Chronic Hepatitis
Conditions
Brief summary
This three-part, Phase 1 protocol will be the first clinical study of AB-836. Parts 1 and 2a/b will be a Phase 1a SAD/MAD of AB-836 in healthy adult subjects. Part 3 will be a Phase 1b dose-ranging assessment of AB-836 in non-cirrhotic Chronic Hepatitis B (CHB) subjects.
Interventions
Sponsors
Arbutus Biopharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Single blind only (Participant) in Part 2b
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Subjects 1. Male and Female (not of childbearing potential in Part 1 and 2a) subjects between 18 and 45 years old 2. Free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, and clinical laboratory test results. 3. BMI of 18-32 kg/m2. * CHB Subjects: 1. Male or female between 18 and 65 years old. 2. Chronic HBV infection documented as a positive HBsAg, HBV DNA, or HBeAg test at least 6 months prior to the Screening Visit, or a historical liver biopsy consistent with chronic HBV infection 3. For cohort F, G, H: 1. HBV DNA ≥2,000 IU/mL at Screening (subjects may be either treatment-naïve or treatment-experienced but currently off-treatment). 2. ALT ≤ 5x ULN 4. For Cohort I: 1. HBV DNA \<LLOQ at Screening 2. Subjects must have been receiving either TAF, TDF, or ETV consistently for ≥6 months prior to Day 1 and are willing to continue with the same NA treatment through the final study visit. 3. ALT ≤ 2.5 x ULN 5. HbsAg ≥250 IU/mL at screening
Exclusion criteria
* CHB Subjects 1. Advanced fibrosis, cirrhosis or other signs of advanced liver disease as assessed by clinical history, ultrasound or FibroScan, or history of cirrhosis or any clinically significant medical condition associated with chronic liver disease. 2. Co-infection with HIV or other non-B hepatitis viruses. 3. Any clinically significant or unstable medical condition or illness that could confound study findings. 4. Subjects who are unwilling to comply with protocol contraception requirements, and female subjects who are pregnant or breastfeeding. 5. Previous treatment with a capsid inhibitor, core inhibitor, or core protein assembly modifier \[CpAM or CAM\]) within 6 months of the Day 1 visit, or prior treatment with an HBV-targeted siRNA or antisense oligonucleotide compound at any time.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of TEAEs | Up to 35 days after last dose of AB-836/placebo |
| Incidence of discontinuations due to AEs | Up to 35 days after last dose of AB-836/placebo |
| Incidence of lab abnormalities | Up to 35 days after last dose of AB-836/placebo |
Countries
Australia, Canada, Hong Kong, Moldova, New Zealand, South Korea, Thailand, Ukraine
Outcome results
None listed