A Pilot Trial of Herpesvirus Treatment in Idiopathic Pulmonary Fibrosis (IPF)
Condition: Idiopathic Pulmonary Fibrosis
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
Intervention: Valganciclovir; Placebo
Intervention description: Subjects with IPF currently tolerating pirfenidone treatment who have evidence of prior EBV or CMV infection will be randomized to valganciclovir or placebo for 12 weeks.; Subjects with IPF currently tolerating pirfenidone treatment who have evidence of prior EBV or CMV infection will be randomized to valganciclovir or placebo for 12 weeks.
Intervention MeSH terms: Valganciclovir
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 31.0
Sex: All
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: IPF; Herpesvirus; Valganciclovir

Summary:

      The investigators will conduct a single-center, prospective, randomized, placebo-controlled,
      double-blind pilot study of anti-herpesvirus therapy in patients with idiopathic pulmonary
      fibrosis (IPF). Patients with mild, moderate or severe IPF with serologic evidence of current
      or past Epstein-Barr Virus (EBV) or cytomegalovirus (CMV) infection. Randomization will be to
      pirfenidone plus placebo or pirfenidone plus valganciclovir. Thirty subjects will be enrolled
      and randomized to treatment with pirfenidone plus valganciclovir (20 subjects) or pirfenidone
      plus placebo (10 subjects) for 12 weeks. The primary outcome will be safety and tolerability
      will be determined by type, frequency and duration of adverse events (AEs) and serious
      adverse events (SAEs) after 12 weeks of study drug treatment. All study subjects will be
      offered bronchoscopy with bronchoalveolar lavage (BAL) at study initiation and upon
      completion of treatment (12 weeks). Subjects will then be followed up at routine clinic
      visits at 6, 9 and 12 months for data collection.
    

Eligibility criteria:

        Inclusion Criteria:

          1. age >21 and <80 years

          2. ability to provided informed consent

          3. diagnosis of probable or definite IPF according to American Thoracic Society (ATS)
             criteria

          4. tolerance of full-dose (2403 mg/day) pirfenidone

          5. Positive serology for EBV or CMV

        Exclusion Criteria:

          1. FVC < 40% predicted

          2. Diffusing capacity for carbon monoxide (DLCO) < 35% predicted (Crapo)

          3. Forced expiratory volume (FEV)1/FVC <0.7

          4. Significant centrilobular emphysema (>40% by HRCT)

          5. Active tobacco use (cigarette or cigar smoking)

          6. Resting oxygen saturation (SpO2) on room air <89%

          7. Listed for lung transplantation defined as being assigned a lung allocation score

          8. environmental exposure (occupational, environmental, drug, etc.) felt by the principal
             investigator (PI) to be the etiology of the interstitial disease

          9. diagnosis of collagen-vascular conditions (according to the published American College
             of Rheumatology criteria)

         10. history of unstable or deteriorating cardiac disease

         11. acute coronary syndrome, coronary artery bypass, or angioplasty within 3 months of
             screening

         12. uncontrolled arrhythmia

         13. uncontrolled hypertension

         14. known HIV or hepatitis C

         15. known cirrhosis or chronic active hepatitis

         16. active substance or alcohol abuse

         17. pregnancy or lactation

         18. Women of childbearing potential who are not using a medically approved means of
             contraception. Subjects will be considered of childbearing potential if they are not
             surgically sterile or have not been postmenopausal for at least 2 years [any subject
             who is postmenopausal for < 2 years will be required to have a follicle-stimulating
             hormone (FSH) level to assess her potential to become pregnant

         19. clinically relevant lab abnormalities (obtained within 30 days before enrollment),
             including:

               1. creatinine > 2 x upper limit of normal (ULN)

               2. hematology outside of specified limits: white blood cells (WBCs) < 3,500/mm3;
                  hematocrit < 25% or > 59%; platelets < 100,000/mm3;

               3. total bilirubin > 2 x ULN

               4. Aspartate (AST) or alanine aminotransferases (ALT)/ serum glutamic-oxaloacetic;
                  transaminase (SGOT), or serum glutamic pyruvic transaminase (SGPT) > 2.0 x ULN

               5. alkaline phosphatase > 3 x ULN

               6. albumin < 3.0 mg/dL at screening

         20. known hypersensitivity to study medication

         21. any condition that, in the judgment of the PI, might cause participation in this study
             to be detrimental to the subject or that the PI deems makes the subject a poor
             candidate

         22. any therapy with immunosuppressants such as prednisone, azathioprine, or mycophenolate
             currently or anticipated to be needed during the study period (subjects on these drugs
             prior to the study will require a 30-day washout period before randomization)

         23. participation in another IPF clinical treatment trial during the study period (if
             completing another IPF clinical treatment trial, then a 30-day washout period is
             required before randomization)

         24. requirement for chronic suppressive therapy with valacyclovir for recurrent herpes
             virus infection

         25. History of myelodysplasia, aplastic anemia, refractory anemia, or multiple myeloma.