None listed
Conditions
Brief summary
The study drug AB-452 is being developed as a potential new treatment for Chronic Hepatitis B (CHB). The main goal of the study is to determine whether AB-452 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 and look at whether this is affected by food. The study drug AB-452 is being developed as a potential new treatment for Chronic Hepatitis B (CHB). The main goal of the study is to determine whether AB-452 is safe and well tolerated. The study consists of two parts. In Part 1, healthy subjects will receive single or multiple increasing doses of AB-452. In Part 2, CHB subjects will receive multiple increasing doses of AB-452. Part 1 SAD(Cohorts A and B): Subjects will receive single ascending doses of AB-452 or placebo administered orally. The starting dose will be 30 mg. Subsequent doses in Part 1, will be confirmed after review of safety, tolerability and PK data from prior dose levels. The maximum dose of AB-452 for Part 1 will be no more than 800 mg. Subjects in one of the dosing cohorts (in Cohort A) will be administered single oral dose of AB-452, 2 hours after single oral dose of ranitidine 150mg under fasted conditions. Part 1 MD (Multiple Dose) (Cohort C): Subjects will receive AB-452 or placebo once or twice daily for up to 7 days, administered orally. The dose of AB-452 will be based upon Part 1, SAD. Part 2: CHB Subjects will receive AB-452 or placebo once or twice daily for 28 days, administered orally. The starting dose in Part 2 will not exceed the dose tested in Part 1, MD panel, and subsequent doses in Part 2 will be confirmed after review of safety, virologic and PK data from prior dose levels. This study will help find new methods of treatment for the patients with CHB.
Interventions
The study will be conducted in 2 parts. The first part will be conducted in approximately 28 healthy subjects. The second part will be conducted in approximately 48 CHB subjects.
Part 1 SAD(Cohorts A and B): Subjects will receive single ascending doses of AB-452 or placebo administered orally. The starting dose will be 30 mg. Subsequent doses in Part 1, will be confirmed after review of safety, tolerability and PK data from prior dose levels. The maximum dose of AB-452 for Part 1 will be no more
The study will be conducted in 2 parts. The first part will be conducted in approximately 28 healthy subjects. The second part will be conducted in approximately 48 CHB subjects. Part 1 SAD(Cohorts A and B): Subjects will receive single ascending doses of AB-452 or placebo administered orally. The starting dose will be 30 mg. Subsequent doses in Part 1, will be confirmed after review of safety, tolerability and PK data from prior dose levels. The maximum dose of AB-452 for Part 1 will be no more than 800 mg. Subjects in one of the dosing cohorts (in Cohort A) will be administered single oral dose of AB-452, 2 hours after single oral dose of ranitidine 150mg under fasted conditions. Part 1 MD (Multiple Dose) (Cohort C): Subjects will receive AB-452 or placebo once or twice daily for up to 7 days, administered orally. The dose of AB-452 will be based upon Part 1, SAD. Part 2: CHB Subjects will receive AB-452 or placebo once or twice daily for 28 days, administered orally. The starting dose in Part 2 will not exceed the dose tested in Part 1, MD panel, and subsequent doses in Part 2 will be confirmed after review of safety, virologic and PK data from prior dose levels. Part 1: Subjects will take their study medication in the presence of study staff. Compliance will be confirmed by a mouth check after dosing. Part 2: On days that study drug is taken in the clinic, compliance will be confirmed by a mouth check after dosing. The subject will be instructed to bring all unused study medication in the original containers to each treatment period visit, as well as any empty bottles. The dates and number of tablets dispensed and returned must be recorded on the drug accountability form maintained on-site. In the Part 1 MD panel, all subjects will receive AB-452 once daily or all subjects will receive twice daily dosing. Dosing frequency will be based on Part 1 SAD. The initial dosing frequency in Part 2 (Cohort D) will be based on Part 1 (SAD and MD panels), while the dosing frequency in Cohorts E and F will be based on the totality of data available at that point (SAD, MD, and Cohort D).
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 65 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion Criteria for Study Part 1 (SAD and MD- Healthy Subjects) - Healthy males or females not of childbearing potential aged 18–45, inclusive. - Male subjects must agree to use contraception as detailed in the protocol. - Body mass index (BMI) >/=18 kg/m2 and < /=32 kg/m2. Inclusion Criteria for Study Part 2 (CHB Subjects) - Adult male or female subjects, 18 to 65 years of age, inclusive. - 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. - Body mass index (BMI) >/=18 kg/m2 and < /=38 kg/m2. - Documented chronic HBV infection. - HBV genotype A, B, C or D at Screening. - Quantitative HBsAg >/=1000 IU/mL at the Screening Visit. - Subjects must be HBeAg-negative or HBeAg-positive at least 3 months prior to the Screening Visit. - Subjects must be either treatment naive or on-treatment - Liver ultrasound with absence of clinically significant abnormalities is required < /=6 months prior to Day 1.
Exclusion criteria
Exclusion Criteria for Study Part 1 (SAD and MD- Healthy Subjects) Medical Status or History - A history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, psychiatric, or cardiovascular disease, Gilbert’s Syndrome. - Positive pregnancy test at Screening or Day -1. Findings/Diagnostic Assessments - Clinically significant ECG or vital sign abnormalities at Screening, Day -1, and Day 1 pre-dose. - Clinically significant abnormalities in laboratory test results at Screening or Day -1 that are confirmed by a repeat reading. Exclusion Criteria for Study Part 2 (CHB Subjects) Medical Status or History - Known co-infection with any of the following: a. Human Immunodeficiency Virus (HIV), b. Hepatitis C virus (HCV), c. Hepatitis D virus (HDV), OR d. Active/acute hepatitis E virus (HEV). - Any known pre-existing 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. Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding esophageal varices, hepatorenal syndrome, or hepatic encephalopathy. c. Liver ultrasound or other imaging with findings suggestive of HCC. d. Current or history of any clinically significant cardiac abnormalities/dysfunction. e. Immune-mediated disease or immunosuppression. f. Psychiatric disease. g. Malignancy. h. Clinically unstable medical condition < /=1 week prior to the first dose of study treatment. Findings/Diagnostic Assessments at Screening, Confirmed by Repeat Testing - QTc interval >450 msec for males or >470 msec for females at Screening or baseline (Day 1) visit. - Total bilirubin >1.5 × upper limit of normal.
Outcome results
None listed