Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: Ribavirin
* Drug: Tenofovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HBV Hepatitis B surface antigen (HBsAg) positive for a minimum of 24 weeks HBV DNA level >20,000 IU/mL ≥ 18 years of age Exclusion Criteria: Willingness and ability to sign an informed consent HBV nucleos(t)ides and/or interferon exposure within 24 weeks of study medication dosing 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) HCV co-infected Cirrhosis (defined by biopsy criteria or as >18.4 kilopascal (kPa) by transient elastography) Creatinine Clearance <60 ml/min Baseline hemoglobin <130 g/L in males and <120 g/L in females Unwilling or unable to use contraception (unless confirmed surgical sterilization) Pregnancy confirmed by blood test

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Open-label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Tenofovir (TDF) 300 mg po once a day (OD) | Drug: Tenofovir<br>* Tenofovir as per standard of care<br>|
| Active Comparator: Group 2<br>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 | Drug: Ribavirin<br>* Ribavirin will be added to the standard of care treatment (tenofovir) regime for 24 weeks.<br>Drug: Tenofovir<br>* Tenofovir as per standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Decline of Participants Serum HBV DNA values for both study arms at each study. | 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). | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fibroscan score | 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. | 24 weeks | 
| Liver enzyme values | Participants individual reduction in liver enzymes at each visit. | 24 weeks | 
| Number of participants with treatment related adverse events as assessed by CTCAE v4.0. | Safety profile of TDF plus Ribavirin regime | 28 weeks |