Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity

Ottawa Hospital Research Institute24 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatitis B, Chronic

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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).

Time frame: 24 weeks

Secondary Outcomes

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.

Time frame: 24 weeks

Liver enzyme values

Participants individual reduction in liver enzymes at each visit.

Time frame: 24 weeks

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

Safety profile of TDF plus Ribavirin regime

Time frame: 28 weeks

Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts