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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2a, Multicenter, Single-Blind, Placebo-Controlled, Multiple Cohort Study Evaluating ABI-H2158-Containing Regimens in Chronic Hepatitis B Infection

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: ABI-H2158
* Drug: Placebo
* Drug: Entecavir (ETV)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABI-H2158 plus ETV<br>ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks | Drug: ABI-H2158<br>* 3 X 100 mg tablets for oral administration<br>Drug: Entecavir (ETV)<br>* 0.5 mg tablet for oral administration<br>|
| Placebo Comparator: Placebo plus ETV<br>Placebo matching ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks | Drug: Placebo<br>* Sugar pill manufactured to mimic the ABI-H2158 tablets<br>Drug: Entecavir (ETV)<br>* 0.5 mg tablet for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 72 weeks | 
| Percentage of Participants With Premature Treatment Discontinuation | Describes the number of participants who discontinued treatment with ABI-H2158/placebo prematurely. | Up to 72 weeks | 
| 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. | Baseline and Week 24 | 
| 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. | Up to 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBV, hepatitis B