None listed
Conditions
Brief summary
The study drug AB-161 is being developed as a potential new treatment for chronic hepatitis B (CHB) infection. This is the first clinical study where AB-161 will be given to humans. The main goal is to determine whether AB-161 is safe and well tolerated when given at different doses. The levels of the study drug will also be measured at different times. The study may have up to 9 cohorts with 10 healthy volunteers per cohort. The first cohort will start with a conservative dose and dose escalation for each cohort will only occur after review of safety, tolerability, and pharmacokinetics data. The first two subjects in each cohort (except for the food effect panel) will be dosed in a 1:1 ratio of AB-161 to placebo. If the safety profile of the first two subjects is acceptable, the remainder of the subjects will be dosed in a 7:1 ratio of AB-161 to placebo. A separate dosing panel (food effect panel) will evaluate the effect food has on how AB-161 behaves in the body. Subjects will be dosed in a 8:2 ratio of AB-161 to placebo in the food effect panel. The food effect panel will be conducted after cohort 5 at a dose level considered safe and well tolerated.
Interventions
Investigational Product: AB-161
Dosage Formulation: Tablet
Route of Administration: Oral
Cohort 1: Participants will receive a single dose of 2.5 mg of AB-161 or placebo on Day 1
Cohort 2: Participants will receive a single dose of less than or equal to 7.5 mg of AB-161 or placebo on Day 1
Cohort 3: Participants will receive a single dose of less than or equal to 15 mg of AB-161 or placebo on Day 1
Cohort 4: Participants will receive a single dose of less than or equal to 25 mg of AB-161 or plac
Investigational Product: AB-161 Dosage Formulation: Tablet Route of Administration: Oral Cohort 1: Participants will receive a single dose of 2.5 mg of AB-161 or placebo on Day 1 Cohort 2: Participants will receive a single dose of less than or equal to 7.5 mg of AB-161 or placebo on Day 1 Cohort 3: Participants will receive a single dose of less than or equal to 15 mg of AB-161 or placebo on Day 1 Cohort 4: Participants will receive a single dose of less than or equal to 25 mg of AB-161 or placebo on Day 1 Cohort 5: Participants will receive a single dose of less than or equal to 35 mg of AB-161 or placebo on Day 1 Cohort 6: The dose level will be based on safety and PK assessments of previous cohorts. Cohort 7: The dose level will be based on safety and PK assessments of previous cohorts. Cohort 8: The dose level will be based on safety and PK assessments of previous cohorts. For each dosing cohort, 10 subjects will be randomized with 8 receiving AB-161 and 2 receiving placebo. Subjects will receive a single morning dose of study treatment following an overnight fast of at least 10 hours. Dosing will be supervised in the clinic and compliance will be confirmed via mouth checks. Subjects will continue to fast for at least 4 hours after the dose. Additionally, a single Food Effect assessment is to be conducted at a dose considered safe and well-tolerated. 10 subjects (8 active, 2 placebo) will receive a single dose of study treatment (AB-161 or placebo) on Day 1 following a high fat breakfast (approximately 1000 calories with 50%, 30%, and 20% of the calories derived from fat, carbohydrates, and protein, respectively). Subjects will have 30 minutes to complete the meal and the dose of AB-161 should be administered 30 minutes after the start of the meal. No food will be allowed for at least 4 hours post-dose. Sentinel dosing of 2 subjects (1 active, 1 placebo) will occur at each dose level (except for the Food Effect panel). Dose escalation may occur after all available subjects have completed the treatment period and the Safety Review Committee (SRC) reviews all accumulated blinded safety and available PK data. Each cohort will enrol a distinct group of subjects
Sponsors
Arbutus Biopharma Corporation
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Subject must be 18 (or other appropriate age of consent) to 50 years of age, inclusive, at the time of signing the informed consent. Healthy subjects are defined as individuals free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, and clinical laboratory test results. 2. Body mass index (BMI) more than 18 kg per meter square and less than 35 kg per meter square. 3. A male subject is eligible to participate if he does not have a female partner who is pregnant or who intends to become pregnant during the study. Male subjects must agree to use contraception as outlined in the protocol. 4. A female subject is eligible to participate only if she is a NOT a women of childbearing potential (WOCBP). 5. Ability to review and capable of giving signed informed consent which includes compliance with all protocol-specified visit schedules and requirements
Exclusion criteria
1. A history of clinically significant endocrine, gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, cardiovascular, psychiatric or neurologic disorders. 2. Clinically significant ECG abnormalities, blood pressure or laboratory abnormalities, confirmed by repeat. 3. Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV confirmed by polymerase chain reaction (PCR). Evidence of prior HBV vaccination (positive HbsAb) is not exclusionary, and subjects with documented resolved HBV infection (HBsAg and HBV DNA negative) may participate. 4. Subjects who smoke or meet the protocol criteria for substance abuse. 5. Subjects who are unwilling to comply with protocol contraception requirements, and female subjects who are WOCBP, pregnant or breastfeeding.
Outcome results
None listed