A Study Evaluating ABI-H0731 as Adjunctive Therapy in Participants With Chronic Hepatitis B Infection

Study Overview
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Brief Summary
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The purpose of this study is to determine if ABI-H0731 given in combination with a standard of care (SOC) hepatitis B virus (HBV) nucleos(t)ide reverse transcriptase inhibitor (NUC) medication is safe and effective in participants with chronic hepatitis B virus infection (cHBV).

Detailed Description
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This is a Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731 as Adjunctive Therapy in Virally-suppressed Participants with cHBV.

Official Title
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A Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731 as Adjunctive Therapy in Virally-suppressed Patients With Chronic Hepatitis B

Conditions
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Chronic Hepatitis B

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female between ages 18 and 70 years Virologically-suppressed (defined as HBV DNA ≤limit of quantitation (LOQ) for at least 6 months before screening on SOC NUC therapy HBeAg-positive or HBeAg-negative at screening In good general health except for cHBV Key Exclusion Criteria: 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 include: Platelet count <100,000/mm3 Albumin <lower limit of normal (LLN) Direct bilirubin >1.2×upper limit of normal (ULN) Alanine aminotransferase (ALT) >5×ULN at screening 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
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABI-H0731 + SOC NUC<br>Virologically suppressed participants will receive ABI-H0731 along with SOC NUC (ETV, TDF or TAF) 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 ABI-H0731 300 mg tablets orally once daily (QD).<br>Drug: SOC NUC<br>* Participants will continue on their SOC NUC (ETV, TDF or TAF) tablet orally as per approved package insert.<br>* Other names: Tenofovir alafenamide (TAF);|
| Active Comparator: Placebo + SOC NUC<br>Virologically suppressed participants will receive matching placebo tablets and continue their SOC NUC (ETV, TDF or TAF) 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 NUC<br>* Participants will continue on their SOC NUC (ETV, TDF or TAF) tablet orally as per approved package insert.<br>* Other names: Tenofovir alafenamide (TAF);Drug: Placebo Oral Tablet<br>* Participants will receive placebo matching ABI-0731 tablets orally QD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean log10 Serum HBsAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC |  | Baseline to Week 24 | 
| Change in Mean log10 Serum HBeAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC |  | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With 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 + NUC Therapy as Compared With Placebo + NUC Therapy | Abnormal ALT was defined as ≥1.25 x upper limit of normal (34 Units/L for female and 43 Units/L for male participants). | Baseline to Week 24 | 
| Trough Levels of ABI-H0731 on ABI-H0731 + SOC NUC Therapy |  | Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24 | 
| Trough Levels of Entecavir (ETV) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy |  | Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24 | 
| Trough Levels of Tenofovir Alafenamide (TAF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy |  | Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24 | 
| Trough Levels of Tenofovir Disoproxil Fumarate (TDF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy |  | Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24 | 
| Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + SOC NUC Therapy |  | Baseline, Weeks 2, 4, 12, and 24 | 
| Trough to Peak Ratios of SOC NUC on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy |  | Baseline, Weeks 2, 4, 12, and 24 | 

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