The purpose of this study is to determine if vebicorvir (VBR, ABI-H0731) in combination with AB-729 is safe and effective in participants with chronic hepatitis B infection (cHBV) receiving a standard of care nucleos(t)ide/reverse transcriptase inhibitor (SOC NrtI).
The initial cohort of participants will be enrolled in 3 treatment groups receiving 1) VBR + AB-729 + SOC NrtI, 2) VBR + SOC NrtI, or 3) AB-729 + SOC NrtI for up to 48 weeks. At Week 48, all participants will have an assessment of Treatment Stopping Criteria. Any participant who meets the Treatment Stopping Criteria, will discontinue their assigned treatment including NrtI and will remain in follow-up through Week 96. The participants who do not meet the Treatment Stopping Criteria will continue treatment with NrtI alone and will remain in follow-up through Week 96. Up to an additional 2 cohorts may be added to the study in future protocol amendments.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
65
VBR is an HBV core protein inhibitor. Participants will receive VBR 300 mg tablets orally once daily (QD).
AB-729 is a small interfering ribonucleic acid (siRNA) inhibitor of HBV. Participants will receive a 60-mg subcutaneous injection of AB-729 once every 8 weeks.
Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.
Saint Vincent's Hospital Sydney
Darlinghurst, New South Wales, Australia
Saint George Hospital - Australia
Number of Participants With One or More Adverse Events (AEs)
Time frame: AEs were collected from the time of signing the informed consent until the final follow-up visit, up to 96 weeks.
Number of Participants With Premature Treatment Discontinuation Due to AEs
Time frame: AEs were collected from the time of signing the informed consent until the final follow-up visit, up to 96 weeks.
Number of Participants With One or More Abnormal Laboratory Result
Time frame: Laboratory results were collected from the time of signing the informed consent until the study was early terminated, up to 96 weeks.
Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment
Subjects remained on their assigned oral agents (ie, VBR+NrtI for Groups 1 and 2; NrtI for Group 3) until Week 48 laboratory results required for Treatment Stopping Criteria assessment were available so there are some results past Week 48.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56.
Number of Participants With Serum HBsAg Below the Lower Limit of Quantitation (<LLOQ)
Time frame: Pre-specified time points up to 96 weeks
Number of Participants With HBV Deoxyribonucleic Acid (DNA) Not Detected (<5 IU/mL)
Time frame: Week 48
Number of Participants With HBV Ribonucleic Acid (RNA) <LLOQ
Time frame: Week 48
Change From Baseline in Mean log10 HBV RNA On-Treatment
Subjects remained on their assigned oral agents (ie, VBR+NrtI for Groups 1 and 2; NrtI for Group 3) until Week 48 laboratory results required for Treatment Stopping Criteria assessment were available so there are some results past Week 48.
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Kogarah, New South Wales, Australia
Liverpool Hospital
Liverpool, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Footscray Hospital
Footscray, Victoria, Australia
The Alfred Hospital
Melbourne, Victoria, Australia
Melbourne Health
Parkville, Victoria, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia
Diagnostic Consultative Center Aleksandrovska
Sofia, Sofia-Grad, Bulgaria
Acibadem City Clinic Tokuda Hospital
Sofia, Bulgaria
...and 10 more locations
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 56.
Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) On-Treatment
Time frame: Baseline and Week 48
Number of Participants With HBsAg Seroconversion
Time frame: Week 48
Number of Participants With Normal Alanine Aminotransferase (ALT)
Time frame: Baseline and at pre-specified time points up to 96 weeks
Plasma Levels of VBR
Time frame: Before dosing at Baseline (Day 1) and at pre-specified time points up to 48 weeks, and at Week 52
Plasma Levels of AB-729
Time frame: 2 hours after dosing at pre-specified time points up to 40 weeks
Plasma Levels of SOC NrtI (ETV, TDF, TAF)
Time frame: Before dosing at Baseline (Day 1) and at pre-specified time points up to 48 weeks
Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment
Time frame: Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.
Change From Baseline in Mean log10 HBV RNA Off-Treatment
Time frame: Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.
Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment
Time frame: Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.