A Study Evaluating Treatment Intensification With ABI-H0731 in Participants With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2a, Multi-Center, Single-Blind, Placebo-Controlled Study Evaluating Treatment Intensification With ABI-H0731 in Subjects With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: ABI-H0731
* Drug: Placebo
* Drug: NrtI


Participation Criteria
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Eligibility Criteria
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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.

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-H0731 + SOC NrtI<br>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). | Drug: ABI-H0731<br>* Participants will receive ABI-H0731 tablets orally once daily<br>Drug: NrtI<br>* Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert<br>* Other names: Nucleos(t)ide reverse transcriptase inhibitor;|
| Placebo Comparator: Placebo + SOC NrtI<br>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. | Drug: ABI-H0731<br>* Participants will receive ABI-H0731 tablets orally once daily<br>Drug: Placebo<br>* Participants will receive placebo to ABI-H0731 tablets orally once daily<br>Drug: NrtI<br>* Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert<br>* Other names: Nucleos(t)ide reverse transcriptase inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Number of Participants With HBV DNA <Limit of Detection (LOD) |  | Baseline and up to 5 months | 
| Mean Change From Baseline in log10 HBV Pregenomic RNA (pgRNA) |  | Baseline and up to 5 months | 
| 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 Normalized Alanine Aminotransferase (ALT) |  | 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 |