Study of Efficacy and Safety of Pirfenidone in Patients With Fibrotic Hypersensitivity Pneumonitis
Condition: Interstitial Lung Disease
MeSH terms: Pneumonia; Lung Diseases; Lung Diseases, Interstitial; Alveolitis, Extrinsic Allergic; Hypersensitivity
Intervention: Pirfenidone; Placebo controlled
Intervention description: This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 42-45 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.; This is a single-center, randomized, double-blind, placebo-controlled, efficacy and safety study of pirfenidone in subjects with FHP. Approximately 42-45 subjects will be randomized in a 2:1 ratio to receive pirfenidone 2403 mg/d or placebo for 52 weeks.
Intervention MeSH terms: Pirfenidone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      Patients are being offered participation in this pirfenidone trial because They have been
      diagnosed with fibrotic hypersensitivity pneumonitis (FHP), a type of interstitial lung
      disease (ILD). This is a disease where scarring of lung tissue occurs as the result of
      inhaling substances called antigens. These antigens can be substances such as molds,
      chemicals or dust. As a result of this scarring the lungs are is not able to move oxygen into
      the bloodstream to reach other organs.

      Currently over 1400 subjects have been treated with pirfenidone in 15 clinical trials. This
      drug has been approved by the Food and Drug Administration (FDA) for use in Idiopathic
      Pulmonary Fibrosis, a different type of ILD, but requires special permission for use in your
      condition. The use of pirfenidone has not been approved for the treatment of FHP. It is
      considered experimental treatment in this study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Multidisciplinary consensus 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 typical or compatible FHP by HRCT according to pre-specified criteria
             (Note: HRCT scan performed within 6 months of the start of screening may be used if it
             meets image acquisition guidelines):

             a. Typical FHP: Evidence of lung fibrosis (reticular abnormality and/or, traction
             bronchiectasis and/or, architectural distortion, and/or honeycombing) with either of
             the following: i. Profuse poorly defined centrilobular nodules of ground-glass opacity
             affecting all lung zones.

             ii. Inspiratory mosaic attenuation with the three-density sign. AND iii. Lack of
             features suggesting an alternative diagnosis.

             b. Compatible FHP: Evidence of lung fibrosis (as above) with any of the following: i.
             Patchy or diffuse ground-glass opacity. ii. Patchy, non-profuse centrilobular nodules
             of ground-glass attenuation iii. Mosaic attenuation and lobular air-trapping that do
             not meet the criteria for typical fibrotic HP.

             AND iv. Lack of features suggesting an alternative diagnosis.

             c. Indeterminate FHP: CT signs of fibrosis without other features suggestive of HP and
             lack of features suggesting an alternative diagnosis. These patients are required to
             have a known antigen exposure and BAL lymphocytosis (≥20%) or transbronchial biopsies
             demonstrating non-necrotizing granuloma(s) or lymphocytosis, or surgical lung
             histology consistent with HP.

             FHP Disease Severity and Progression

          4. FVC ≥40%, DLCO ≥30% based either on historical pulmonary function tests obtained in
             the 30 days prior to screening or on tests obtained during screening

          5. In the investigator's opinion, evidence of disease progression: worsening respiratory
             symptoms and an increased in the extent of fibrosis on HRCT or relative decline in the
             FVC% of at least 5%.

          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.

                  Laboratory Exclusions

              14. Any of the following liver function test criteria above specified limits: total
                  bilirubin > 2.0 mg/dL, excluding patients with Gilbert's syndrome; aspartate or
                  alanine aminotransferase (AST/SGOT or ALT/SGPT) >3 ULN; alkaline phosphatase >2.5
                  ULN within past 30 days.

              15. Creatinine clearance <30 mL/min, calculated using the Cockcroft-Gault formula
                  within the past 30 days.

              16. Electrocardiogram with a QTc interval >500 msec at Screening.

                  Medication Exclusions

              17. Prior use of pirfenidone, nintadinib or known hypersensitivity to any of the
                  components of study treatment.

              18. Introduction, increase or escalation of immunosuppressive pharmacological therapy
                  within 1 month (e.g., prednisone, azathioprine, mycophenolic acid and
                  mycophenolate mofetil).

              19. Use of any of the following therapies within 28 days before Screening:

                    1. Bosentan, ambrisentan, cyclophosphamide, cyclosporine, etanercept, iloprost,
                       infliximab, methotrexate, tacrolimus, tetrathiomolybdate, TNF-α inhibitors,
                       imatinib mesylate, Interferon gamma-1b, and tyrosine kinase inhibitors.

                    2. Fluvoxamine.

                    3. Sildenafil (daily use). Note: intermittent use for erectile dysfunction is
                       allowed.