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

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ClinicalTrials.gov Identifier: NCT02871401
Recruitment Status : Recruiting
First Posted : August 18, 2016
Last Update Posted : February 21, 2018
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Jonathan Kropski, Vanderbilt University

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.

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: Valganciclovir Drug: Placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase One-B (1B) Pilot Trial of Herpesvirus Treatment in Idiopathic Pulmonary Fibrosis (IPF)
Actual Study Start Date : January 3, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Valganciclovir
Valganciclovir 450 mg, 2 pills by mouth one time per day x 12 weeks
Drug: Valganciclovir
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.
Other Name: Valcyte

Placebo Comparator: Placebo
Placebo, 2 pills by mouth one time per day x 12 weeks
Drug: Placebo
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.




Primary Outcome Measures :
  1. Tolerability [ Time Frame: 12 weeks ]
    Rate of discontinuation of study drug due to adverse events


Secondary Outcome Measures :
  1. Adverse events - Number [ Time Frame: 12 weeks ]
    Number reported adverse events

  2. Adverse events - Frequency [ Time Frame: 12 weeks ]
    Frequency of reported adverse events

  3. Adverse events - Severity [ Time Frame: 12 weeks ]
    Severity of reported adverse events

  4. Change in EBV viral load [ Time Frame: Baseline vs. 12 weeks ]
    EBV viral load in BAL

  5. Change in CMV viral load [ Time Frame: Baseline vs. 12 weeks ]
    CMV viral load in BAL


Other Outcome Measures:
  1. Change in Programmed Death Receptor 1 (PD1) + T cells in peripheral blood [ Time Frame: Baseline vs. 12 weeks ]
    Proportion of PD1 +, cluster of differentiation 4 positive (CD4+) and cluster of differentiation 8 positive (CD8+) cells in peripheral blood

  2. Change in Programmed Death Receptor 1 (PD1) + T cells in peripheral blood [ Time Frame: Baseline vs. 1 year ]
    Proportion of PD1 +, cluster of differentiation 4 positive (CD4+) and cluster of differentiation 8 positive (CD8+) cells in peripheral blood

  3. Change in PD1+ T cells in BAL [ Time Frame: Baseline vs. 12 weeks ]
    Proportion of PD-1 + CD4+ and CD8+ cells in BAL fluid

  4. Change in PD1+ T cells in BAL [ Time Frame: Baseline vs. 1 year ]
    Proportion of PD-1+ CD4+ and CD8+ cells in BAL fluid

  5. Change in T-cell proliferation in peripheral blood [ Time Frame: Baseline vs. 12 weeks ]
    Proportion of proliferating CD4+, CD8+ cells from peripheral blood

  6. Change in T-cell proliferation in peripheral blood [ Time Frame: Baseline vs. 1 year ]
    Proportion of proliferating CD4+, CD8+ cells from peripheral blood

  7. Change in T-cell proliferation in BAL [ Time Frame: Baseline vs. 12 weeks ]
    Proportion of proliferating CD4+, CD8+ T cells from BAL fluid

  8. Change in T-cell proliferation in BAL [ Time Frame: Baseline vs. 1 year ]
    Proportion of proliferating CD4+, CD8+ T cells from BAL fluid

  9. Change in T-cell cytokine production from peripheral blood [ Time Frame: Baseline vs. 12 weeks ]
    EBV/CMV stimulated cytokine production from CD4+, CD8+ T cells from BAL fluid

  10. Change in T-cell cytokine production from peripheral blood [ Time Frame: Baseline vs. 1 year ]
    EBV/CMV stimulated cytokine production from CD4+, CD8+ T cells from BAL fluid

  11. Change in T-cell cytokine production from BAL [ Time Frame: Baseline vs. 12 weeks ]
    EBV/CMV stimulated cytokine production from CD4+, CD8+ T cells from peripheral blood

  12. Change in T-cell cytokine production from BAL [ Time Frame: Baseline vs. 1 year ]
    EBV/CMV stimulated cytokine production from CD4+, CD8+ T cells from peripheral blood

  13. Change in forced vital capacity (FVC) [ Time Frame: Baseline vs. 12 weeks, 1 year ]
    Percent change in FVC compared to baseline

  14. Change in Oxygen requirement [ Time Frame: Baseline vs. 12 weeks ]
    Resting O2 flow (liters per minute)

  15. Change in 6 Minute Walk Test [ Time Frame: Baseline vs. 12 weeks ]
    Distance walked

  16. Acute exacerbations [ Time Frame: 1 year ]
    Acute exacerbation of IPF

  17. Progression free survival [ Time Frame: 12 weeks ]
    Time to 10% FVC decline, respiratory hospitalization, death or lung transplant

  18. Progression free survival [ Time Frame: 1 year ]
    Time to 10% FVC decline, respiratory hospitalization, death or lung transplant

  19. Survival [ Time Frame: 1 year ]
    Time to death or lung transplant



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Ages Eligible for Study:   21 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02871401


Contacts
Contact: Wendi Mason, NP 615-343-7068 wendi.mason@vanderbilt.edu
Contact: Jonathan kropski, MD 615-875-7935 jon.kropski@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Wendi R Mason, NP    615-343-7068    wendi.mason@vanderbilt.edu   
Sponsors and Collaborators
Vanderbilt University Medical Center
Genentech, Inc.
Investigators
Principal Investigator: Jonathan A Kropski, MD Vanderbilt University Medical Center

Responsible Party: Jonathan Kropski, Assistant Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier: NCT02871401     History of Changes
Other Study ID Numbers: 160693
First Posted: August 18, 2016    Key Record Dates
Last Update Posted: February 21, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jonathan Kropski, Vanderbilt University:
IPF
Herpesvirus
Valganciclovir

Additional relevant MeSH terms:
Lung Diseases, Interstitial
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Valganciclovir
Ganciclovir
Antiviral Agents
Anti-Infective Agents