Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Tenofovir; Drug: Ribavirin

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Curtis L Cooper, MD; Phone Number: 613.737.8924; Email: ccooper@toh.ca
• Study Contact Backup: Name: Miriam I Muir, RN BA; Phone Number: 72723 613737.8899; Email: mimmuir@toh.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4Z6
      • Recruiting
      • Cumming School of Medicine, University of Calgary
      • Contact: Carla Coffin, MD; Phone Number: 403-592-5049; Email: cacoffin@ucalgary.ca
      • Contact: Leah Kilvert, BSCN; Phone Number: 403.220.8966; Email: lvkilver@ucalgary.ca
      • Sub-Investigator: Carla Coffin, MD
  • Ontario
    • Ottawa, Ontario, Canada, K1H8L6
      • Recruiting
      • Ottawa Hospital Research Institute
      • Contact: Curtis Cooper, MD; Phone Number: 6137378924; Email: ccooper@toh.ca
      • Contact: Miriam Muir, RN; Phone Number: 72723 6137378899; Email: mmuir@toh.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Curtis L Cooper, MD, Ottawa Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2019
• Primary Completion (Anticipated): January 31, 2022
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Actual): September 14, 2021
• Last Update Submitted That Met QC Criteria: September 10, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Tenofovir; Ribavirin
• Other Study ID Numbers: 20180733

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No