Open-Label Study of AB-729, Nucleos(t)Ide Analogue and Pegylated Interferon Alfa-2a in Subjects With Chronic Hepatitis B Infection

A Randomized, Open-Label, Multicenter Study Investigating AB-729, Nucleos(t)Ide Analogue and Pegylated Interferon Alfa-2a Treatment in Subjects With Chronic Hepatitis B Infection

This is a randomized, open label, multicenter Phase 2 study investigating the safety and antiviral activity of AB-729 in combination with ongoing NA therapy and short courses of Peg-IFNα-2a in subjects with CHB.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis b
• Intervention / Treatment: Drug: AB-729; Drug: Peg-IFNα-2a

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital, The Chinese University of Hong Kong
• Moldova
  • Chisinau, Moldova, 2025
    • Arensia Exploratory Medicine Moldova
• South Korea
  • Seoul, South Korea
    • Asan Medical Center
  • Republic of Korea
    • Pusan, Republic of Korea, South Korea, 49241
      • Pusan National University Hospital
• Taiwan
  • Chiayi City, Taiwan, 60002
    • Chia-Yi Christian Hospital
  • Kaohsiung City, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital
  • Kaohsiung City, Taiwan, 83301
    • Chung-Ho Memorial Hospital
• Ukraine
  • Kyiv, Ukraine, 01135
    • Medical Center of Limited Liability Company Harmoniya Krasy
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Liver Health
    • Tucson, Arizona, United States, 85712
      • Arizona Liver Health
  • California
    • San Diego, California, United States, 92105
      • Research and Education, Inc.
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • ID Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Chronic hepatitis B virus infection with documentation at least 6 months prior to screening
• Subjects must have been receiving either TAF, TDF (or equivalent), or ETV consistently for ≥12 months prior to dosing Day 1
• HBV DNA <LLOQ at Screening
• HBsAg between 100 and 5,000 IU/mL at Screening
• Subjects must be HBeAg-negative at Screening
• Fibroscan® result of ≤8.5 kPa within 6 months prior to dosing Day 1
• Medically stable based on physical examination, medical history, vital signs, laboratory values, and 12-lead Electrocardiogram (ECG) at screening

Exclusion Criteria:

• Evidence of co-infection with hepatitis A, C, D or E virus or human immunodeficiency virus (HIV) at screening
• History of any clinically significant medical condition associated with chronic liver disease, cirrhosis, evidence of decompensated liver disease, or findings suggestive of hepatocellular carcinoma (HCC) at any time
• Contraindications to the use of Peg-IFNα-2a or incapable of self-administration or assisted administration of Peg-IFNα-2a
• Previous treatment with an experimental HBV-directed RNA-interference or antisense oligonucleotide product.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A, Group 1; AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks.	Drug: AB-729; subcutaneous injection; Drug: Peg-IFNα-2a; subcutaneous injection; Other Names: pegylated interferon alpha 2a
Experimental: Cohort A, Group 2; AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks.	Drug: AB-729; subcutaneous injection; Drug: Peg-IFNα-2a; subcutaneous injection; Other Names: pegylated interferon alpha 2a
Experimental: Cohort B, Group 1; AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks.	Drug: AB-729; subcutaneous injection; Drug: Peg-IFNα-2a; subcutaneous injection; Other Names: pegylated interferon alpha 2a
Experimental: Cohort B, Group 2; AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks.	Drug: AB-729; subcutaneous injection; Drug: Peg-IFNα-2a; subcutaneous injection; Other Names: pegylated interferon alpha 2a

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Frequency and Severity of Treatment Emergent Adverse Events (TEAEs), Discontinuations Due to AEs and Lab Abnormalities After Dosing With AB-729 Plus Peg-IFNα-2a	Up to 124 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in HBsAg and Other Virologic Markers at Each Time Point	Up to 124 weeks
Proportion of Subjects With HBsAb Seroconversion at Each Timepoint	Up to 124 weeks
Proportion of Subjects Who Are Eligible to Stop NA After Week 24 of Follow up	Up to 76 weeks
Proportion of Subjects Who Discontinue NA and Subsequently Restart NA Therapy After Meeting Criteria	Up to 124 weeks
Proportion of Subjects Who Discontinue NA and Subsequently Meet Protocol Defined Clinical Relapse Criteria. Proportion of Subjects Who Discontinue NA and Subsequently Meet Protocol Defined Viral Relapse Criteria	Up to 124 weeks
Post-dose Plasma Concentrations of AB-729 Anti-sense (AS), AB-729 AS(N-1)3', and AB-729 AS(N-2)3' at Selected Timepoints	Up to 40 weeks

Collaborators and Investigators

• Sponsor: Arbutus Biopharma Corporation

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2021
• Primary Completion (Actual): March 13, 2025
• Study Completion (Actual): May 21, 2025

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: July 19, 2021
• First Posted (Actual): July 28, 2021

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Hepatitis; HBV; CHB; Chronic hepatitis B; Hepatitis B virus
• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Pathological Conditions, Signs and Symptoms; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Anti-Infective Agents; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antiviral Agents; Interferon alpha-2; Peginterferon alfa-2a; Interferons; Interferon-alpha
• Other Study ID Numbers: AB-729-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No