Chronic Hepatitis B
Conditions
Keywords
cHBV, HBV, hepatitis B, vebicorvir, VBR, AB-729
Brief summary
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).
Detailed description
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.
Interventions
DRUGVBR
VBR is an HBV core protein inhibitor. Participants will receive VBR 300 mg tablets orally once daily (QD).
DRUGAB-729
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.
DRUGSOC NrtI
Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.
Sponsors
Arbutus Biopharma Corporation
Assembly Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Body mass index (BMI) 18 to 36 kg/m\^2 and a minimum body weight of 45 kg (inclusive) * Female participants must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1 * Chronic Hepatitis B defined as HBV infection documented for ≥6 months prior to Screening * Hepatitis B 'e' antigen (HBeAg) negative at least 3 months prior to Screening Visit (historical documentation) AND at the Screening Visit * Virologically suppressed on SOC NrtI therapy with nonquantifiable HBV DNA for at least 6 months prior to Screening * On a stable SOC NrtI regimen of ETV, TDF, or TAF for \>12 months * HBsAg ≥100 international units/mL at Screening * Lack of bridging fibrosis or cirrhosis * Agreement to comply with protocol-specified contraceptive requirements * In good general health, except for cHBV, in the opinion of the Investigator * Able to take oral medication and willing to receive subcutaneous injections of AB-729.
Exclusion criteria
* Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis D virus (HDV), acute hepatitis A virus (HAV), or acute hepatitis E virus (HEV) * Females who are lactating or wish to become pregnant during the course of the study * History of liver transplant or evidence of advanced liver disease, cirrhosis, or hepatic decompensation at any time prior to, or at the time of Screening * History of persistent alcohol abuse or illicit drug abuse within 3 years prior to Screening * Clinically significant diseases or conditions, such as cardiac disease, including poorly-controlled or unstable hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease; liver disease other than cHBV; endocrine disorder; autoimmune disorder; poorly controlled diabetes mellitus; neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment; ongoing infection or other medical conditions requiring frequent medical management or pharmacologic or surgical treatment that, in the opinion of the Investigator or the Sponsor, makes the subject unsuitable for study participation * History of hepatocellular carcinoma (HCC) * History of malignancy other than HCC unless the subject's malignancy has been in complete remission off chemotherapy and without additional medical or surgical interventions during the 3 years before Screening * History or presence at Screening of electrocardiogram (ECG) abnormalities deemed clinically significant, in the opinion of the Investigator * History of hypersensitivity or idiosyncratic reaction to any components or excipients of the investigational drugs * History of any significant food or drug-related allergic reactions such as anaphylaxis or Stevens-Johnson syndrome * Exclusionary laboratory results at Screening: 1. Platelet count \<100,000/mm\^3 2. Albumin \<3 g/dL 3. Direct bilirubin \>1.2× upper limit of normal (ULN) 4. ALT ≥5× ULN 5. Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is \> ULN but \<100 ng/mL, the subject is eligible if hepatic imaging prior to initiation of study drug reveals no lesions indicative of possible HCC 6. International Normalized Ratio (INR) \>1.5× ULN 7. Estimated creatinine clearance (CrCl) \<50 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight at Screening 8. Any other laboratory abnormality deemed clinically significant by the Investigator * Current or prior use of prohibited (per protocol) concomitant medications from 28 days prior to Day 1. * Current or prior treatment for cHBV with: * Lamivudine, telbivudine or adefovir (any duration) * HBV core inhibitor (any duration) * siRNA or other oligonucleotide therapeutic (any duration) * Interferon in the 6 months prior to Screening * Any investigational agent for cHBV in the 6 months prior to Screening. * Participation in another clinical study of a drug or device whereby the last investigational drug/device administration is within 60 days or 5 half-lives prior to study start.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With One or More Adverse Events (AEs) | 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 | 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 | Laboratory results were collected from the time of signing the informed consent until the study was early terminated, up to 96 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With HBV Ribonucleic Acid (RNA) <LLOQ | Week 48 | — |
| Change From Baseline in Mean log10 HBV RNA On-Treatment | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 56. | 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. |
| Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) On-Treatment | Baseline and Week 48 | — |
| Number of Participants With HBsAg Seroconversion | Week 48 | — |
| Number of Participants With Normal Alanine Aminotransferase (ALT) | Baseline and at pre-specified time points up to 96 weeks | — |
| Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56. | 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. |
| Plasma Levels of AB-729 | 2 hours after dosing at pre-specified time points up to 40 weeks | — |
| Plasma Levels of SOC NrtI (ETV, TDF, TAF) | 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 | Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96. | — |
| Change From Baseline in Mean log10 HBV RNA Off-Treatment | 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 | Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96. | — |
| Plasma Levels of VBR | Before dosing at Baseline (Day 1) and at pre-specified time points up to 48 weeks, and at Week 52 | — |
| Number of Participants With Serum HBsAg Below the Lower Limit of Quantitation (<LLOQ) | Pre-specified time points up to 96 weeks | — |
| Number of Participants With HBV Deoxyribonucleic Acid (DNA) Not Detected (<5 IU/mL) | Week 48 | — |
Countries
Australia, Bulgaria, Canada, New Zealand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VBR + AB-729 + SOC NrtI Participants with cHBV received VBR + AB-729 + SOC NrtI for 48 weeks followed by 48 weeks in follow-up or until the study was early terminated.
VBR: VBR is an HBV core protein inhibitor. Participants received VBR 300 mg tablets orally once daily (QD).
AB-729: AB-729 is a small interfering ribonucleic acid (siRNA) inhibitor of HBV. Participants received a 60-mg subcutaneous injection of AB-729 once every 8 weeks.
SOC NrtI: Participants received their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert. | 32 |
| VBR + SOC NrtI Participants with cHBV received VBR + SOC NrtI for 48 weeks followed by 48 weeks in follow-up or until the study was early terminated. This treatment was used as a reference regimen.
VBR: VBR is an HBV core protein inhibitor. Participants received VBR 300 mg tablets orally once daily (QD).
SOC NrtI: Participants received their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert. | 16 |
| AB-729 + SOC NrtI Participants with cHBV received AB-729 + SOC NrtI for 48 weeks followed by 48 weeks in follow-up or until the study was early terminated. This treatment was used as a reference regimen.
AB-729: AB-729 is a small interfering ribonucleic acid (siRNA) inhibitor of HBV. Participants received a 60-mg subcutaneous injection of AB-729 once every 8 weeks.
SOC NrtI: Participants received their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert. | 17 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Study Termination | 25 | 13 | 14 |
| Overall Study | Withdrawal by Subject | 5 | 2 | 3 |
Baseline characteristics
| Characteristic | VBR + AB-729 + SOC NrtI | VBR + SOC NrtI | AB-729 + SOC NrtI | Total |
|---|---|---|---|---|
| Age, Continuous | 40 years STANDARD_DEVIATION 6.1 | 41 years STANDARD_DEVIATION 6.4 | 42 years STANDARD_DEVIATION 5.9 | 41 years STANDARD_DEVIATION 6.1 |
| ALT (U/L) | 29 U/L STANDARD_DEVIATION 19.8 | 27 U/L STANDARD_DEVIATION 12.8 | 28 U/L STANDARD_DEVIATION 17.3 | 28 U/L STANDARD_DEVIATION 17.4 |
| Baseline HBeAb Negative | 7 Participants | 2 Participants | 0 Participants | 9 Participants |
| Baseline HBeAb Positive | 25 Participants | 14 Participants | 17 Participants | 56 Participants |
| Baseline HBsAb Negative | 32 Participants | 16 Participants | 17 Participants | 65 Participants |
| Baseline HBsAb Positive | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Body Mass Index | 25.6 kg/m^2 STANDARD_DEVIATION 4.21 | 26.1 kg/m^2 STANDARD_DEVIATION 4.67 | 24.1 kg/m^2 STANDARD_DEVIATION 3.26 | 25.3 kg/m^2 STANDARD_DEVIATION 4.12 |
| Body Weight | 73.8 kg STANDARD_DEVIATION 15.77 | 74.2 kg STANDARD_DEVIATION 15.38 | 69.2 kg STANDARD_DEVIATION 12.22 | 72.7 kg STANDARD_DEVIATION 14.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 16 Participants | 17 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fibroscan Result (kPa) | 5.2 kPa STANDARD_DEVIATION 1.22 | 5.6 kPa STANDARD_DEVIATION 1.04 | 5.0 kPa STANDARD_DEVIATION 1.13 | 5.3 kPa STANDARD_DEVIATION 1.16 |
| HBcrAg (Log10 U/mL) | 3.3 Log10 U/mL STANDARD_DEVIATION 1.22 | 3.3 Log10 U/mL STANDARD_DEVIATION 1.43 | 3.2 Log10 U/mL STANDARD_DEVIATION 0.89 | 3.3 Log10 U/mL STANDARD_DEVIATION 1.19 |
| HBsAg (Log10 IU/mL) | 3.4 Log10 IU/mL STANDARD_DEVIATION 0.57 | 3.3 Log10 IU/mL STANDARD_DEVIATION 0.62 | 3.3 Log10 IU/mL STANDARD_DEVIATION 0.56 | 3.3 Log10 IU/mL STANDARD_DEVIATION 0.57 |
| HBV DNA (log10 IU/mL) | 0.7 Log10 IU/mL STANDARD_DEVIATION 0 | 0.7 Log10 IU/mL STANDARD_DEVIATION 0 | 0.7 Log10 IU/mL STANDARD_DEVIATION 0 | 0.7 Log10 IU/mL STANDARD_DEVIATION 0 |
| HBV Genotype A | 4 Participants | 0 Participants | 2 Participants | 6 Participants |
| HBV Genotype B | 6 Participants | 4 Participants | 3 Participants | 13 Participants |
| HBV Genotype B/C | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| HBV Genotype C | 5 Participants | 2 Participants | 4 Participants | 11 Participants |
| HBV Genotype C/B | 4 Participants | 1 Participants | 2 Participants | 7 Participants |
| HBV Genotype C/E | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| HBV Genotype D | 6 Participants | 4 Participants | 4 Participants | 14 Participants |
| HBV Genotype D/B | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| HBV Genotype E | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| HBV Genotype Unable to Genotype | 2 Participants | 5 Participants | 2 Participants | 9 Participants |
| HBV RNA (log10 U/mL) | 1.2 Log10 IU/mL STANDARD_DEVIATION 0.88 | 1.1 Log10 IU/mL STANDARD_DEVIATION 0.69 | 1.4 Log10 IU/mL STANDARD_DEVIATION 0.88 | 1.2 Log10 IU/mL STANDARD_DEVIATION 0.83 |
| HBV TNA Quantitative (Log10 U/mL) | 1.2 Log10 IU/mL STANDARD_DEVIATION 0.41 | 1.1 Log10 IU/mL STANDARD_DEVIATION 0.32 | 1.2 Log10 IU/mL STANDARD_DEVIATION 0.49 | 1.1 Log10 IU/mL STANDARD_DEVIATION 0.41 |
| Metavir Fibrosis Stage F0-F2 | 32 Participants | 16 Participants | 17 Participants | 65 Participants |
| Metavir Fibrosis Stage F3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Metavir Fibrosis Stage F4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| NrtI at Baseline Entecavir (ETV) | 8 Participants | 5 Participants | 2 Participants | 15 Participants |
| NrtI at Baseline Tenofovir Alafenamide (TAF) | 6 Participants | 3 Participants | 2 Participants | 11 Participants |
| NrtI at Baseline Tenofovir disoproxil fumarate (TDF) | 18 Participants | 8 Participants | 13 Participants | 39 Participants |
| Race/Ethnicity, Customized American Indian / Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 17 Participants | 10 Participants | 10 Participants | 37 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 6 Participants | 6 Participants | 22 Participants |
| Sex: Female, Male Female | 20 Participants | 13 Participants | 10 Participants | 43 Participants |
| Sex: Female, Male Male | 12 Participants | 3 Participants | 7 Participants | 22 Participants |
| Years on current HBV treatment | 6.9 years STANDARD_DEVIATION 3.92 | 4.8 years STANDARD_DEVIATION 2.67 | 5.9 years STANDARD_DEVIATION 3.52 | 6.1 years STANDARD_DEVIATION 3.61 |
| Years positive for HBV | 14.5 years STANDARD_DEVIATION 7.75 | 13.1 years STANDARD_DEVIATION 11.01 | 15.4 years STANDARD_DEVIATION 8.78 | 14.4 years STANDARD_DEVIATION 8.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 16 | 0 / 17 |
| other Total, other adverse events | 31 / 32 | 16 / 16 | 17 / 17 |
| serious Total, serious adverse events | 1 / 32 | 0 / 16 | 0 / 17 |
Outcome results
Primary
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VBR + AB-729 + SOC NrtI | Number of Participants With One or More Abnormal Laboratory Result | 30 Participants |
| VBR + SOC NrtI | Number of Participants With One or More Abnormal Laboratory Result | 16 Participants |
| AB-729 + SOC NrtI | Number of Participants With One or More Abnormal Laboratory Result | 16 Participants |
Primary
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VBR + AB-729 + SOC NrtI | Number of Participants With One or More Adverse Events (AEs) | 26 Participants |
| VBR + SOC NrtI | Number of Participants With One or More Adverse Events (AEs) | 12 Participants |
| AB-729 + SOC NrtI | Number of Participants With One or More Adverse Events (AEs) | 12 Participants |
Primary
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.
Population: Subjects in the arm receiving only AB-720 and SOC NrtL were not evaluated for VBR discontinuation. Subjects in the arm reviewing only VBR and SOC NrtI were not evaluated for AB-720 discontinuation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VBR + AB-729 + SOC NrtI | Number of Participants With Premature Treatment Discontinuation Due to AEs | AB-729 discontinuation due to AE | 1 Participants |
| VBR + AB-729 + SOC NrtI | Number of Participants With Premature Treatment Discontinuation Due to AEs | VBR discontinuation due to AE | 3 Participants |
| VBR + SOC NrtI | Number of Participants With Premature Treatment Discontinuation Due to AEs | VBR discontinuation due to AE | 1 Participants |
| AB-729 + SOC NrtI | Number of Participants With Premature Treatment Discontinuation Due to AEs | AB-729 discontinuation due to AE | 0 Participants |
Secondary
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.
Population: Due to study early termination, not all subjects reached week 96.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 16 | 0 log10 U/mL | Standard Deviation 1.25 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 12 | -0.7 log10 U/mL | Standard Deviation 1.11 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 36 | 0 log10 U/mL | Standard Deviation 0 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 32 | .2 log10 U/mL | Standard Deviation 0.3 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 28 | 0 log10 U/mL | Standard Deviation 0 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 8 | -0.5 log10 U/mL | Standard Deviation 0.93 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 4 | -0.6 log10 U/mL | Standard Deviation 0.83 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 24 | .5 log10 U/mL | Standard Deviation 0.41 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 20 | .7 log10 U/mL | Standard Deviation 0.77 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 8 | -0.5 log10 U/mL | Standard Deviation 1.02 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 4 | -0.8 log10 U/mL | Standard Deviation 1.03 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 12 | -0.6 log10 U/mL | Standard Deviation 1.24 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 16 | -0.5 log10 U/mL | Standard Deviation 0.55 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 20 | -0.3 log10 U/mL | Standard Deviation 1.45 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 24 | -0.4 log10 U/mL | Standard Deviation 1.09 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 28 | -0.8 log10 U/mL | Standard Deviation 0.17 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 32 | -1.0 log10 U/mL | Standard Deviation 1.26 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 36 | -1.0 log10 U/mL | Standard Deviation 0.51 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 40 | -0.9 log10 U/mL | Standard Deviation 0.37 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 44 | -1.0 log10 U/mL | Standard Deviation 0.39 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 48 | -1.2 log10 U/mL | — |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 4 | -0.1 log10 U/mL | Standard Deviation 0.57 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 32 | -0.2 log10 U/mL | — |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 28 | -0.7 log10 U/mL | — |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 16 | 0.3 log10 U/mL | Standard Deviation 0.31 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 8 | 0 log10 U/mL | Standard Deviation 0.36 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 36 | 0 log10 U/mL | — |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 24 | -0.4 log10 U/mL | Standard Deviation 0.25 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 20 | -0.2 log10 U/mL | Standard Deviation 0.01 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 12 | -0.2 log10 U/mL | Standard Deviation 0.28 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 8 | -0.8 log10 U/mL | Standard Deviation 0.63 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 20 | -0.6 log10 U/mL | Standard Deviation 0.9 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 24 | -0.5 log10 U/mL | Standard Deviation 0.2 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 28 | -0.6 log10 U/mL | Standard Deviation 0.03 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 4 | -1.1 log10 U/mL | Standard Deviation 0.61 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 40 | -0.4 log10 U/mL | — |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 32 | -0.1 log10 U/mL | — |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 12 | -0.8 log10 U/mL | Standard Deviation 0.66 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 16 | -0.8 log10 U/mL | Standard Deviation 0.66 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 36 | .5 log10 U/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 4 | -0.9 log10 U/mL | Standard Deviation 1.05 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 40 | -0.6 log10 U/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 24 | 0.7 log10 U/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 16 | -0.9 log10 U/mL | Standard Deviation 0.93 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 12 | -1.0 log10 U/mL | Standard Deviation 0.78 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 28 | -0.6 log10 U/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 8 | -0.9 log10 U/mL | Standard Deviation 0.56 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 36 | -0.1 log10 U/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 44 | .1 log10 U/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 20 | -0.7 log10 U/mL | Standard Deviation 0.65 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 HBV RNA Off-Treatment | Off-Treatment Week 32 | -0.3 log10 U/mL | — |
Secondary
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.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 56.
Population: The number analyzed differs from the overall number analyzed due to early terminated and/or withdrawn subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 20 | -0.7 log10 U/mL | Standard Deviation 1.01 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 52 | -0.7 log10 U/mL | Standard Deviation 0.89 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 36 | -0.7 log10 U/mL | Standard Deviation 0.88 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 24 | -0.5 log10 U/mL | Standard Deviation 0.89 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 8 | -.7 log10 U/mL | Standard Deviation 1.01 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 32 | -0.7 log10 U/mL | Standard Deviation 0.89 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 28 | -0.9 log10 U/mL | Standard Deviation 1 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 56 | -1.0 log10 U/mL | Standard Deviation 1.37 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 48 | -0.7 log10 U/mL | Standard Deviation 1.03 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 12 | -.6 log10 U/mL | Standard Deviation 1 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 4 | -.7 log10 U/mL | Standard Deviation 0.76 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 44 | -0.6 log10 U/mL | Standard Deviation 0.87 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 16 | -0.6 log10 U/mL | Standard Deviation 0.94 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 2 | -.6 log10 U/mL | Standard Deviation 0.75 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 40 | -0.6 log10 U/mL | Standard Deviation 0.88 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 56 | .2 log10 U/mL | Standard Deviation 0.62 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 4 | 0.2 log10 U/mL | Standard Deviation 0.77 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 8 | 0 log10 U/mL | Standard Deviation 0.59 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 12 | 0 log10 U/mL | Standard Deviation 0.55 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 16 | 0 log10 U/mL | Standard Deviation 0.58 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 20 | .1 log10 U/mL | Standard Deviation 0.59 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 24 | .2 log10 U/mL | Standard Deviation 0.54 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 28 | .2 log10 U/mL | Standard Deviation 0.65 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 32 | .1 log10 U/mL | Standard Deviation 0.55 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 36 | .1 log10 U/mL | Standard Deviation 0.5 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 40 | .1 log10 U/mL | Standard Deviation 0.68 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 44 | 0 log10 U/mL | Standard Deviation 0.51 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 48 | -0.1 log10 U/mL | Standard Deviation 0.6 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 52 | -0.1 log10 U/mL | Standard Deviation 0.6 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 2 | -.2 log10 U/mL | Standard Deviation 0.7 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 16 | -0.8 log10 U/mL | Standard Deviation 0.6 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 48 | -0.7 log10 U/mL | Standard Deviation 0.46 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 40 | -0.6 log10 U/mL | Standard Deviation 0.57 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 12 | -0.7 log10 U/mL | Standard Deviation 0.78 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 4 | -.6 log10 U/mL | Standard Deviation 0.86 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 44 | -0.8 log10 U/mL | Standard Deviation 0.69 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 28 | -0.8 log10 U/mL | Standard Deviation 0.59 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 24 | -0.7 log10 U/mL | Standard Deviation 0.64 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 8 | -0.5 log10 U/mL | Standard Deviation 0.65 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 32 | -0.7 log10 U/mL | Standard Deviation 0.68 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 20 | -0.8 log10 U/mL | Standard Deviation 0.56 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 2 | -.4 log10 U/mL | Standard Deviation 0.48 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 HBV RNA On-Treatment | Week 36 | -0.7 log10 U/mL | Standard Deviation 0.78 |
Secondary
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.
Population: Due to study early termination, not all subjects reached week 96.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 24 | -0.3 log10 U/mL | Standard Deviation 0.17 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 12 | -0.3 log10 U/mL | Standard Deviation 0.46 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 36 | -0.3 log10 U/mL | Standard Deviation 0.07 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 36 | -0.2 log10 U/mL | Standard Deviation 0.07 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 48 | -0.1 log10 U/mL | Standard Deviation 0.14 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 24 | -0.2 log10 U/mL | Standard Deviation 0.15 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 12 | -0.5 log10 U/mL | Standard Deviation 0.81 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 24 | .8 log10 U/mL | Standard Deviation 1.13 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 36 | 0 log10 U/mL | — |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 12 | .1 log10 U/mL | Standard Deviation 0.48 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 36 | -0.2 log10 U/mL | — |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 24 | -0.2 log10 U/mL | Standard Deviation 0.06 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 12 | -0.1 log10 U/mL | Standard Deviation 0.18 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 48 | 0 log10 U/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 12 | -0.6 log10 U/mL | Standard Deviation 0.7 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 24 | -0.2 log10 U/mL | Standard Deviation 0.07 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment | Off-Treatment Week 36 | 0 log10 U/mL | — |
Secondary
Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) On-Treatment
Time frame: Baseline and Week 48
Population: The number analyzed differs from the overall number analyzed due to early terminated and/or withdrawn subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) On-Treatment | -0.4 log10 U/mL | Standard Deviation 0.7 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) On-Treatment | 0 log10 U/mL | Standard Deviation 0.58 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) On-Treatment | -0.3 log10 U/mL | Standard Deviation 0.53 |
Secondary
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.
Population: Not all subjects reached Week 96 due to study termination.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 16 | -1.7 log10 IU/mL | Standard Deviation 0.24 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 12 | -1.8 log10 IU/mL | Standard Deviation 0.54 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 36 | -1.6 log10 IU/mL | Standard Deviation 0.04 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 32 | -1.7 log10 IU/mL | Standard Deviation 0.2 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 28 | -1.8 log10 IU/mL | Standard Deviation 0.13 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 8 | -1.9 log10 IU/mL | Standard Deviation 0.54 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 4 | -1.9 log10 IU/mL | Standard Deviation 0.51 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 24 | -1.7 log10 IU/mL | Standard Deviation 0.13 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 20 | -1.8 log10 IU/mL | Standard Deviation 0.18 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 8 | -1.4 log10 IU/mL | Standard Deviation 0.32 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 4 | -1.6 log10 IU/mL | Standard Deviation 0.53 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 12 | -1.4 log10 IU/mL | Standard Deviation 0.54 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 16 | -1.5 log10 IU/mL | Standard Deviation 0.64 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 20 | -1.7 log10 IU/mL | Standard Deviation 0.85 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 24 | -2.0 log10 IU/mL | Standard Deviation 0.78 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 28 | -2.0 log10 IU/mL | Standard Deviation 0.73 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 32 | -1.9 log10 IU/mL | Standard Deviation 0.72 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 36 | -1.8 log10 IU/mL | Standard Deviation 0.63 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 40 | -1.7 log10 IU/mL | Standard Deviation 0.68 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 44 | -1.6 log10 IU/mL | Standard Deviation 0.56 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 48 | -2.2 log10 IU/mL | — |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 4 | 0 log10 IU/mL | Standard Deviation 0.09 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 32 | 0.0 log10 IU/mL | — |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 28 | 0 log10 IU/mL | — |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 16 | -0.1 log10 IU/mL | Standard Deviation 0.09 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 8 | 0 log10 IU/mL | Standard Deviation 0.08 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 36 | 0 log10 IU/mL | — |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 24 | 0 log10 IU/mL | Standard Deviation 0.01 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 20 | 0 log10 IU/mL | Standard Deviation 0.06 |
| VBR + SOC Nrtl (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 12 | -0.1 log10 IU/mL | Standard Deviation 0.1 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 8 | -1.8 log10 IU/mL | Standard Deviation 0.7 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 20 | -1.2 log10 IU/mL | Standard Deviation 0.96 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 24 | -1.3 log10 IU/mL | Standard Deviation 0.69 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 28 | -1.6 log10 IU/mL | Standard Deviation 0.06 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 4 | -1.8 log10 IU/mL | Standard Deviation 0.75 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 40 | -1.2 log10 IU/mL | — |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 32 | -1.5 log10 IU/mL | — |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 12 | -1.7 log10 IU/mL | Standard Deviation 0.62 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 16 | -1.4 log10 IU/mL | Standard Deviation 0.55 |
| AB-729 + SOC NrtI (Discontinued All) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 36 | -1.2 log10 IU/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 4 | -1.8 log10 IU/mL | Standard Deviation 0.62 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 40 | -2.9 log10 IU/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 24 | -2.9 log10 IU/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 16 | -1.6 log10 IU/mL | Standard Deviation 0.62 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 12 | -2.0 log10 IU/mL | Standard Deviation 0.18 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 28 | -3.0 log10 IU/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 8 | -1.8 log10 IU/mL | Standard Deviation 0.56 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 36 | -3.0 log10 IU/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 44 | -2.8 log10 IU/mL | — |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 20 | -2.1 log10 IU/mL | Standard Deviation 0.28 |
| AB-729 + SOC NrtI (Continued NrtI Only) | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment | Off-Treatment Week 32 | -3.2 log10 IU/mL | — |
Secondary
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.
Population: The number analyzed differs from the overall number analyzed due to early terminated and/or withdrawn subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 20 | -1.7 log10 IU/mL | Standard Deviation 0.55 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 8 | -0.7 log10 IU/mL | Standard Deviation 0.62 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 40 | -1.8 log10 IU/mL | Standard Deviation 0.54 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 24 | -1.7 log10 IU/mL | Standard Deviation 0.52 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 4 | -.3 log10 IU/mL | Standard Deviation 0.35 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 36 | -1.9 log10 IU/mL | Standard Deviation 0.53 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 28 | -1.7 log10 IU/mL | Standard Deviation 0.54 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 52 | -1.8 log10 IU/mL | Standard Deviation 0.53 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 32 | -1.8 log10 IU/mL | Standard Deviation 0.5 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 12 | -1.2 log10 IU/mL | Standard Deviation 0.65 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 2 | -0.3 log10 IU/mL | Standard Deviation 0.42 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 48 | -1.9 log10 IU/mL | Standard Deviation 0.52 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 16 | -1.5 log10 IU/mL | Standard Deviation 0.56 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 56 | -1.5 log10 IU/mL | Standard Deviation 0.35 |
| VBR + AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 44 | -1.9 log10 IU/mL | Standard Deviation 0.54 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 56 | -0.1 log10 IU/mL | Standard Deviation 0.14 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 2 | 0 log10 IU/mL | Standard Deviation 0.07 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 4 | 0 log10 IU/mL | Standard Deviation 0.05 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 8 | 0 log10 IU/mL | Standard Deviation 0.06 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 12 | 0 log10 IU/mL | Standard Deviation 0.07 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 16 | 0 log10 IU/mL | Standard Deviation 0.08 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 20 | 0 log10 IU/mL | Standard Deviation 0.07 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 24 | 0 log10 IU/mL | Standard Deviation 0.07 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 28 | 0 log10 IU/mL | Standard Deviation 0.12 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 32 | 0 log10 IU/mL | Standard Deviation 0.1 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 36 | 0 log10 IU/mL | Standard Deviation 0.11 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 40 | 0 log10 IU/mL | Standard Deviation 0.11 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 44 | 0 log10 IU/mL | Standard Deviation 0.11 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 48 | 0 log10 IU/mL | Standard Deviation 0.12 |
| VBR + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 52 | 0 log10 IU/mL | Standard Deviation 0.09 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 20 | -1.6 log10 IU/mL | Standard Deviation 0.53 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 8 | -0.6 log10 IU/mL | Standard Deviation 0.42 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 40 | -1.8 log10 IU/mL | Standard Deviation 0.5 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 16 | -1.3 log10 IU/mL | Standard Deviation 0.53 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 2 | -0.2 log10 IU/mL | Standard Deviation 0.26 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 44 | -1.9 log10 IU/mL | Standard Deviation 0.47 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 12 | -1.1 log10 IU/mL | Standard Deviation 0.5 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 28 | -1.7 log10 IU/mL | Standard Deviation 0.49 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 4 | -0.3 log10 IU/mL | Standard Deviation 0.39 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 32 | -1.7 log10 IU/mL | Standard Deviation 0.43 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 24 | -1.6 log10 IU/mL | Standard Deviation 0.42 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 48 | -1.9 log10 IU/mL | Standard Deviation 0.51 |
| AB-729 + SOC NrtI | Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment | Week 36 | -1.9 log10 IU/mL | Standard Deviation 0.45 |
Secondary
Number of Participants With HBsAg Seroconversion
Time frame: Week 48
Population: Due to early termination of the study, data was not collected or analyzed for secondary outcomes.
Secondary
Number of Participants With HBV Deoxyribonucleic Acid (DNA) Not Detected (<5 IU/mL)
Time frame: Week 48
Population: Due to early termination of the study, data was not collected or analyzed for secondary outcomes.
Secondary
Number of Participants With HBV Ribonucleic Acid (RNA) <LLOQ
Time frame: Week 48
Population: Due to early termination of the study, data was not collected or analyzed for secondary outcomes.
Secondary
Number of Participants With Normal Alanine Aminotransferase (ALT)
Time frame: Baseline and at pre-specified time points up to 96 weeks
Population: Due to early termination of the study, data was not collected or analyzed for secondary outcomes.
Secondary
Number of Participants With Serum HBsAg Below the Lower Limit of Quantitation (<LLOQ)
Time frame: Pre-specified time points up to 96 weeks
Population: Due to early termination of the study, data was not collected or analyzed for secondary outcomes.
Secondary
Plasma Levels of AB-729
Time frame: 2 hours after dosing at pre-specified time points up to 40 weeks
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
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
Population: Due to early termination of the study, data was not collected or analyzed for secondary outcomes.
Secondary
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
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.