Intrahepatic and Peripheral Responses to Imdusiran (AB-729) in Chronic Hepatitis B

NCT06154278 | Recruiting Phase 2 FDA Drug

• 1 other identifier: HP-00106061
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn about the action of Imdusiran (AB-729) in the liver of people with chronic hepatitis B. The main questions it aims to answer are:

• how well is it working in the liver
• how does Imdusiran affect the hepatitis B virus Participants will receive injections of Imdusiran, one injection every 8 weeks, for a total of 4 doses. They will also undergo 2 liver biopsies: one with the first dose of Imdusiran, and the second 8 weeks after the last dose of Imdusiran.

Conditions

Chronic Hepatitis B

Keywords

hepatitis B; SiRNA; liver biopsy; Imdusiran

Outcome Measures

Primary Outcomes (1)

• Intrahepatic concentration of Imdusiran (AB-729)

  Intrahepatic drug concentration at day 0 (peak) and week 32 (trough)

  During intervention (with first dose of Imdusiran) and after intervention (8 weeks after last dose of Imdusiran)

Secondary Outcomes (8)

• Effect of Imdusiran (AB-729) on hepatitis B surface antigen production

  Baseline through study completion, an average of 1 year

• Effect of Imdusiran (AB-729) on hepatitis B surface antibody levels

  Baseline through study completion, an average of 1 year

• Effect of Imdusiran (AB-729) on hepatitis B virus RNA

  Baseline through study completion, an average of 1 year

• Effect of Imdusiran (AB-729) on hepatitis B virus e antigen production

  Baseline through study completion, an average of 1 year

• Effect of Imdusiran (AB-729) on hepatitis B surface antigen serostatus

  Baseline through study completion, an average of 1 year

Study Arms (1)

Imdusiran (AB-729)

EXPERIMENTAL

Participants receive subcutaneous injections of 60mg, one injection every 8 weeks for 4 doses.

Drug: Imdusiran (AB-729)

Interventions

Imdusiran (AB-729) DRUG

60mg subcutaneously, every 8 weeks, for a total of 4 doses

Imdusiran (AB-729)

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, over 18 years of age on the date of screening
• In good general health as evidenced by medical history
• Documented evidence of chronic hepatitis B infection (HBsAg positive at screening and for at least more than 6 months prior to screening)
• For females of reproductive potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline prior to study drug administration
• Male and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Have been on commercially available HBV oral antiviral treatment(s) for at least 6 months and willing to continue through the final study visit.
• HBV Deoxyribonucleic acid (DNA) ≤ 20 IU/mL for 6 or more months prior to Screening.
• Hepatitis B surface antigen titer ≥ 100 IU/mL.
• Liver imaging without liver mass suggestive of hepatocellular carcinoma within 12 months of day 0 AND Alpha fetoprotein \<10 ng/mL within 3 months of screening.

You may not qualify if:

• Known co-infection with any of the following:
• Human immunodeficiency virus (HIV)
• Hepatitis C virus (HCV), unless subjects are HCV Ab positive, but have a documented history of completing HCV treatment and/or negative HCV RNA
• Hepatitis D virus (HDV)
• Any known preexisting medical or psychiatric condition that could interfere with the subject's ability to provide informed consent or participate in study conduct, or that may confound study
• History of cirrhosis at any time, or evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding esophageal varices, hepatorenal syndrome, liver transplantation and/or hepatic encephalopathy.
• Liver ultrasound or other imaging with findings suggestive of hepatocellular carcinoma (HCC) at any time.
• Clinically unstable medical condition ≤2 weeks prior to the first dose of study treatment.
• Clinical diagnosis of substance abuse with alcohol, narcotics, or cocaine within the past 12 months except for those subjects monitored in an opioid substitution maintenance program.
• Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (e.g. basal cell skin cancer). Subjects under evaluation for possible malignancy are not eligible.
• Extensive bridging fibrosis or cirrhosis as defined clinically, by imaging or by the following:
• a. Metavir ≥ 3 or Ishak fibrosis score ≥ 4 by a liver biopsy within 3 years of screening, or, in the absence of an appropriate liver biopsy, either: i. Screening FibroTest score \>0.48 and APRI \>1, or ii. FibroScan with a result \>9 kPa within 12 months of screening
• If liver biopsy is available, the liver biopsy result supersedes (i) and (ii).
• Subjects meeting any of the following laboratory parameters at screening:
• Alanine aminotransferase (ALT) \>3x Upper Limit of Normal (ULN)

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Arbutus Biopharma Corporation: collaborator

Study Sites (1)

Institute of Human Virology, University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

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

Central Study Contacts

Lydia SY Tang, MBChB

CONTACT

+1(410)-706-6567; lydiatang@ihv.umaryland.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Single-center, non-randomized, pilot study of Imdusiran (AB-729) in virally suppressed adults with chronic hepatitis B on oral antiviral therapy.

Study Record Dates

• First Submitted: October 31, 2023
• First Posted: December 4, 2023
• Study Start: July 25, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)