Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity

NCT03759782 | Unknown Phase 3 DMC

• 1 other identifier: 20180733
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Fibroscan score

  24 weeks

• Liver enzyme values

  24 weeks

• Number of participants with treatment related adverse events as assessed by CTCAE v4.0.

  28 weeks

Study Arms (2)

Group 1

EXPERIMENTAL

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

Drug: Tenofovir

Group 2

ACTIVE COMPARATOR

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; Drug: Tenofovir

Interventions

Ribavirin DRUG

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

Group 2

Tenofovir DRUG

Tenofovir as per standard of care

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (2)

Cumming School of Medicine, University of Calgary

Calgary, Alberta, T2N4Z6, Canada

RECRUITING

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H8L6, Canada

RECRUITING

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Ribavirin; Tenofovir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Curtis L Cooper, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Curtis L Cooper, MD

CONTACT

613.737.8924; ccooper@toh.ca

Miriam I Muir, RN BA

CONTACT

613737.8899; mimmuir@toh.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label

Study Record Dates

• First Submitted: October 2, 2018
• First Posted: November 30, 2018
• Study Start: January 10, 2019
• Primary Completion: January 31, 2022
• Study Completion: September 30, 2022
• Last Updated: September 14, 2021

Record last verified: 2021-09

Locations

CA (2)