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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: ABI-H2158; Drug: Entecavir (ETV); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincent's Hospital
    • New Lambton, New South Wales, Australia, 2305
      • John Hunter Hospital
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Gallipoli Medical Research Foundation
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
    • Parkville, Victoria, Australia, 3050
      • Melbourne Health
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • (G.I.R.I.) GI Research Institute
  • Ontario
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Centre
• China
  • Changsha, China, 410008
    • Xiangya Hospital Central South University
  • Guangzhou, China, 510515
    • Nanfang Hospital
  • Guangzhou, China
    • Guangzhou Eighth People's Hospital - Guangzhou Infectious Diseases Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Yuzhong District
    • Chongqing, Yuzhong District, China, 400010
      • The Second Affliated Hospital of Chongqing Medical University
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • New Territories
    • Sha Tin, New Territories, Hong Kong
      • Prince of Wales Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 07061
    • SMG-SNU Boramae Medical Center
  • Gangwon-do
    • Chuncheon, Gangwon-do, Korea, Republic of, 24253
      • Hallym University Chuncheon Sacred Heart Hospital
  • Gyeongsangnam-do
    • Yangsan, Gyeongsangnam-do, Korea, Republic of, 50612
      • Pusan National University Yangsan Hospital
• New Zealand
  • Auckland, New Zealand, 2105
    • Auckland Clinical Studies
  • Hamilton, New Zealand, 3240
    • Waikato Hospital
• Taiwan
  • Taichung, Taiwan, 44047
    • China Medical University Hospital
  • Taipei City, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei City, Taiwan, 10449
    • Mackay Memorial Hospital Taipei Branch
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital (CGMH) - Linkou Branch
  • Sanmin District
    • Kaohsiung City, Sanmin District, Taiwan, 80756
      • Kaohsiung Medical University Hospital
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
• United States
  • California
    • Los Angeles, California, United States, 90020
      • Coalition of Inclusive Medicine
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • Redwood City, California, United States, 94063
      • Stanford University Medical Center
    • San Diego, California, United States, 92105
      • Research and Education Inc.
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami/Schiff Center for Liver Diseases
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • New York
    • Flushing, New York, United States, 11355
      • New Discovery, LLC
    • Manhasset, New York, United States, 11030
      • Northwell Health Center for Liver Disease
    • New York, New York, United States, 10016
      • NYU Langone Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Texas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at The Texas Liver Institute
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Assembly Biosciences
• Investigators: Study Director: Grace Wang, Assembly Biosciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 28, 2020
• Primary Completion (ACTUAL): October 14, 2021
• Study Completion (ACTUAL): December 28, 2021

Study Registration Dates

• First Submitted: May 18, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (ACTUAL): May 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 15, 2022
• Last Update Submitted That Met QC Criteria: August 30, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: HBV; hepatitis B
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: ABI-H2158-201; 2019-004902-85 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No