Back to resultsA Study of ABI-H2158-containing Regimens in Participants With Chronic Hepatitis B Virus Infection
Primary Purpose
Chronic Hepatitis B
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ABI-H2158
Placebo
Entecavir (ETV)
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B focused on measuring HBV, hepatitis B
Eligibility Criteria
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
Sites / Locations
- Coalition of Inclusive Medicine
- California Liver Research Institute
- Stanford University Medical Center
- Research and Education Inc.
- Quest Clinical Research
- University of Miami/Schiff Center for Liver Diseases
- Johns Hopkins University
- New Discovery, LLC
- Northwell Health Center for Liver Disease
- NYU Langone Health
- Thomas Jefferson University
- American Research Corporation at the Texas Liver Institute
- University of Washington
- Royal Prince Alfred Hospital
- St. Vincent's Hospital
- John Hunter Hospital
- Gallipoli Medical Research Foundation
- St. Vincent's Hospital
- Alfred Hospital
- Melbourne Health
- (G.I.R.I.) GI Research Institute
- Toronto Liver Centre
- The First Hospital of Jilin University
- The Second Affliated Hospital of Chongqing Medical University
- Xiangya Hospital Central South University
- Nanfang Hospital
- Guangzhou Eighth People's Hospital - Guangzhou Infectious Diseases Hospital
- Prince of Wales Hospital
- Queen Mary Hospital
- Hallym University Chuncheon Sacred Heart Hospital
- Pusan National University Yangsan Hospital
- Pusan National University Hospital
- Seoul National University Hospital
- Severance Hospital, Yonsei University Health System
- Asan Medical Center
- SMG-SNU Boramae Medical Center
- Auckland Clinical Studies
- Waikato Hospital
- Kaohsiung Medical University Hospital
- China Medical University Hospital
- National Taiwan University Hospital
- Mackay Memorial Hospital Taipei Branch
- Chang Gung Memorial Hospital (CGMH) - Linkou Branch
- King's College Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ABI-H2158 plus ETV
Placebo plus ETV
Arm Description
ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
Placebo matching ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
Outcomes
Primary Outcome Measures
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.
Percentage of Participants With Premature Treatment Discontinuation
Describes the number of participants who discontinued treatment with ABI-H2158/placebo prematurely.
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.
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.
Secondary Outcome Measures
Trough Plasma Concentration of ABI-H2158
Trough-to-Peak Plasma Concentration Ratio of ABI-H2158
Trough Plasma Concentration of ETV
Trough-to-Peak Plasma Concentration Ratio of ETV
Change in Mean log10 HBV pgRNA From Baseline to Week 24 and at Each Timepoint for ABI-H2158+ETV and PBO+ETV
Number of Participants With Reduction in HBV DNA Below the Assay Lower Limit of Quantitation
Number of Participants With Reduction in HBV pgRNA Below the Assay Lower Limit of Quantitation
Change From Baseline in Serum HBV Surface Antigen (HBsAg)
Change From Baseline in Serum HBV "e" Antigen (HBeAg)
Change From Baseline in Serum HBV Core-related Antigen (HBcrAg)
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
Ncidence of HBV Variants With Reduced Susceptibility to ABI-H2158
Change in Mean log10 HBV DNA for ABI-H2158+ETV and PBO+ETV at Each Timepoint
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04398134
Brief Title
A Study of ABI-H2158-containing Regimens in Participants With Chronic Hepatitis B Virus Infection
Official Title
A Phase 2a, Multicenter, Single-Blind, Placebo-Controlled, Multiple Cohort Study Evaluating ABI-H2158-Containing Regimens in Chronic Hepatitis B Infection
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
Study stopped due to a safety signal of drug-induced liver injury in subjects receiving 2158
Study Start Date
August 28, 2020 (Actual)
Primary Completion Date
October 14, 2021 (Actual)
Study Completion Date
December 28, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assembly Biosciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
HBV, hepatitis B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
88 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ABI-H2158 plus ETV
Arm Type
Experimental
Arm Description
ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
Arm Title
Placebo plus ETV
Arm Type
Placebo Comparator
Arm Description
Placebo matching ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
Intervention Type
Drug
Intervention Name(s)
ABI-H2158
Intervention Description
3 X 100 mg tablets for oral administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Sugar pill manufactured to mimic the ABI-H2158 tablets
Intervention Type
Drug
Intervention Name(s)
Entecavir (ETV)
Intervention Description
0.5 mg tablet for oral administration
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events
Description
Describes the number of participants with One or More Adverse Events while they were on treatment with the study drug.
Time Frame
Up to 72 weeks
Title
Percentage of Participants With Premature Treatment Discontinuation
Description
Describes the number of participants who discontinued treatment with ABI-H2158/placebo prematurely.
Time Frame
Up to 72 weeks
Title
Change From Baseline in Mean log10 HBV DNA
Description
HBV DNA was measured by Cobas AmpliPrep/ Cobas TaqMan HBV Test v2.0 (LOD 10 IU/mL). The analysis of data was descriptive only.
Time Frame
Baseline and Week 24
Title
Percentage of Participants With Abnormal Laboratory Results
Description
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.
Time Frame
Up to 72 weeks
Secondary Outcome Measure Information:
Title
Trough Plasma Concentration of ABI-H2158
Time Frame
Predose on Day 1, Week 4, Week 48, and Week 72
Title
Trough-to-Peak Plasma Concentration Ratio of ABI-H2158
Time Frame
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
Title
Trough Plasma Concentration of ETV
Time Frame
Predose on Day 1, Week 4, Week 48, and Week 72
Title
Trough-to-Peak Plasma Concentration Ratio of ETV
Time Frame
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
Title
Change in Mean log10 HBV pgRNA From Baseline to Week 24 and at Each Timepoint for ABI-H2158+ETV and PBO+ETV
Time Frame
up to Week 72
Title
Number of Participants With Reduction in HBV DNA Below the Assay Lower Limit of Quantitation
Time Frame
Up to 72 weeks
Title
Number of Participants With Reduction in HBV pgRNA Below the Assay Lower Limit of Quantitation
Time Frame
Up to 72 weeks
Title
Change From Baseline in Serum HBV Surface Antigen (HBsAg)
Time Frame
Baseline and up to 72 weeks
Title
Change From Baseline in Serum HBV "e" Antigen (HBeAg)
Time Frame
Baseline and up to 72 weeks
Title
Change From Baseline in Serum HBV Core-related Antigen (HBcrAg)
Time Frame
Baseline and up to 72 weeks
Title
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
Time Frame
Baseline and up to Week 24
Title
Ncidence of HBV Variants With Reduced Susceptibility to ABI-H2158
Time Frame
Up to 72 weeks
Title
Change in Mean log10 HBV DNA for ABI-H2158+ETV and PBO+ETV at Each Timepoint
Time Frame
up to 72 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Grace Wang
Organizational Affiliation
Assembly Biosciences
Official's Role
Study Director
Facility Information:
Facility Name
Coalition of Inclusive Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90020
Country
United States
Facility Name
California Liver Research Institute
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
Stanford University Medical Center
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Facility Name
Research and Education Inc.
City
San Diego
State/Province
California
ZIP/Postal Code
92105
Country
United States
Facility Name
Quest Clinical Research
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
University of Miami/Schiff Center for Liver Diseases
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
New Discovery, LLC
City
Flushing
State/Province
New York
ZIP/Postal Code
11355
Country
United States
Facility Name
Northwell Health Center for Liver Disease
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
American Research Corporation at the Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
St. Vincent's Hospital
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
John Hunter Hospital
City
New Lambton
State/Province
New South Wales
ZIP/Postal Code
2305
Country
Australia
Facility Name
Gallipoli Medical Research Foundation
City
Greenslopes
State/Province
Queensland
ZIP/Postal Code
4120
Country
Australia
Facility Name
St. Vincent's Hospital
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Melbourne Health
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
(G.I.R.I.) GI Research Institute
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2K5
Country
Canada
Facility Name
Toronto Liver Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6H 3M1
Country
Canada
Facility Name
The First Hospital of Jilin University
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
The Second Affliated Hospital of Chongqing Medical University
City
Chongqing
State/Province
Yuzhong District
ZIP/Postal Code
400010
Country
China
Facility Name
Xiangya Hospital Central South University
City
Changsha
ZIP/Postal Code
410008
Country
China
Facility Name
Nanfang Hospital
City
Guangzhou
ZIP/Postal Code
510515
Country
China
Facility Name
Guangzhou Eighth People's Hospital - Guangzhou Infectious Diseases Hospital
City
Guangzhou
Country
China
Facility Name
Prince of Wales Hospital
City
Sha Tin
State/Province
New Territories
Country
Hong Kong
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Hallym University Chuncheon Sacred Heart Hospital
City
Chuncheon
State/Province
Gangwon-do
ZIP/Postal Code
24253
Country
Korea, Republic of
Facility Name
Pusan National University Yangsan Hospital
City
Yangsan
State/Province
Gyeongsangnam-do
ZIP/Postal Code
50612
Country
Korea, Republic of
Facility Name
Pusan National University Hospital
City
Busan
ZIP/Postal Code
49241
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
SMG-SNU Boramae Medical Center
City
Seoul
ZIP/Postal Code
07061
Country
Korea, Republic of
Facility Name
Auckland Clinical Studies
City
Auckland
ZIP/Postal Code
2105
Country
New Zealand
Facility Name
Waikato Hospital
City
Hamilton
ZIP/Postal Code
3240
Country
New Zealand
Facility Name
Kaohsiung Medical University Hospital
City
Kaohsiung City
State/Province
Sanmin District
ZIP/Postal Code
80756
Country
Taiwan
Facility Name
China Medical University Hospital
City
Taichung
ZIP/Postal Code
44047
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei City
ZIP/Postal Code
100
Country
Taiwan
Facility Name
Mackay Memorial Hospital Taipei Branch
City
Taipei City
ZIP/Postal Code
10449
Country
Taiwan
Facility Name
Chang Gung Memorial Hospital (CGMH) - Linkou Branch
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan
Facility Name
King's College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of ABI-H2158-containing Regimens in Participants With Chronic Hepatitis B Virus Infection
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