A Study to Evaluate the Safety, Tolerability and Antiviral Activity of GS-9688 in Virally-Suppressed Adult Subjects with Chronic Hepatitis B

INTERVENTION: Within each cohort, approximately 25 subjects will be randomized in a 1:2:2 in ratio to one of the three treatment arms (A: B: C). All subjects will remain on their current commercially available OAV therapy for the duration of the study, 48 weeks, in addition to the following treatments: Treatment Arm A: Approximately 5 subjects will be administered placebo‐to‐match (PTM) orally on the same day once a week (every 7 days) for 24 doses Treatment Arm B: Approximately 10 subjects will be administered GS‐9688 1.5 mg orally on the same day once a week (every 7 days) for 24 doses Treatment Arm C: Approximately 10 subjects will be administered GS‐9688 3 mg orally on the same day once a week (every 7 days) for 24 doses All GS‐9688 study drug doses will be administered in fasted state. Study drug will be administered at approximately the same time each day following an overnight fast (no food or drinks, except water, for at least 8 hours with no food or drinks, including water, for the 1 hour before dosing). After dosing, subjects will continue to fast (no food or drinks, including water) for 2 hours. After 2 hours postdose, water is allowed and after 4 hours postdose,patients are allowed to eat any food or drinks. After the 24th dose (Week 23 visit), GS‐9688/PTM will be discontinued. Subjects will continue being treated with their original approved OAV and will be followed until the end of study (Week 48/ED). The total study duration for each subject will be 48 weeks inclusive of the treatment period. Subjects should take their OAV treatment and other commercially available medications no earlier than 2 hours after GS‐9688/PTM dosing. Drug accountability will be performed at every in‐clinic visit through capsule count. CONDITION: Chronic Hepatitis B PRIMARY OUTCOME: ‐To evaluate the safety and tolerability of multiple oral doses of GS‐9688 at Week 24 in virally suppressed chronic hepatitis B (CHB) adult subjects on oral antivirals (OAV) ; SECONDARY OUTCOME: To evaluate the antiviral activity of GS‐9688 at Weeks 4, 8, 12 and 48 as measured by the proportion of subjects with greater than or equal to 1 log10 IU/mL decline from baseline in serum qHBsAg INCLUSION CRITERIA: Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures 2) Adult male and non‐pregnant, non‐lactating female subjects, 18‐65 years of age inclusive based on the date of the Screening visit 3) Documented evidence of chronic HBV infection (e.g. HBsAg positive for more than 6 months) with detectable HBsAg levels at Screening 4) Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline prior to enrollment. 5) Male and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception 6) Have been on commercially available HBV OAV treatment(s) (tenofovir alafenamide, tenofovir disoproxil fumurate, entecavir, adefovir, lamivudine, telbivudine, either as single agent