Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity

NCT03759782 — Phase 3, Unknown, 24 participants, Ottawa Hospital Research Institute

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Use of Immune Modulatory Properties of Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity: Proposal for Pilot Clinical Trial

Registry	NCT03759782
Status	Unknown
Phase	Phase 3
Study type	Interventional; randomized, parallel, masking: none, treatment
Enrollment	24 (Estimated)
Sponsor	Ottawa Hospital Research Institute (Other)
Conditions	Hepatitis B, Chronic
Interventions	Ribavirin, Tenofovir (Drug)
Dates	start 2019-01-10, primary completion 2022-01-31 (estimated), completion 2022-09-30 (estimated), first posted 2018-11-30, last updated 2021-09-14
Locations	2 sites in Canada

-Summary

Hepatitis B virus (HBV) leads to life-threatening disease like liver failure and liver cancer. For most, a cure is unattainable as current HBV antiviral therapy (using nucleoside analogues) are not able to clear the virus from their liver. While HBV treatments are typically administered alone (monotherapy), this study will explore the use of Ribavirin in combination with standard therapy to enhance current treatment regimens. Ribavirin is commonly used to treat Hepatitis C Virus (HCV) but there is evidence that Ribavirin also induces immune effects that are beneficial in HBV treatment. The aim of this study is to determine whether combination of Ribavirin and a nucleoside analog is more effective compared to nucleoside analog treatment alone. Enrolled patients will be followed for treatment response according to standard clinical and virological tests, as well as immune response to HBV. Our ultimate goal is to find a more effective treatment and improve health outcomes for persons living with HBV.

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+Arms and interventions

Arm	Type	Interventions	Description
Group 1	Experimental	Drug: Tenofovir	Tenofovir (TDF) 300 mg po once a day (OD)
Group 2	Active comparator	Drug: Ribavirin; Drug: Tenofovir	Tenofovir 300 mg po OD + Ribavirin 400 mg twice a day (BID) if <70kg / 600 mg every (q) in the morning (AM) and 400 mg q in the evening (PM) if ≥70kg

Ribavirin (Drug): Ribavirin will be added to the standard of care treatment (tenofovir) regime for 24 weeks.
Tenofovir (Drug): Tenofovir as per standard of care

+Outcome measures

Primary outcomes

The Decline of Participants Serum HBV DNA values for both study arms at each study. [24 weeks]: The absolute decline in HBV DNA and quantitative HBsAg titre will be compared with baseline level at each study visit overall and between study arms (with or without RBV).

Secondary outcomes

Fibroscan score [24 weeks]: Individual fibroscan scores pre and post treatment for each group, using fibrosis scores calculated in kilopascal F0 representing no fibrosis and F4 value indicating cirrhosis.
Liver enzyme values [24 weeks]: Participants individual reduction in liver enzymes at each visit.
Number of participants with treatment related adverse events as assessed by CTCAE v4.0. [28 weeks]: Safety profile of TDF plus Ribavirin regime

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. HBV Hepatitis B surface antigen (HBsAg) positive for a minimum of 24 weeks
2. HBV DNA level >20,000 IU/mL
3. ≥ 18 years of age

Exclusion Criteria:

1. Willingness and ability to sign an informed consent
2. HBV nucleos(t)ides and/or interferon exposure within 24 weeks of study medication dosing
3. HIV and other immune compromising condition (e.g. cancer with the exception of non-invasive cutaneous malignancy, autoimmune condition) or therapy (i.e. systemic steroids, chemotherapy)
4. HCV co-infected
5. Cirrhosis (defined by biopsy criteria or as >18.4 kilopascal (kPa) by transient elastography)
6. Creatinine Clearance <60 ml/min
7. Baseline hemoglobin <130 g/L in males and <120 g/L in females
8. Unwilling or unable to use contraception (unless confirmed surgical sterilization)
9. Pregnancy confirmed by blood test

+Locations (2)

Facility	City	Country	Status
Cumming School of Medicine, University of Calgary	Calgary, Alberta	Canada	Recruiting
Ottawa Hospital Research Institute	Ottawa, Ontario	Canada	Recruiting

+Publications

Results publication: Keeshan A, Coffin C, Vachon A, Patel N, Fung S, Mortimer L, Crawley A, Ma M, Osiowy C, Cooper C. Ribavirin Does Not Enhance Hepatitis B Virus Nucleotide Antiviral Activity: A Pilot Study. Clin Invest Med. 2022 Dec 31;45(4):E11-15. doi: 10.25011/cim.v45i4.39274. PMID 36586101

+Investigators

Curtis L Cooper, MD, Principal investigator, Ottawa Hospital Research Institute

My Notes

Public

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