Chronic Hepatitis B
Conditions
Brief summary
This study will explore the safety and antiviral activity of ABI-H0731 when added to a nucleos(t)ide reverse transcriptase inhibitor (NrtI) in participants who are partially virologically suppressed.
Interventions
Sponsors
Assembly Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 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) * In good general health except for chronic hepatitis B (CHB) * HBeAg positive or HBeAg negative chronic hepatitis B * HBV DNA \>LLOQ using a commercially available assay with LLOQ=20 IU/mL * On a stable NrtI regimen (ETV, TDF or TAF) for more than 12 months * Lack of cirrhosis or advanced liver disease
Exclusion criteria
* Current or prior treatment for CHB with lamivudine, telbivudine, adefovir, HBV core inhibitor, or previous treatment with an investigational agent for HBV infection * Presence of substitutions in the HBV polymerase coding region which may confer reduced susceptibility to NrtIs * Co-infection with human immunodeficiency virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, or hepatitis D virus * Females who are lactating or wish to become pregnant during the course of the trial * History or evidence of advanced liver disease or hepatic decompensation * Clinically significant cardiac disease including poorly-controlled or unstable hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease; liver disease other than CHB; 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 trial participation * History of hepatocellular carcinoma (HCC) * Exclusionary laboratory parameters at Screening: * Platelet count \<100,000/mm\^3 * Albumin \<lower limit of normal * Total bilirubin \>1.2 × upper limit of normal (ULN) * Direct bilirubin \>1.2 × ULN * ALT \>10 × ULN * Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is \>ULN but \<100 ng/mL, the participant is eligible if a hepatic imaging trial prior to initiation of study drug reveals no lesions indicative of possible HCC. * International Normalized Ratio \>1.5 × ULN * Glomerular filtration rate \<50 mL/min/1.73 m\^2 by Chronic Kidney Disease Epidemiology Collaboration equation * Any other laboratory abnormality deemed clinically significant by the Sponsor or the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With an Adverse Event | Baseline and up to 5 months |
| Number of Participants With Premature Discontinuation of Treatment | Baseline and up to 5 months |
| Number of Participants With a Laboratory Abnormality | Baseline and up to 5 months |
| Number of Participants With HBV DNA <Lower Limit of Quantification (LLOQ) at Week 48 | Week 48 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With HBV pgRNA <LLOQ | Baseline and up to 5 months |
| Mean Change From Baseline in log10 Serum Hepatitis B 'e' Antigen (HBeAg) | Baseline and up to 5 months |
| Mean Change From Baseline in log10 Serum Hepatitis B Core-related Antigen (HBcrAg) | Baseline and up to 5 months |
| Mean Change From Baseline in log10 Serum Hepatitis B Surface Antigen (HBsAg) | Baseline and up to 5 months |
| Number of Participants With HBV DNA <Limit of Detection (LOD) | Baseline and up to 5 months |
| Plasma Concentrations of ABI-H0731 | Baseline and up to 5 months |
| Plasma Concentrations of Entecavir | Baseline and up to 5 months |
| Incidence of HBV Variants Among Participants With Evidence of Non-response to Treatment | Baseline and up to 5 months |
| Number of Participants With Normalized Alanine Aminotransferase (ALT) | Baseline and up to 5 months |
| Mean Change From Baseline in log10 HBV DNA | Baseline and up to 5 months |
| Number of Participants With HBV DNA <LLOQ at Each Timepoint | Baseline and up to 5 months |
| Mean Change From Baseline in log10 HBV Pregenomic RNA (pgRNA) | Baseline and up to 5 months |
Countries
Hong Kong, New Zealand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABI-H0731 + SOC NrtI Participants with chronic hepatitis B virus (HBV) infection with partial virologic suppression on NrtI alone will receive ABI-H0731 300 mg once daily plus standard of care (SOC) NrtI for 96 weeks, followed by SOC NrtI alone for an additional 24 weeks (120 weeks total).
ABI-H0731: Participants will receive ABI-H0731 tablets orally once daily
NrtI: Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert | 1 |
| Placebo + SOC NrtI Participants with chronic HBV infection with partial virologic suppression on NrtI alone will receive placebo to ABI-H0731 once daily plus SOC NrtI for 48 weeks, followed by ABI-H0731 300 mg once daily plus SOC NrtI for Weeks 48 to 96, followed by SOC NrtI alone for Weeks 96 to 120.
ABI-H0731: Participants will receive ABI-H0731 tablets orally once daily
Placebo: Participants will receive placebo to ABI-H0731 tablets orally once daily
NrtI: Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study Terminated by Sponsor | 1 | 1 |
Baseline characteristics
| Characteristic | ABI-H0731 + SOC NrtI | Placebo + SOC NrtI | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Baseline ALT (U/L) | 16 U/L | 11 U/L | 13.5 U/L STANDARD_DEVIATION 3.536 |
| Baseline HBcrAg (log10 kU/mL) | 0.89 log10 kU/mL | 0.92 log10 kU/mL | 0.905 log10 kU/mL STANDARD_DEVIATION 0.021 |
| Baseline HBeAg (log10 IU/mL) | 2.35 log10 IU/mL | 2.82 log10 IU/mL | 2.585 log10 IU/mL STANDARD_DEVIATION 0.332 |
| Baseline HBsAg (log10 IU/mL) | 3.81 log10 IU/mL | 4.61 log10 IU/mL | 4.21 log10 IU/mL STANDARD_DEVIATION 0.566 |
| Baseline HBV DNA (Cobas log10 IU/mL) | 2.20 log10 IU/mL | 2.06 log10 IU/mL | 2.13 log10 IU/mL STANDARD_DEVIATION 0.099 |
| Baseline HBV pgRNA (log10 U/mL) | 4.85 log10 U/mL | 6.55 log10 U/mL | 5.7 log10 U/mL STANDARD_DEVIATION 1.202 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Hong Kong | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 0 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Years on HBV treatment at Baseline | 3.6 years | 1.5 years | 2.55 years STANDARD_DEVIATION 1.485 |
| Years positive for HBV | 4.6 years | 45 years | 24.8 years STANDARD_DEVIATION 28.567 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Number of Participants With a Laboratory Abnormality
Time frame: Baseline and up to 5 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABI-H0731 + SOC NrtI | Number of Participants With a Laboratory Abnormality | 1 participants |
| Placebo + SOC NrtI | Number of Participants With a Laboratory Abnormality | 1 participants |
Primary
Number of Participants With an Adverse Event
Time frame: Baseline and up to 5 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABI-H0731 + SOC NrtI | Number of Participants With an Adverse Event | 0 participants |
| Placebo + SOC NrtI | Number of Participants With an Adverse Event | 1 participants |
Primary
Number of Participants With HBV DNA <Lower Limit of Quantification (LLOQ) at Week 48
Time frame: Week 48
Population: Due to early termination of the study, data for Week 48 were not collected and analyzed.
Primary
Number of Participants With Premature Discontinuation of Treatment
Time frame: Baseline and up to 5 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABI-H0731 + SOC NrtI | Number of Participants With Premature Discontinuation of Treatment | 1 participants |
| Placebo + SOC NrtI | Number of Participants With Premature Discontinuation of Treatment | 1 participants |
Secondary
Incidence of HBV Variants Among Participants With Evidence of Non-response to Treatment
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not analyzed for secondary outcomes.
Secondary
Mean Change From Baseline in log10 HBV DNA
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Mean Change From Baseline in log10 HBV Pregenomic RNA (pgRNA)
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not analyzed for secondary outcomes.
Secondary
Mean Change From Baseline in log10 Serum Hepatitis B Core-related Antigen (HBcrAg)
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not analyzed for secondary outcomes.
Secondary
Mean Change From Baseline in log10 Serum Hepatitis B 'e' Antigen (HBeAg)
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not analyzed for secondary outcomes.
Secondary
Mean Change From Baseline in log10 Serum Hepatitis B Surface Antigen (HBsAg)
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not analyzed for secondary outcomes.
Secondary
Number of Participants With HBV DNA <Limit of Detection (LOD)
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not analyzed for secondary outcomes.
Secondary
Number of Participants With HBV DNA <LLOQ at Each Timepoint
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not available to analyze the secondary outcomes.
Secondary
Number of Participants With HBV pgRNA <LLOQ
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not analyzed for secondary outcomes.
Secondary
Number of Participants With Normalized Alanine Aminotransferase (ALT)
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not analyzed for secondary outcomes.
Secondary
Plasma Concentrations of ABI-H0731
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not analyzed for secondary outcomes.
Secondary
Plasma Concentrations of Entecavir
Time frame: Baseline and up to 5 months
Population: Due to early termination of the study, data were not analyzed for secondary outcomes.