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

Chronic Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04398134
• Other study ID #: ABI-H2158-201
• Secondary ID: 2019-004902-85
• Status: Terminated
• Phase: Phase 2
• Start date: August 28, 2020
• Est. completion date: December 28, 2021

Study information

• Verified date: August 2022
• Source: Assembly Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 88
• Est. completion date: December 28, 2021
• Est. primary completion date: October 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• ABI-H2158
3 X 100 mg tablets for oral administration
• Placebo
Sugar pill manufactured to mimic the ABI-H2158 tablets
• Entecavir (ETV)
0.5 mg tablet for oral administration

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	St. Vincent's Hospital	Darlinghurst	New South Wales
Australia	St. Vincent's Hospital	Fitzroy	Victoria
Australia	Gallipoli Medical Research Foundation	Greenslopes	Queensland
Australia	Alfred Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	New Lambton	New South Wales
Australia	Melbourne Health	Parkville	Victoria
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	(G.I.R.I.) GI Research Institute	Vancouver	British Columbia
China	The First Hospital of Jilin University	Changchun	Jilin
China	Xiangya Hospital Central South University	Changsha
China	The Second Affliated Hospital of Chongqing Medical University	Chongqing	Yuzhong District
China	Guangzhou Eighth People's Hospital - Guangzhou Infectious Diseases Hospital	Guangzhou
China	Nanfang Hospital	Guangzhou
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Sha Tin	New Territories
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Hallym University Chuncheon Sacred Heart Hospital	Chuncheon	Gangwon-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan	Gyeongsangnam-do
New Zealand	Auckland Clinical Studies	Auckland
New Zealand	Waikato Hospital	Hamilton
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung City	Sanmin District
Taiwan	China Medical University Hospital	Taichung
Taiwan	Mackay Memorial Hospital Taipei Branch	Taipei City
Taiwan	National Taiwan University Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital (CGMH) - Linkou Branch	Taoyuan
United Kingdom	King's College Hospital	London
United States	Johns Hopkins University	Baltimore	Maryland
United States	New Discovery, LLC	Flushing	New York
United States	Coalition of Inclusive Medicine	Los Angeles	California
United States	Northwell Health Center for Liver Disease	Manhasset	New York
United States	University of Miami/Schiff Center for Liver Diseases	Miami	Florida
United States	NYU Langone Health	New York	New York
United States	California Liver Research Institute	Pasadena	California
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Stanford University Medical Center	Redwood City	California
United States	American Research Corporation at the Texas Liver Institute	San Antonio	Texas
United States	Research and Education Inc.	San Diego	California
United States	Quest Clinical Research	San Francisco	California
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Assembly Biosciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  Hong Kong,  Korea, Republic of,  New Zealand,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percentage of Participants With Premature Treatment Discontinuation	Describes the number of participants who discontinued treatment with ABI-H2158/placebo prematurely.	Up to 72 weeks
Primary	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
Primary	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	Trough Plasma Concentration of ABI-H2158		Predose on Day 1, Week 4, Week 48, and Week 72
Secondary	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
Secondary	Trough Plasma Concentration of ETV		Predose on Day 1, Week 4, Week 48, and Week 72
Secondary	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
Secondary	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
Secondary	Number of Participants With Reduction in HBV DNA Below the Assay Lower Limit of Quantitation		Up to 72 weeks
Secondary	Number of Participants With Reduction in HBV pgRNA Below the Assay Lower Limit of Quantitation		Up to 72 weeks
Secondary	Change From Baseline in Serum HBV Surface Antigen (HBsAg)		Baseline and up to 72 weeks
Secondary	Change From Baseline in Serum HBV "e" Antigen (HBeAg)		Baseline and up to 72 weeks
Secondary	Change From Baseline in Serum HBV Core-related Antigen (HBcrAg)		Baseline and up to 72 weeks
Secondary	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
Secondary	Ncidence of HBV Variants With Reduced Susceptibility to ABI-H2158		Up to 72 weeks
Secondary	Change in Mean log10 HBV DNA for ABI-H2158+ETV and PBO+ETV at Each Timepoint		up to 72 weeks