Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity

Phase 3

• Conditions: Hepatitis B, Chronic
• Interventions: Drug: Tenofovir; Drug: Ribavirin

• Registration Number: NCT03759782
• Lead Sponsor: Ottawa Hospital Research Institute

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-10-02
• Study First Submitted QC: 2018-11-28
• Study First Posted: 2018-11-30
• Study Start: 2019-01-10
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-10
• Last Update Posted: 2021-09-14
• Primary Completion: 2022-01-31
• Study Completion: 2022-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	Tenofovir	Tenofovir (TDF) 300 mg po once a day (OD)
Group 2	Ribavirin	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
Group 2	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
Number of participants with treatment related adverse events as assessed by CTCAE v4.0.	28 weeks	Safety profile of TDF plus Ribavirin regime
Liver enzyme values	24 weeks	Participants individual reduction in liver enzymes at each visit.

Trial Locations

Locations (2)

Cumming School of Medicine, University of Calgary; 🇨🇦 Calgary, Alberta, Canada

Ottawa Hospital Research Institute; 🇨🇦 Ottawa, Ontario, Canada