None listed
Conditions
Brief summary
The study drug AB-729 is being developed as a potential new treatment for Chronic Hepatitis B (CHB). The main goal of the study is to determine whether AB-729 is safe and well tolerated when given at different doses. We will also measure the levels of the drug in the blood at different times. The study will be conducted in 3 parts. Study Part 1 (Healthy Subjects SAD) : Part 1 will enroll 24 healthy subjects using a SAD design consisting of 4 sequential dose groups Study Part 2 (Subjects with CHB Infection SAD): Once the safety and tolerability data from the first 2 doses of the SAD assessment in healthy subjects have been completed and it is considered safe to proceed by the SRC, Part 2 will commence in subjects with CHB infection. Study Part 3 (Subjects with CHB Infection MD): Part 3 will be an open-label, Non-Randomized, MD design and will be conducted in 35 subjects with CHB infection. Discontinuation of all HBV treatment is optional. If subjects stop all therapy, they will enter a more intensive follow-up period for 12 months and then have quarterly visits for up to 2 additional years for a total of up to 3 years of follow-up post-NA discontinuation
Interventions
The study will be conducted in 3 parts. Part 3 will be an open-label, Multiple Dose (MD) design and will be conducted in approximately 35 non-cirrhotic CHB infected subjects in up to 5 cohorts (E, F, I, J and G). Part 3 will range from approximately 35 to 102 weeks including Screening and optional treatment extension. Part 3 will commence after the study Safety Review Committee reviews all accumulated non-clinical and study safety and tolerability data up to and including at least 2 single dose
The study will be conducted in 3 parts. Part 3 will be an open-label, Multiple Dose (MD) design and will be conducted in approximately 35 non-cirrhotic CHB infected subjects in up to 5 cohorts (E, F, I, J and G). Part 3 will range from approximately 35 to 102 weeks including Screening and optional treatment extension. Part 3 will commence after the study Safety Review Committee reviews all accumulated non-clinical and study safety and tolerability data up to and including at least 2 single dose cohorts of Part 2 and agrees to proceed. The doses in Cohorts E, F, I, J and G will not exceed those demonstrated to be safe in healthy subject Part 1. Each participant will receive multiple doses of AB-729 (a total of up to 6 doses); frequency of subcutaneous injection will be guided by single dose safety and viral pharmacodynamics in Part 2 but will not be more frequent than monthly. All doses of AB-729 will be administered at the study site by study staff members.
Sponsors
Arbutus Biopharma Corporation
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria for Study Part 3: - Male subjects must agree to use contraception as detailed in the protocol. - Female subjects must not be pregnant and must agree to use contraception as detailed in the protocol. - BMI greater than or equal to 18 kg/m2 and lesser than or equal to 38 kg/m2. - Documented chronic HBV infection as defined in the protocol - HBV-DNA at screening: For HBV-DNA+ subjects (Cohorts G) only: HBV-DNA greater than or equal to 1,000 IU/mL at Screening. For HBV-DNA- subjects (Cohorts E, F, I and J) only: HBV-DNA must be lower than the limit of quantitation at Screening.
Exclusion criteria
Exclusion Criteria for Study Part 3 Known co-infection with any of the following: a. HIV, b. acute hepatitis A virus (HAV), c. HCV, d. hepatitis D virus (HDV), OR e. hepatitis E virus (HEV) infection. Any known preexisting medical or psychiatric condition that could interfere with the subject’s ability to provide informed consent or participate in study conduct, or that may confound study findings including, but not limited to: a. History of any clinically significant medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, Wilson’s disease, a-1-antitrypsin deficiency, alcoholic liver disease, non-alcoholic steatohepatitis, or toxin exposures) that may affect the ability to respond to HBV therapy. b. Immunologically mediated disease or significant immunosuppresion d. Current or history of any clinically significant cardiac abnormalities/dysfunction or uncontrolled hypertension. e. Evidence of decompensated liver disease or findings suggestive of HCC at any time. Evidence of active or suspected malignancy, or a history of malignancy Findings/Diagnostic Assessments at Screening, confirmed by repeat testing: - ALT or AST greater than 2 × upper limit of normal (ULN). - Total bilirubin greater than 1.5 × ULN. - Alpha fetoprotein (AFP) greater than 100 ng/mL.
Outcome results
None listed