Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity

Sponsor

Ottawa Hospital Research Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT03759782

Collaborator

(none)

Enrollment

Locations

Arms

44.6

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: Ribavirin Drug: Tenofovir	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Open-labelOpen-label

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 10, 2019

Anticipated Primary Completion Date :

Jan 31, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Group 1

Tenofovir (TDF) 300 mg po once a day (OD)

Drug: Tenofovir

Tenofovir as per standard of care

Active Comparator: Group 2

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

Ribavirin will be added to the standard of care treatment (tenofovir) regime for 24 weeks.

Drug: Tenofovir

Tenofovir as per standard of care

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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