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

NCT ID: NCT02871401

Last Updated: 2022-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-03
• Study Completion Date: 2020-01-31

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.

Conditions

Idiopathic Pulmonary Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Valganciclovir

Valganciclovir 450 mg, 2 pills by mouth one time per day x 12 weeks

Group Type: EXPERIMENTAL

Valganciclovir

Intervention Type: DRUG

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.

Placebo

Placebo, 2 pills by mouth one time per day x 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Valcyte

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Kropski

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan A Kropski, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33740394 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

160693

Identifier Type: -

Identifier Source: org_study_id