Clinical trial NCT04398134: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: HBV
hepatitis B
Lead sponsor: Assembly Biosciences
Sponsor class: INDUSTRY
First posted: 2020-05-21
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Up to 72 weeks
measure: Percentage of Participants With Premature Treatment Discontinuation
timeFrame: Up to 72 weeks
measure: Change From Baseline in Mean log10 HBV DNA
timeFrame: Baseline and Week 24
measure: Percentage of Participants With Abnormal Laboratory Results
timeFrame: Up to 72 weeks
Secondary outcomes:
measure: Trough Plasma Concentration of ABI-H2158
timeFrame: Predose on Day 1, Week 4, Week 48, and Week 72
measure: Trough-to-Peak Plasma Concentration Ratio of ABI-H2158
timeFrame: 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
measure: Trough Plasma Concentration of ETV
timeFrame: Predose on Day 1, Week 4, Week 48, and Week 72
measure: Trough-to-Peak Plasma Concentration Ratio of ETV
timeFrame: 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
measure: Change in Mean log10 HBV pgRNA From Baseline to Week 24 and at Each Timepoint for ABI-H2158+ETV and PBO+ETV
timeFrame: up to Week 72
measure: Number of Participants With Reduction in HBV DNA Below the Assay Lower Limit of Quantitation
timeFrame: Up to 72 weeks
measure: Number of Participants With Reduction in HBV pgRNA Below the Assay Lower Limit of Quantitation
timeFrame: Up to 72 weeks
measure: Change From Baseline in Serum HBV Surface Antigen (HBsAg)
timeFrame: Baseline and up to 72 weeks
measure: Change From Baseline in Serum HBV "e" Antigen (HBeAg)
timeFrame: Baseline and up to 72 weeks
measure: Change From Baseline in Serum HBV Core-related Antigen (HBcrAg)
timeFrame: Baseline and up to 72 weeks
measure: 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
timeFrame: Baseline and up to Week 24
measure: Ncidence of HBV Variants With Reduced Susceptibility to ABI-H2158
timeFrame: Up to 72 weeks
measure: Change in Mean log10 HBV DNA for ABI-H2158+ETV and PBO+ETV at Each Timepoint
timeFrame: up to 72 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Coalition of Inclusive Medicine
state: California
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: Redwood City
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: Research and Education Inc.
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Miami
country: United States
facility: University of Miami/Schiff Center for Liver Diseases
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Flushing
country: United States
facility: New Discovery, LLC
state: New York
city: Manhasset
country: United States
facility: Northwell Health Center for Liver Disease
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: San Antonio
country: United States
facility: American Research Corporation at the Texas Liver Institute
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: New Lambton
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Greenslopes
country: Australia
facility: Gallipoli Medical Research Foundation
state: Queensland
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: Melbourne Health
state: Victoria
city: Vancouver
country: Canada
facility: (G.I.R.I.) GI Research Institute
state: British Columbia
city: Toronto
country: Canada
facility: Toronto Liver Centre
state: Ontario
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Chongqing
country: China
facility: The Second Affliated Hospital of Chongqing Medical University
state: Yuzhong District
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Guangzhou
country: China
facility: Nanfang Hospital
city: Guangzhou
country: China
facility: Guangzhou Eighth People's Hospital - Guangzhou Infectious Diseases Hospital
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital
state: New Territories
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Chuncheon
country: Korea, Republic of
facility: Hallym University Chuncheon Sacred Heart Hospital
state: Gangwon-do
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnam-do
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Hospital
state: Sanmin District
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei City
country: Taiwan
facility: Mackay Memorial Hospital Taipei Branch
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital (CGMH) - Linkou Branch
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
affiliation: Assembly Biosciences
name: Grace Wang
role: STUDY_DIRECTOR
References: