A Study of ABI-H2158-containing Regimens in Participants With Chronic Hepatitis B Virus Infection
- Conditions
- Chronic Hepatitis B
- Interventions
- Registration Number
- NCT04398134
- Lead Sponsor
- Assembly Biosciences
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 88
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ABI-H2158 plus ETV ABI-H2158 ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks ABI-H2158 plus ETV Entecavir (ETV) ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks Placebo plus ETV Placebo Placebo matching ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks Placebo plus ETV Entecavir (ETV) Placebo matching ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
- Primary Outcome Measures
Name Time Method Percentage of Participants With Adverse Events Up to 72 weeks Describes the number of participants with One or More Adverse Events while they were on treatment with the study drug.
Percentage of Participants With Premature Treatment Discontinuation Up to 72 weeks Describes the number of participants who discontinued treatment with ABI-H2158/placebo prematurely.
Change From Baseline in Mean log10 HBV DNA Baseline and Week 24 HBV DNA was measured by Cobas AmpliPrep/ Cobas TaqMan HBV Test v2.0 (LOD 10 IU/mL). The analysis of data was descriptive only.
Percentage of Participants With Abnormal Laboratory Results Up to 72 weeks 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.
- Secondary Outcome Measures
Name Time Method 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 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 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
Trial Locations
- Locations (43)
Toronto Liver Centre
🇨🇦Toronto, Ontario, Canada
John Hunter Hospital
🇦🇺New Lambton, New South Wales, Australia
Research and Education Inc.
🇺🇸San Diego, California, United States
University of Miami/Schiff Center for Liver Diseases
🇺🇸Miami, Florida, United States
American Research Corporation at the Texas Liver Institute
🇺🇸San Antonio, Texas, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Hallym University Chuncheon Sacred Heart Hospital
🇰🇷Chuncheon, Gangwon-do, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Northwell Health Center for Liver Disease
🇺🇸Manhasset, New York, United States
Quest Clinical Research
🇺🇸San Francisco, California, United States
Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Chang Gung Memorial Hospital (CGMH) - Linkou Branch
🇨🇳Taoyuan, Taiwan
California Liver Research Institute
🇺🇸Pasadena, California, United States
Coalition of Inclusive Medicine
🇺🇸Los Angeles, California, United States
St. Vincent's Hospital
🇦🇺Fitzroy, Victoria, Australia
SMG-SNU Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
New Discovery, LLC
🇺🇸Flushing, New York, United States
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung City, Sanmin District, Taiwan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Waikato Hospital
🇳🇿Hamilton, New Zealand
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Gallipoli Medical Research Foundation
🇦🇺Greenslopes, Queensland, Australia
NYU Langone Health
🇺🇸New York, New York, United States
University of Washington
🇺🇸Seattle, Washington, United States
China Medical University Hospital
🇨🇳Taichung, Taiwan
Mackay Memorial Hospital Taipei Branch
🇨🇳Taipei City, Taiwan
King's College Hospital
🇬🇧London, United Kingdom
Pusan National University Yangsan Hospital
🇰🇷Yangsan, Gyeongsangnam-do, Korea, Republic of
Auckland Clinical Studies
🇳🇿Auckland, New Zealand
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
The Second Affliated Hospital of Chongqing Medical University
🇨🇳Chongqing, Yuzhong District, China
Xiangya Hospital Central South University
🇨🇳Changsha, China
Guangzhou Eighth People's Hospital - Guangzhou Infectious Diseases Hospital
🇨🇳Guangzhou, China
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Stanford University Medical Center
🇺🇸Redwood City, California, United States
Nanfang Hospital
🇨🇳Guangzhou, China
Melbourne Health
🇦🇺Parkville, Victoria, Australia
(G.I.R.I.) GI Research Institute
🇨🇦Vancouver, British Columbia, Canada
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Prince of Wales Hospital
🇭🇰Sha Tin, New Territories, Hong Kong