidence of improvement in measures of FHP disease
severity over the preceding year.

6. Able to walk ≥100 m during the 6-minute walk test (6MWT) at Screening.

Informed Consent and Protocol Adherence

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

8. Able to understand the importance of adherence to study treatment and the study
protocol and willing to follow all study requirements, including the concomitant
medication restrictions, throughout the study

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 at Screening or unwilling to avoid tobacco products throughout
the study

3. Known explanation for the interstitial lung disease, including but not limited to
radiation, drug toxicity, sarcoidosis, pneumoconiosis.

4. Clinical diagnosis of any connective tissue disease, including but not limited to
scleroderma, polymyositis/dermatomyositis, and rheumatoid arthritis.

5. Expected to receive a lung transplant within 6 to12 months from randomization or
on a lung transplant waiting list at randomization.

Medical Exclusions

6. Any condition other than FHP that, in the opinion of the investigator, is likely
to result in the death of the patient within 6 to12 months.

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

8. Pregnancy or lactation. Women of childbearing capacity are required to have a
negative serum pregnancy test before treatment and must agree to maintain highly
effective contraception by practicing abstinence or by using at least two methods
of birth control from the date of consent through the end of the study. If
abstinence is not practiced, one of the two methods of birth control should be an
oral contraceptive (e.g., oral contraceptive and a spermicide).

9. History of ongoing alcohol or substance abuse.

10. History of severe hepatic impairment or end-stage liver disease.

11. History of end-stage renal disease requiring dialysis.

12. Clinical evidence of active infection including, but not limited to, bronchitis,
pneumonia, sinusitis, or urinary tract infection.

13. Unstable or deteriorating cardiac disease, including but not limited to the
following:

1. Unstable angina pectoris or myocardial infarction.

2. Congestive heart failure requiring hospitalization.

3. Uncontrolled clinically significant arrhythmias.