Studying the Treatment Effect of Pirfenidone in Chronic Lung Allograft Dysfunction (STOP-CLAD)
Condition: Disorder Related to Lung Transplantation; Chronic Lung Allograft Dysfunction
Intervention: Pirfenidone Capsule; Placebo Capsule
Intervention description: Dosing:
Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks; Dosing:
Days 1 through 7, 267 mg three times daily;
Days 8 through 14, 534 mg three times daily;
Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 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: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CLAD; Chronic Rejection; Lung Transplant

Summary:

      Greater than 50% of lung transplant recipients show signs of chronic lung allograft
      dysfunction (CLAD) by 5 years post-transplantation.Therapies to prevent or slow CLAD are
      lacking. Anti-fibrotic therapies may offer an avenue to prevent progression of CLAD and
      prolong allograft survival. This study investigates if Pirfenidone therapy will stabilize
      lung function decline and slow progression of Functional small airways disease (fSAD) in lung
      transplant recipients with CLAD.
    

Eligibility criteria:

        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 <15 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