A Study Evaluating Treatment Intensification With ABI-H0731 in Participants With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors

NCT ID: NCT04454567

Last Updated: 2022-10-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-11
• Study Completion Date: 2021-04-08

Brief Summary

This study will explore the safety and antiviral activity of ABI-H0731 when added to a nucleos(t)ide reverse transcriptase inhibitor (NrtI) in participants who are partially virologically suppressed.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

ABI-H0731 + SOC NrtI

Participants with chronic hepatitis B virus (HBV) infection with partial virologic suppression on NrtI alone will receive ABI-H0731 300 mg once daily plus standard of care (SOC) NrtI for 96 weeks, followed by SOC NrtI alone for an additional 24 weeks (120 weeks total).

Group Type: EXPERIMENTAL

ABI-H0731

Intervention Type: DRUG

Participants will receive ABI-H0731 tablets orally once daily

NrtI

Intervention Type: DRUG

Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert

Placebo + SOC NrtI

Participants with chronic HBV infection with partial virologic suppression on NrtI alone will receive placebo to ABI-H0731 once daily plus SOC NrtI for 48 weeks, followed by ABI-H0731 300 mg once daily plus SOC NrtI for Weeks 48 to 96, followed by SOC NrtI alone for Weeks 96 to 120.

Group Type: PLACEBO_COMPARATOR

ABI-H0731

Intervention Type: DRUG

Participants will receive ABI-H0731 tablets orally once daily

Placebo

Intervention Type: DRUG

Participants will receive placebo to ABI-H0731 tablets orally once daily

NrtI

Intervention Type: DRUG

Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert

Interventions

ABI-H0731

Participants will receive ABI-H0731 tablets orally once daily

Intervention Type: DRUG

Placebo

Participants will receive placebo to ABI-H0731 tablets orally once daily

Intervention Type: DRUG

NrtI

Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert

Intervention Type: DRUG

Other Intervention Names

Nucleos(t)ide reverse transcriptase inhibitor

Eligibility Criteria

Inclusion Criteria

• Body mass index (BMI) 18 to 36 kg/m^2 and a minimum body weight of 45 kg (inclusive)
• In good general health except for chronic hepatitis B (CHB)
• HBeAg positive or HBeAg negative chronic hepatitis B
• HBV DNA >LLOQ using a commercially available assay with LLOQ=20 IU/mL
• On a stable NrtI regimen (ETV, TDF or TAF) for more than 12 months
• Lack of cirrhosis or advanced liver disease

Exclusion Criteria

• Current or prior treatment for CHB with lamivudine, telbivudine, adefovir, HBV core inhibitor, or previous treatment with an investigational agent for HBV infection
• Presence of substitutions in the HBV polymerase coding region which may confer reduced susceptibility to NrtIs
• Co-infection with human immunodeficiency virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, or hepatitis D virus
• Females who are lactating or wish to become pregnant during the course of the trial
• History or evidence of advanced liver disease or hepatic decompensation
• Clinically significant cardiac disease including poorly-controlled or unstable hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease; liver disease other than CHB; endocrine disorder; autoimmune disorder; poorly controlled diabetes mellitus; neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment; ongoing infection or other medical conditions requiring frequent medical management or pharmacologic or surgical treatment that, in the opinion of the Investigator or the Sponsor, makes the subject unsuitable for trial participation
• History of hepatocellular carcinoma (HCC)
• Exclusionary laboratory parameters at Screening:

• Platelet count <100,000/mm^3
• Albumin <lower limit of normal
• Total bilirubin >1.2 × upper limit of normal (ULN)
• Direct bilirubin >1.2 × ULN
• ALT >10 × ULN
• Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is >ULN but <100 ng/mL, the participant is eligible if a hepatic imaging trial prior to initiation of study drug reveals no lesions indicative of possible HCC.
• International Normalized Ratio >1.5 × ULN
• Glomerular filtration rate <50 mL/min/1.73 m^2 by Chronic Kidney Disease Epidemiology Collaboration equation
• Any other laboratory abnormality deemed clinically significant by the Sponsor or the Investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assembly Biosciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Knox

Role: STUDY_DIRECTOR

Assembly Biosciences

Locations

Asia Pacific Liver Center

Los Angeles, California, United States

California Liver Research Institute

Pasadena, California, United States

Research and Education

San Diego, California, United States

Quest Clinical Research

San Francisco, California, United States

Schiff Center for Liver Disease

Miami, Florida, United States

Institute of Human Virology

Baltimore, Maryland, United States

Infectious Disease Care

Hillsborough, New Jersey, United States

Northwell Health

Manhasset, New York, United States

Office of X.M., MD

Philadelphia, Pennsylvania, United States

Prince of Wales Hospital

Hong Kong, , Hong Kong

Queen Mary Hospital

Hong Kong, , Hong Kong

Auckland Clinical Studies

Grafton, Auckland, New Zealand

Countries

United States; Hong Kong; New Zealand

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UTN 1111-1251-7136

Identifier Type: OTHER

Identifier Source: secondary_id

ABI-H0731-205

Identifier Type: -

Identifier Source: org_study_id