A Study to investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AB-452 in Healthy Subjects and Subjects with Chronic HBV Infection

INTERVENTION: 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). CONDITION: Chronic HBV Infection PRIMARY OUTCOME: To evaluate the safety and tolerability of AB‐452 following oral administration of single and multiple doses (up to 28 days) to healthy subjects and subjects with CHB as assessed by the frequency and severity of treatment emergent adverse events (TEAEs), discontinuations due to adverse events (AEs), and laboratory abnormalities, by cohort, after single doses or multiple doses up to 28 days of dosing with AB‐452. SECONDARY OUTCOME: Cohort G only, proportion of subjects with a change in HBV‐DNA meeting response criteria (Greater than or equal to 0.5, 1, 2, or 3 log10 reduction; Less than or equal to LLOQ) Part 2: To evaluate the change in HBsAg in CHB subjects over 28 days of dosing of AB‐452. Serum assay tests will be used. Pharmacokinetics (PK) parameters (Cmax, Tmax, AUC, Ctrough) of AB‐452 following administration of AB‐452. 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‐tr