A Study of ABI-H2158-containing Regimens in Participants With Chronic Hepatitis B Virus Infection

Phase 2

Terminated

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
ABI-H2158 plus ETV	ABI-H2158	ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
ABI-H2158 plus ETV	Entecavir (ETV)	ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
Placebo plus ETV	Placebo	Placebo matching ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
Placebo plus ETV	Entecavir (ETV)	Placebo matching ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Trough Plasma Concentration of ABI-H2158	Predose on Day 1, Week 4, Week 48, and Week 72
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
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
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
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

Locations (43): Coalition of Inclusive Medicine
🇺🇸
Los Angeles, California, United States
California Liver Research Institute
🇺🇸
Pasadena, California, United States
Stanford University Medical Center
🇺🇸
Redwood City, California, United States
Research and Education Inc.
🇺🇸
San Diego, California, United States
Quest Clinical Research
🇺🇸
San Francisco, California, United States
University of Miami/Schiff Center for Liver Diseases
🇺🇸
Miami, Florida, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
New Discovery, LLC
🇺🇸
Flushing, New York, United States
Northwell Health Center for Liver Disease
🇺🇸
Manhasset, New York, United States
NYU Langone Health
🇺🇸
New York, New York, United States
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Coalition of Inclusive Medicine
🇺🇸Los Angeles, California, United States