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

NCT04398134 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: ABI-H2158-2012019-004902-85
• Study Type: interventional
• Target: 88
• Locations: 9 countries
• Sites: 44

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.

Conditions

Chronic Hepatitis B

Keywords

HBV; hepatitis B

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (13)

• 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

Study Arms (2)

ABI-H2158 plus ETV

EXPERIMENTAL

ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks

Drug: ABI-H2158; Drug: Entecavir (ETV)

Placebo plus ETV

PLACEBO COMPARATOR

Placebo matching ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks

Drug: Placebo; Drug: Entecavir (ETV)

Interventions

ABI-H2158 DRUG

3 X 100 mg tablets for oral administration

ABI-H2158 plus ETV

Placebo DRUG

Sugar pill manufactured to mimic the ABI-H2158 tablets

Placebo plus ETV

Entecavir (ETV) DRUG

0.5 mg tablet for oral administration

ABI-H2158 plus ETV; Placebo plus ETV

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assembly Biosciences: lead

Study Sites (44)

Coalition of Inclusive Medicine

Los Angeles, California, 90020, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Stanford University Medical Center

Redwood City, California, 94063, United States

Location

Research and Education Inc.

San Diego, California, 92105, United States

Location

Quest Clinical Research

San Francisco, California, 94115, United States

Location

University of Miami/Schiff Center for Liver Diseases

Miami, Florida, 33136, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

New Discovery, LLC

Flushing, New York, 11355, United States

Location

Northwell Health Center for Liver Disease

Manhasset, New York, 11030, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

American Research Corporation at the Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

St. Vincent's Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

John Hunter Hospital

New Lambton, New South Wales, 2305, Australia

Location

Gallipoli Medical Research Foundation

Greenslopes, Queensland, 4120, Australia

Location

St. Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Melbourne Health

Parkville, Victoria, 3050, Australia

Location

(G.I.R.I.) GI Research Institute

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Toronto Liver Centre

Toronto, Ontario, M6H 3M1, Canada

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

The Second Affliated Hospital of Chongqing Medical University

Chongqing, Yuzhong District, 400010, China

Location

Xiangya Hospital Central South University

Changsha, 410008, China

Location

Nanfang Hospital

Guangzhou, 510515, China

Location

Guangzhou Eighth People's Hospital - Guangzhou Infectious Diseases Hospital

Guangzhou, China

Location

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Auckland Clinical Studies

Auckland, 2105, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, Gangwon-do, 24253, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan, Gyeongsangnam-do, 50612, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

SMG-SNU Boramae Medical Center

Seoul, 07061, South Korea

Location

Kaohsiung Medical University Hospital

Kaohsiung City, Sanmin District, 80756, Taiwan

Location

China Medical University Hospital

Taichung, 44047, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Mackay Memorial Hospital Taipei Branch

Taipei, 10449, Taiwan

Location

Chang Gung Memorial Hospital (CGMH) - Linkou Branch

Taoyuan District, 333, Taiwan

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

entecavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Study ABI-H2158-201 was terminated early due to alanine aminotransferase (ALT) elevations among study participants who received ABI-H2158 (and not among those who received PBO). Further details on these events are described in the results section below. In the absence of an alternative etiology for the ALT elevations, further clinical development of ABI-H2158 was terminated by the Sponsor.

Results Point of Contact

• Title: Executive Director of Clinical Operations
• Organization: Assembly Biosciences

Clinicaltrials@assemblybio.com

833-509-4583

Study Officials

• Grace Wang

  Assembly Biosciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2020
• First Posted: May 21, 2020
• Study Start: August 28, 2020
• Primary Completion: October 14, 2021
• Study Completion: December 28, 2021
• Last Updated: September 15, 2022
• Results First Posted: August 26, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (13); NZ (2); CN (5); KR (7); TW (5); CA (2); AU (7); HK (2); GB (1)