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

Phase 2

Completed

Conditions: Chronic Hepatitis B

Interventions: Drug: ABI-H0731
Drug: SOC ETV
Drug: Placebo Oral Tablet

Registration Number: NCT03577171

Lead Sponsor: Assembly Biosciences

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ABI-H0731 + SOC ETV	SOC ETV	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.
ABI-H0731 + SOC ETV	ABI-H0731	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.
Placebo + SOC ETV	Placebo Oral Tablet	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.
Placebo + SOC ETV	SOC ETV	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.

Primary Outcome Measures

Name	Time	Method
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	Baseline, Week 12, and Week 24	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.

Secondary Outcome Measures

Name	Time	Method
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	Baseline and up to Week 24	Vital signs assessed were body temperature, respiratory rate, and pulse rate
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	Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24	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.
Median Time to Viral Suppression, Defined as HBV DNA <20 IU/mL, on ABI-H0731 + ETV as Compared to Placebo + ETV	Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24	Median time to viral suppression will be calculated and evaluated between participants on ABI-H0731 + ETV as compared to placebo + ETV.
Number of Participants With Emergence of Resistant HBV Variants on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV	Up to Week 36	Emergence of a resistant HBV variant was defined as an increase of ≥1 log10 IU/mL from the nadir in HBV DNA.
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

Trial Locations

Locations (12): Waikato Hospital
🇳🇿
Hamilton, New Zealand
King's College London
🇬🇧
London, United Kingdom
Southern California Research Center
🇺🇸
Coronado, California, United States
Asia Pacific Liver Center
🇺🇸
Los Angeles, California, United States
Johns Hopkins University School of Medicine
🇺🇸
Baltimore, Maryland, United States
Research and Education
🇺🇸
San Diego, California, United States
Xiaoli Ma MD
🇺🇸
Philadelphia, Pennsylvania, United States
Toronto Liver Center
🇨🇦
Toronto, Ontario, Canada
GI Research Institute
🇨🇦
Vancouver, British Columbia, Canada
NYU Langone Health
🇺🇸
New York, New York, United States
Quest Clinical Research
🇺🇸
San Francisco, California, United States
University of Hong Kong, Queen Mary Hospital
🇭🇰
Hong Kong, Hong Kong