Clinical trial NCT02871401: A Pilot Trial of Herpesvirus Treatment in Idiopathic Pulmonary Fibrosis (IPF)
Official title: A Phase One-B (1B) Pilot Trial of Herpesvirus Treatment in Idiopathic Pulmonary Fibrosis (IPF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: IPF
Herpesvirus
Valganciclovir
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2016-08-18
Enrollment: 31
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Proportion of Subjects Who Discontinue Study Drug Due to Adverse Events
timeFrame: 12 weeks
Secondary outcomes:
measure: Adverse Events - Number
timeFrame: 12 weeks
measure: Serious Adverse Events
timeFrame: 12 weeks
measure: Total # Adverse Events
timeFrame: Randomization to 16 weeks
Other outcomes:
measure: Change in Forced Vital Capacity (FVC)
timeFrame: Baseline vs. 12 weeks, 1 year
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Jonathan A Kropski, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Blackwell TS, Hewlett JC, Mason WR, Martin S, Del Greco J, Ding G, Wu P, Lancaster LH, Loyd JE, Dudenhofer RB, Salisbury ML, Kropski JA. A Phase I Randomized, Controlled, Clinical Trial of Valganciclovir in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2021 Aug;18(8):1291-1297. doi: 10.1513/AnnalsATS.202102-108OC.