A Study Evaluating ABI-H0731 as Adjunctive Therapy in Participants With Chronic Hepatitis B Infection

A Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731 as Adjunctive Therapy in Virally-suppressed Patients With Chronic Hepatitis B

The purpose of this study is to determine if ABI-H0731 given in combination with a standard of care (SOC) hepatitis B virus (HBV) nucleos(t)ide reverse transcriptase inhibitor (NUC) medication is safe and effective in participants with chronic hepatitis B virus infection (cHBV).

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: ABI-H0731; Drug: SOC NUC; Drug: Placebo Oral Tablet

Detailed Description

This is a Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731 as Adjunctive Therapy in Virally-suppressed Participants with cHBV.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Toronto, Canada
    • Toronto General Hospital
  • Toronto, Canada
    • Toronto Liver Center
  • Vancouver, Canada
    • GI Research Institute
• New Zealand
  • Auckland, New Zealand
    • Auckland City Hospital
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Cedars-Sinai Medical Center
    • Coronado, California, United States, 92118
      • Southern California Research Center
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Los Angeles, California, United States, 90057
      • Asia Pacific Liver Center
    • San Diego, California, United States, 92105
      • Research and Education
    • San Diego, California, United States, 92123
      • Medical Associates Research Group
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
    • Catonsville, Maryland, United States, 21228
      • Digestive Disease Associates
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • Infectious Disease Care
  • New York
    • Flushing, New York, United States, 11354
      • Sing Chan, MD
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10016
      • NYU Langone Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Xiaoli Ma, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Male or female between ages 18 and 70 years
• Virologically-suppressed (defined as HBV DNA ≤limit of quantitation (LOQ) for at least 6 months before screening on SOC NUC therapy
• HBeAg-positive or HBeAg-negative at screening
• In good general health except for cHBV

Key Exclusion Criteria:

• Co-infection with HIV, hepatitis C virus (HCV), hepatitis E virus (HEV) or hepatitis D virus (HDV)
• History or evidence of hepatic decompensation (including gastrointestinal bleeding or esophageal varices) at any time prior to or at time of screening
• Clinically significant cardiac or pulmonary disease, chronic or recurrent renal or urinary tract disease, liver disease other than HBV, endocrine disorder, autoimmune disorder, diabetes mellitus requiring treatment with insulin or hypoglycemic agents, neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment, 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 participant unsuitable for the study
• Previous treatment with an investigational agent for HBV other than ABI-H0731 in the last 6 months before screening
• History of hepatocellular carcinoma (HCC)
• Females who are lactating or pregnant or wish to become pregnant are excluded from the study

• Exclusionary laboratory parameters at screening include:

  • Platelet count <100,000/mm3
  • Albumin <lower limit of normal (LLN)
  • Direct bilirubin >1.2×upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) >5×ULN at screening
  • International Normalized Ratio (INR) >1.5×ULN
  • Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ABI-H0731 + SOC NUC; Virologically suppressed participants will receive ABI-H0731 along with SOC NUC (ETV, TDF or TAF) tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary.	Drug: ABI-H0731; Participants will receive ABI-H0731 300 mg tablets orally once daily (QD).; Drug: SOC NUC; Participants will continue on their SOC NUC (ETV, TDF or TAF) tablet orally as per approved package insert.; Other Names: Tenofovir disoproxil fumarate (TDF); Entecavir (ETV); Tenofovir alafenamide (TAF)
ACTIVE_COMPARATOR: Placebo + SOC NUC; Virologically suppressed participants will receive matching placebo tablets and continue their SOC NUC (ETV, TDF or TAF) for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary.	Drug: SOC NUC; Participants will continue on their SOC NUC (ETV, TDF or TAF) tablet orally as per approved package insert.; Other Names: Tenofovir disoproxil fumarate (TDF); Entecavir (ETV); Tenofovir alafenamide (TAF); Drug: Placebo Oral Tablet; Participants will receive placebo matching ABI-0731 tablets orally QD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Mean log10 Serum HBsAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC	Baseline to Week 24
Change in Mean log10 Serum HBeAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Premature Study Discontinuation		Up to Follow-up (maximum up to Week 36)
Number of Participants With One or More Abnormal Safety Laboratory Result		Up to Week 36
Number of Participants With a Clinically-significant Electrocardiogram Abnormality		Up to Week 24
Number of Participants With a Clinically-significant Change in Vital Signs	Vital signs assessed were body temperature, respiratory rate, and pulse rate	Baseline and up to Week 24
Number of Participants With One or More Adverse Events		Up to Follow-up (maximum up to Week 36)
Number of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at Week 24 on ABI-H0731 + NUC Therapy as Compared With Placebo + NUC Therapy	Abnormal ALT was defined as ≥1.25 x upper limit of normal (34 Units/L for female and 43 Units/L for male participants).	Baseline to Week 24
Trough Levels of ABI-H0731 on ABI-H0731 + SOC NUC Therapy		Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Trough Levels of Entecavir (ETV) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy		Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Trough Levels of Tenofovir Alafenamide (TAF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy		Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Trough Levels of Tenofovir Disoproxil Fumarate (TDF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy		Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + SOC NUC Therapy		Baseline, Weeks 2, 4, 12, and 24
Trough to Peak Ratios of SOC NUC on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy		Baseline, Weeks 2, 4, 12, and 24

Collaborators and Investigators

• Sponsor: Assembly Biosciences

Publications and helpful links

General Publications

• Yuen MF, Agarwal K, Ma X, Nguyen TT, Schiff ER, Hann HL, Dieterich DT, Nahass RG, Park JS, Chan S, Han SB, Gane EJ, Bennett M, Alves K, Evanchik M, Yan R, Huang Q, Lopatin U, Colonno R, Ma J, Knox SJ, Stamm LM, Bonacini M, Jacobson IM, Ayoub WS, Weilert F, Ravendhran N, Ramji A, Kwo PY, Elkhashab M, Hassanein T, Bae HS, Lalezari JP, Fung SK, Sulkowski MS. Safety and efficacy of vebicorvir in virologically suppressed patients with chronic hepatitis B virus infection. J Hepatol. 2022 Sep;77(3):642-652. doi: 10.1016/j.jhep.2022.04.005. Epub 2022 Apr 20.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 11, 2018
• Primary Completion (ACTUAL): July 5, 2019
• Study Completion (ACTUAL): July 5, 2019

Study Registration Dates

• First Submitted: June 6, 2018
• First Submitted That Met QC Criteria: July 2, 2018
• First Posted (ACTUAL): July 3, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 17, 2021
• Last Update Submitted That Met QC Criteria: January 29, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: HBV; HBeAg-positive; hepatitis B; vebicorvir; VBR; Chronic hepatitis B; HBeAg-negative
• 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; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Entecavir
• Other Study ID Numbers: ABI-H0731-201

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