A Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Participants With Chronic Hepatitis B Virus Infection (cHBV)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if ABI-H0731 given in combination with a standard of care (SOC) entecavir (ETV) is safe and effective in participants with chronic hepatitis B infection (cHBV)

Detailed Description
-----------------
This is a Phase 2a, multi-center, double-blind, placebo-controlled study evaluating ABI-H0731+ ETV vs ETV alone for the treatment of viremic hepatitis B e antigen (HBeAg)-positive participants with cHBV.

Official Title
-----------------
A Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Patients With Chronic Hepatitis B

Conditions
-----------------
Chronic Hepatitis B

Intervention / Treatment
-----------------
* Drug: ABI-H0731
* Drug: SOC ETV
* Drug: Placebo Oral Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Male or female between ages 18 and 70 years HBeAg-positive at screening In good general health except for cHBV HBV viral load ≥2×105 IU/mL Hepatitis B surface antigen (HBsAg) >1000 IU/mL at screening Key Exclusion Criteria: Any prior treatment with lamivudine or telbivudine, previous treatment with an investigational agent for HBV other than ABI-H0731; or any other SOC treatment for >4 weeks Co-infection with HIV, hepatitis C virus (HCV), hepatitis E virus (HEV) or hepatitis D virus (HDV) History or evidence of hepatic decompensation (including gastrointestinal bleeding or esophageal varices) at any time prior to or at time of screening Clinically significant cardiac or pulmonary disease, chronic or recurrent renal or urinary tract disease, liver disease other than HBV, endocrine disorder, autoimmune disorder, diabetes mellitus requiring treatment with insulin or hypoglycemic agents, neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment, 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 participant unsuitable for the study Previous treatment with an investigational agent for HBV other than ABI-H0731 in the last 6 months before screening History of hepatocellular carcinoma (HCC) Females who are lactating or pregnant or wish to become pregnant are excluded from the study Exclusionary laboratory parameters at screening: Platelet count <100,000/mm3 Albumin <lower limit of normal (LLN) Direct bilirubin >1.2×upper limit of normal (ULN) Alanine aminotransferase (ALT) >10×ULN at screening Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is >ULN but <100 ng/mL, participant is eligible if a hepatic imaging study prior to the initiation of study drug reveals no lesions suspicious of possible HCC International Normalized Ratio (INR) >1.5×ULN Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABI-H0731 + SOC ETV<br>Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. | Drug: ABI-H0731<br>* Participants will receive 300mg QD of ABI-H0731 tablets orally.<br>Drug: SOC ETV<br>* Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.<br>* Other names: Entecavir;|
| Experimental: Placebo + SOC ETV<br>Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. | Drug: SOC ETV<br>* Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.<br>* Other names: Entecavir;Drug: Placebo Oral Tablet<br>* Participants will receive matching QD placebo tablets orally.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean log10 HBV DNA From Baseline (Day 1) to Week 12 or Week 24 on ABI H0731 + SOC ETV as Compared to Placebo + SOC ETV | Hepatitis B virus (HBV) DNA was measured using COBAS TaqMan Version 2.0. The lower limit of quantitation (LLOQ) was 20 IU/mL and the limit of detection (LOD) was 10 IU/mL. | Baseline, Week 12, and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants One or More Adverse Events |  | Up to Follow-up (maximum up to Week 36) | 
| Number of Participants With Premature Study Discontinuation |  | Up to Follow-up (maximum up to Week 36) | 
| Number of Participants With One or More Abnormal Safety Laboratory Result |  | Up to Week 36 | 
| Number of Participants With a Clinically-significant Electrocardiogram Abnormality |  | Up to Week 24 | 
| Number of Participants With a Clinically-significant Change in Vital Signs | Vital signs assessed were body temperature, respiratory rate, and pulse rate | Baseline and up to Week 24 | 
| Number of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at Week 24 on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV |  | Baseline to Week 24 | 
| Number of Participants With a Decline in Viral DNA to Below Limit of Quantitation on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV | HBV DNA was measured using COBAS TaqMan Version 2.0. The LLOQ was 20 IU/mL and the LOD was 10 IU/mL. The number of participants with HBV DNA below the limit of quantitation (<20 IU/mL) and target detected (≥10 IU/mL) was assessed. | Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 | 
| Median Time to Viral Suppression, Defined as HBV DNA <20 IU/mL, on ABI-H0731 + ETV as Compared to Placebo + ETV | Median time to viral suppression will be calculated and evaluated between participants on ABI-H0731 + ETV as compared to placebo + ETV. | Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 | 
| Number of Participants With Emergence of Resistant HBV Variants on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV | Emergence of a resistant HBV variant was defined as an increase of ≥1 log10 IU/mL from the nadir in HBV DNA. | Up to Week 36 | 
| Trough Levels of ABI-H0731 on ABI-H0731 + SOC ETV Therapy |  | Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24 | 
| Trough Levels of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy |  | Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24 | 
| Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + ETV Therapy |  | Baseline, Weeks 2, 4, 12, and 24 | 
| Trough to Peak Ratios of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy |  | Baseline, Weeks 2, 4, 12, 24, and 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cHBV, HBV, HBeAg-positive, hepatitis B, vebicorvir, VBR