Chronic Hepatitis B
Conditions
Keywords
HBV, hepatitis B
Brief summary
This Phase 2a study will assess the safety, antiviral activity, and pharmacokinetics (PK) of ABI-H2158 administered once daily for up to 72 weeks in combination with entecavir (ETV) in participants with chronic hepatitis B virus (HBV) infection.
Interventions
DRUGABI-H2158
3 X 100 mg tablets for oral administration
DRUGPlacebo
Sugar pill manufactured to mimic the ABI-H2158 tablets
DRUGEntecavir (ETV)
0.5 mg tablet for oral administration
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 of 18 - 36 kg/m\^2 and body weight ≥45 kg * HBeAg ≥500 IU/mL at Screening * In good general health except for chronic HBV infection for ≥6 months documented, for example, by at least two measurements of HBsAg positivity and/or detectable HBV DNA ≥6 months apart * Lack of cirrhosis or advanced liver disease
Exclusion criteria
* Prior treatment for chronic HBV infection with lamivudine, telbivudine, adefovir, standard of care nucleoside or nucleotide analogue (NrtI), HBV core inhibitors, or an investigational agent for HBV infection * History or evidence of advanced liver disease or hepatic decompensation (including jaundice, ascites, portal hypertension, gastrointestinal bleeding, esophageal varices, hepatic encephalopathy) * History or presence of clinically significant medical conditions requiring frequent medical management or pharmacologic or surgical treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events | Up to 72 weeks | Describes the number of participants with One or More Adverse Events while they were on treatment with the study drug. |
| Percentage of Participants With Premature Treatment Discontinuation | Up to 72 weeks | Describes the number of participants who discontinued treatment with ABI-H2158/placebo prematurely. |
| Change From Baseline in Mean log10 HBV DNA | Baseline and Week 24 | HBV DNA was measured by Cobas AmpliPrep/ Cobas TaqMan HBV Test v2.0 (LOD 10 IU/mL). The analysis of data was descriptive only. |
| Percentage of Participants With Abnormal Laboratory Results | Up to 72 weeks | Severity grades were defined by Grading Scale for Severity of Adverse Events and Laboratory Abnormalities \[The DAIDS Version 2.1\]. For maximum postbaseline toxicity grade, the most severe graded abnormality from all tests was counted for each participant. For each individual laboratory test, the most severe graded abnormality for that test was counted for a participant. A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the date of last dose of ABI-H2158/Placebo plus 28 days. |
Secondary
| Measure | Time frame |
|---|---|
| Change in Mean log10 HBV pgRNA From Baseline to Week 24 and at Each Timepoint for ABI-H2158+ETV and PBO+ETV | up to Week 72 |
| Number of Participants With Reduction in HBV DNA Below the Assay Lower Limit of Quantitation | Up to 72 weeks |
| Number of Participants With Reduction in HBV pgRNA Below the Assay Lower Limit of Quantitation | Up to 72 weeks |
| Change From Baseline in Serum HBV Surface Antigen (HBsAg) | Baseline and up to 72 weeks |
| Trough Plasma Concentration of ABI-H2158 | Predose on Day 1, Week 4, Week 48, and Week 72 |
| Change From Baseline in Serum HBV Core-related Antigen (HBcrAg) | Baseline and up to 72 weeks |
| Proportion of Subjects With Abnormal ALT at Baseline Who Have Normal ALT at Week 24 and at Each Timepoint on ABI-H2158+ETV and PBO+ETV | Baseline and up to Week 24 |
| Ncidence of HBV Variants With Reduced Susceptibility to ABI-H2158 | Up to 72 weeks |
| Change in Mean log10 HBV DNA for ABI-H2158+ETV and PBO+ETV at Each Timepoint | up to 72 weeks |
| Change From Baseline in Serum HBV e Antigen (HBeAg) | Baseline and up to 72 weeks |
| Trough-to-Peak Plasma Concentration Ratio of ABI-H2158 | Predose on Day 1 and Weeks 4, 48, and 72 and at pre-specified intervals after dosing on Day 1 and Weeks 2, 8, 12, 16, 20, 24, and 28 |
| Trough Plasma Concentration of ETV | Predose on Day 1, Week 4, Week 48, and Week 72 |
| Trough-to-Peak Plasma Concentration Ratio of ETV | Predose on Day 1 and Weeks 4, 48, and 72 and at pre-specified intervals after dosing on Day 1 and Weeks 2, 8, 12, 16, 20, 24, and 28 |
Countries
Australia, Canada, China, Hong Kong, New Zealand, South Korea, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABI-H2158 Plus ETV (HBeAg Positive Population) ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
ABI-H2158: 3 X 100 mg tablets for oral administration
Entecavir (ETV): 0.5 mg tablet for oral administration | 32 |
| Placebo Plus ETV (HBeAg Positive Population) Placebo matching ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
Placebo: Sugar pill manufactured to mimic the ABI-H2158 tablets
Entecavir (ETV): 0.5 mg tablet for oral administration | 11 |
| ABI-H2158 Plus ETV (HBeAg Negative Population) ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
ABI-H2158: 3 X 100 mg tablets for oral administration
Entecavir (ETV): 0.5 mg tablet for oral administration | 33 |
| Placebo Plus ETV (HBeAg Negative Population) Placebo matching ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
Placebo: Sugar pill manufactured to mimic the ABI-H2158 tablets
Entecavir (ETV): 0.5 mg tablet for oral administration | 12 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Study Terminated by Sponsor | 30 | 11 | 32 | 11 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | ABI-H2158 Plus ETV (HBeAg Positive Population) | Total | Placebo Plus ETV (HBeAg Negative Population) | ABI-H2158 Plus ETV (HBeAg Negative Population) | Placebo Plus ETV (HBeAg Positive Population) |
|---|---|---|---|---|---|
| Age, Continuous | 37 years STANDARD_DEVIATION 8.3 | 41 years STANDARD_DEVIATION 10.3 | 46 years STANDARD_DEVIATION 9.8 | 44 years STANDARD_DEVIATION 11 | 35 years STANDARD_DEVIATION 9.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 32 Participants | 85 Participants | 12 Participants | 31 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Canada | 0 participants | 4 participants | 1 participants | 3 participants | 0 participants |
| Region of Enrollment China | 6 participants | 22 participants | 4 participants | 10 participants | 2 participants |
| Region of Enrollment Hong Kong | 8 participants | 19 participants | 3 participants | 5 participants | 3 participants |
| Region of Enrollment New Zealand | 1 participants | 3 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment South Korea | 4 participants | 7 participants | 0 participants | 3 participants | 0 participants |
| Region of Enrollment Taiwan | 4 participants | 9 participants | 1 participants | 3 participants | 1 participants |
| Region of Enrollment United Kingdom | 1 participants | 3 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment United States | 8 participants | 21 participants | 3 participants | 8 participants | 2 participants |
| Sex: Female, Male Female | 13 Participants | 40 Participants | 8 Participants | 13 Participants | 6 Participants |
| Sex: Female, Male Male | 19 Participants | 48 Participants | 4 Participants | 20 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 11 | 0 / 33 | 0 / 12 |
| other Total, other adverse events | 18 / 32 | 6 / 11 | 19 / 33 | 6 / 12 |
| serious Total, serious adverse events | 1 / 32 | 1 / 11 | 0 / 33 | 1 / 12 |
Outcome results
Primary
Change From Baseline in Mean log10 HBV DNA
HBV DNA was measured by Cobas AmpliPrep/ Cobas TaqMan HBV Test v2.0 (LOD 10 IU/mL). The analysis of data was descriptive only.
Time frame: Baseline and Week 24
Population: Due to early termination of the study, samples at Week 24 from participants in the HBeAg negative cohort were not collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABI-H2158 Plus ETV (HBeAg Positive Population) | Change From Baseline in Mean log10 HBV DNA | -6.2 log10 IU/mL | Standard Deviation 0.76 |
| Placebo Plus ETV (HBeAg Positive Population) | Change From Baseline in Mean log10 HBV DNA | -4.8 log10 IU/mL | Standard Deviation 0.25 |
Primary
Percentage of Participants With Abnormal Laboratory Results
Severity grades were defined by Grading Scale for Severity of Adverse Events and Laboratory Abnormalities \[The DAIDS Version 2.1\]. For maximum postbaseline toxicity grade, the most severe graded abnormality from all tests was counted for each participant. For each individual laboratory test, the most severe graded abnormality for that test was counted for a participant. A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the date of last dose of ABI-H2158/Placebo plus 28 days.
Time frame: Up to 72 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABI-H2158 Plus ETV (HBeAg Positive Population) | Percentage of Participants With Abnormal Laboratory Results | 29 Participants |
| Placebo Plus ETV (HBeAg Positive Population) | Percentage of Participants With Abnormal Laboratory Results | 8 Participants |
| ABI-H2158 Plus ETV (HBeAg Negative Population) | Percentage of Participants With Abnormal Laboratory Results | 19 Participants |
| Placebo Plus ETV (HBeAg Negative Population) | Percentage of Participants With Abnormal Laboratory Results | 9 Participants |
Primary
Percentage of Participants With Adverse Events
Describes the number of participants with One or More Adverse Events while they were on treatment with the study drug.
Time frame: Up to 72 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABI-H2158 Plus ETV (HBeAg Positive Population) | Percentage of Participants With Adverse Events | 18 Participants |
| Placebo Plus ETV (HBeAg Positive Population) | Percentage of Participants With Adverse Events | 6 Participants |
| ABI-H2158 Plus ETV (HBeAg Negative Population) | Percentage of Participants With Adverse Events | 19 Participants |
| Placebo Plus ETV (HBeAg Negative Population) | Percentage of Participants With Adverse Events | 6 Participants |
Primary
Percentage of Participants With Premature Treatment Discontinuation
Describes the number of participants who discontinued treatment with ABI-H2158/placebo prematurely.
Time frame: Up to 72 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABI-H2158 Plus ETV (HBeAg Positive Population) | Percentage of Participants With Premature Treatment Discontinuation | 2 Participants |
| Placebo Plus ETV (HBeAg Positive Population) | Percentage of Participants With Premature Treatment Discontinuation | 0 Participants |
| ABI-H2158 Plus ETV (HBeAg Negative Population) | Percentage of Participants With Premature Treatment Discontinuation | 2 Participants |
| Placebo Plus ETV (HBeAg Negative Population) | Percentage of Participants With Premature Treatment Discontinuation | 0 Participants |
Secondary
Change From Baseline in Serum HBV Core-related Antigen (HBcrAg)
Time frame: Baseline and up to 72 weeks
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Change From Baseline in Serum HBV e Antigen (HBeAg)
Time frame: Baseline and up to 72 weeks
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Change From Baseline in Serum HBV Surface Antigen (HBsAg)
Time frame: Baseline and up to 72 weeks
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Change in Mean log10 HBV DNA for ABI-H2158+ETV and PBO+ETV at Each Timepoint
Time frame: up to 72 weeks
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Change in Mean log10 HBV pgRNA From Baseline to Week 24 and at Each Timepoint for ABI-H2158+ETV and PBO+ETV
Time frame: up to Week 72
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Ncidence of HBV Variants With Reduced Susceptibility to ABI-H2158
Time frame: Up to 72 weeks
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Number of Participants With Reduction in HBV DNA Below the Assay Lower Limit of Quantitation
Time frame: Up to 72 weeks
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Number of Participants With Reduction in HBV pgRNA Below the Assay Lower Limit of Quantitation
Time frame: Up to 72 weeks
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Proportion of Subjects With Abnormal ALT at Baseline Who Have Normal ALT at Week 24 and at Each Timepoint on ABI-H2158+ETV and PBO+ETV
Time frame: Baseline and up to Week 24
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Trough Plasma Concentration of ABI-H2158
Time frame: Predose on Day 1, Week 4, Week 48, and Week 72
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Trough Plasma Concentration of ETV
Time frame: Predose on Day 1, Week 4, Week 48, and Week 72
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Trough-to-Peak Plasma Concentration Ratio of ABI-H2158
Time frame: Predose on Day 1 and Weeks 4, 48, and 72 and at pre-specified intervals after dosing on Day 1 and Weeks 2, 8, 12, 16, 20, 24, and 28
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.
Secondary
Trough-to-Peak Plasma Concentration Ratio of ETV
Time frame: Predose on Day 1 and Weeks 4, 48, and 72 and at pre-specified intervals after dosing on Day 1 and Weeks 2, 8, 12, 16, 20, 24, and 28
Population: Due to early termination of the study, data were not collected and analyzed for secondary outcomes.