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

A Phase 2a, Multi-Center, Single-Blind, Placebo-Controlled Study Evaluating Treatment Intensification With ABI-H0731 in Subjects With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: ABI-H0731; Drug: NrtI; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Auckland Clinical Studies
• United States
  • California
    • Los Angeles, California, United States, 90057
      • Asia Pacific Liver Center
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • San Diego, California, United States, 92115
      • Research and Education
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
  • Florida
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Disease
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Institute of Human Virology
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • Infectious Disease Care
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Office of X.M., MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: ABI-H0731; Participants will receive ABI-H0731 tablets orally once daily; Drug: NrtI; Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert; Other Names: Nucleos(t)ide reverse transcriptase inhibitor
Placebo Comparator: 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.	Drug: ABI-H0731; Participants will receive ABI-H0731 tablets orally once daily; Drug: NrtI; Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert; Other Names: Nucleos(t)ide reverse transcriptase inhibitor; Drug: Placebo; Participants will receive placebo to ABI-H0731 tablets orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With an Adverse Event	Baseline and up to 5 months
Number of Participants With Premature Discontinuation of Treatment	Baseline and up to 5 months
Number of Participants With a Laboratory Abnormality	Baseline and up to 5 months
Number of Participants With HBV DNA <Lower Limit of Quantification (LLOQ) at Week 48	Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean Change From Baseline in log10 HBV DNA	Baseline and up to 5 months
Number of Participants With HBV DNA <LLOQ at Each Timepoint	Baseline and up to 5 months
Number of Participants With HBV DNA <Limit of Detection (LOD)	Baseline and up to 5 months
Mean Change From Baseline in log10 HBV Pregenomic RNA (pgRNA)	Baseline and up to 5 months
Number of Participants With HBV pgRNA <LLOQ	Baseline and up to 5 months
Mean Change From Baseline in log10 Serum Hepatitis B 'e' Antigen (HBeAg)	Baseline and up to 5 months
Mean Change From Baseline in log10 Serum Hepatitis B Core-related Antigen (HBcrAg)	Baseline and up to 5 months
Mean Change From Baseline in log10 Serum Hepatitis B Surface Antigen (HBsAg)	Baseline and up to 5 months
Number of Participants With Normalized Alanine Aminotransferase (ALT)	Baseline and up to 5 months
Plasma Concentrations of ABI-H0731	Baseline and up to 5 months
Plasma Concentrations of Entecavir	Baseline and up to 5 months
Incidence of HBV Variants Among Participants With Evidence of Non-response to Treatment	Baseline and up to 5 months

Collaborators and Investigators

• Sponsor: Assembly Biosciences
• Investigators: Study Director: Steven Knox, Assembly Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2020
• Primary Completion (Actual): April 8, 2021
• Study Completion (Actual): April 8, 2021

Study Registration Dates

• First Submitted: June 18, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): October 20, 2022
• Last Update Submitted That Met QC Criteria: September 23, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Reverse Transcriptase Inhibitors
• Other Study ID Numbers: ABI-H0731-205; UTN 1111-1251-7136 (Other Identifier: World Health Organization)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No