A study to investigate the Safety, Tolerability, and Pharmacokinetics of AB-506 in Healthy Subjects and Subjects with Chronic HBV Infection
A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Dose Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AB-506, an HBV Capsid Inhibitor, in Healthy Subjects and HBV-DNA Positive Subjects with Chronic HBV Infection
Arbutus Biopharma Corporation
76 participants
Jul 2, 2018
Interventional
Conditions
Summary
The study drug AB-506 is being developed as a potential new treatment for Chronic Hepatitis B (CHB). The main goal of the study is to determine whether AB-506 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. Part 1: Subjects will receive single ascending doses of AB-506 or placebo administered orally. The starting dose will be 30 mg. Subsequent doses in Part 1 will be confirmed after review of safety and PK data from prior dose levels. Part 2: Subjects will receive daily doses of AB-506 or placebo for up to 10 days, administered orally. The dose tested in Part 2 will not exceed the maximum dose tested in Part 1. Part 3: Subjects will receive daily doses of AB-506 or placebo for 28 days, administered orally. The starting dose in Part 3 will not exceed the dose tested in Part 2, and subsequent doses in Part 3 will be confirmed after review of safety and PK data from prior dose levels. Subjects in one of the dosing cohorts will be administered AB-506 with tenofovir (as tenofovir disoproxil fumarate [TDF]), administered orally, for 28 days. This study will help find new methods of treatment for the patients with CHB.
Eligibility
Inclusion Criteria12
- 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.
- Adult male or female subjects, 18 to 65 years of age,
- 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.
- Subjects must be either treatment-naïve or treatment-experienced (off-treatment)
- HBV-DNA >/= 2,000 IU/mL at screening for HBeAg-negative subjects and HBV-DNA >/= 20,000 IU/mL at screening for HBeAg-positive subjects.
- HBsAg >/= 250 IU/mL at screening.
Exclusion Criteria25
- Medical Status or History:
- A history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular disease, or evidence of active or suspected malignancy, or a history of malignancy.
- Findings/Diagnostic Assessments:
- Clinically significant ECG or vital sign abnormalities at Screening, Day -1, or Day 1 pre-dose.
- Clinically significant abnormalities in laboratory test results at Screening or Day -1 that are confirmed by a repeat reading.
- Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
- 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. 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, and/or hepatic encephalopathy.
- c. Liver ultrasound or other imaging with findings suggestive of hepatocellular carcinoma (HCC) at any time.
- 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 within 2 weeks prior to the first dose of study treatment.
- Findings/Diagnostic Assessments at Screening, confirmed by repeat testing:
- ALT or aspartate aminotransferase (AST) >5 × upper limit of normal (ULN).
- Total bilirubin >1.5 × ULN.
- Alpha fetoprotein (AFP) >100 ng/mL. For subjects with AFP results of 50 to 100 ng/mL, historical documentation of a liver ultrasound, computed tomography scan, or magnetic resonance imaging scan performed within 3 months prior to the first dose of study treatment to rule out HCC or other malignancy or liver abnormality must be provided.
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Interventions
The study will be conducted in 3 parts. The first two parts will be conducted in approximately 28 healthy subjects. The third part will be conducted in approximately 48 CHB subjects. Part 1: Subjects will receive single ascending doses of AB-506 or placebo administered orally. The starting dose will be 30 mg. Subsequent doses in Part 1 will be confirmed after review of safety and PK data from prior dose levels. The maximum dose of AB-506 for Part 1 will be no more than 1000 mg. Part 2: Subjects will receive daily doses of AB-506 or placebo for up to 10 days, administered orally. The dose tested in Part 2 will not exceed the maximum dose tested in Part 1. There is no minimum dosing period planned, subjects will continue treatment for up to 10 days unless subject experiences any AE or meets study discontinuation criteria. Part 3: Subjects will receive daily doses of AB-506 or placebo for 28 days, administered orally. The starting dose in Part 3 will not exceed the dose tested in Part 2, and subsequent doses in Part 3 will be confirmed after review of safety and PK data from prior dose levels. Subjects in one of the dosing cohorts will be administered AB-506 with tenofovir (as tenofovir disoproxil fumarate [TDF]), administered orally, as a 300 mg tablet once daily, for 28 days. Parts 1 and 2: Subjects will take their study medication in the presence of study staff. Compliance will be confirmed by a mouth check after dosing. Part 3: 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.
Locations(5)
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ACTRN12618000987268