A Pilot Trial of Herpesvirus Treatment in Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase One-B (1B) Pilot Trial of Herpesvirus Treatment in Idiopathic Pulmonary Fibrosis (IPF)

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Valganciclovir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >21 and <80 years ability to provided informed consent diagnosis of probable or definite IPF according to American Thoracic Society (ATS) criteria tolerance of full-dose (2403 mg/day) pirfenidone Positive serology for EBV or CMV Exclusion Criteria: FVC < 40% predicted Diffusing capacity for carbon monoxide (DLCO) < 35% predicted (Crapo) Forced expiratory volume (FEV)1/FVC <0.7 Significant centrilobular emphysema (>40% by HRCT) Active tobacco use (cigarette or cigar smoking) Resting oxygen saturation (SpO2) on room air <89% Listed for lung transplantation defined as being assigned a lung allocation score environmental exposure (occupational, environmental, drug, etc.) felt by the principal investigator (PI) to be the etiology of the interstitial disease diagnosis of collagen-vascular conditions (according to the published American College of Rheumatology criteria) history of unstable or deteriorating cardiac disease acute coronary syndrome, coronary artery bypass, or angioplasty within 3 months of screening uncontrolled arrhythmia uncontrolled hypertension known HIV or hepatitis C known cirrhosis or chronic active hepatitis active substance or alcohol abuse pregnancy or lactation 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 clinically relevant lab abnormalities (obtained within 30 days before enrollment), including: creatinine > 2 x upper limit of normal (ULN) hematology outside of specified limits: white blood cells (WBCs) < 3,500/mm3; hematocrit < 25% or > 59%; platelets < 100,000/mm3; total bilirubin > 2 x ULN Aspartate (AST) or alanine aminotransferases (ALT)/ serum glutamic-oxaloacetic; transaminase (SGOT), or serum glutamic pyruvic transaminase (SGPT) > 2.0 x ULN alkaline phosphatase > 3 x ULN albumin < 3.0 mg/dL at screening known hypersensitivity to study medication 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 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) 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) requirement for chronic suppressive therapy with valacyclovir for recurrent herpes virus infection History of myelodysplasia, aplastic anemia, refractory anemia, or multiple myeloma.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valganciclovir<br>Valganciclovir 450 mg, 2 pills by mouth one time per day x 12 weeks | Drug: Valganciclovir<br>* 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.<br>* Other names: Valcyte;|
| Placebo Comparator: Placebo<br>Placebo, 2 pills by mouth one time per day x 12 weeks | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Who Discontinue Study Drug Due to Adverse Events | Proportion of study subjects who discontinue study drug due to adverse events | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events - Number | Number of subjects with each reported adverse event | 12 weeks | 
| Serious Adverse Events | Number of subjects with each serious adverse event | 12 weeks | 
| Total # Adverse Events | Total number of adverse events | Randomization to 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Herpesvirus, Valganciclovir, IPF