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

Sponsor

University of Maryland, Baltimore (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06154278

Collaborator

Arbutus Biopharma Corporation (Industry)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: Imdusiran (AB-729)	Phase 2

Detailed Description

This is a single-center, non-randomized, pilot study of Imdusiran in adults with chronic hepatitis B on oral antiviral therapy. The primary objective of this study is to evaluate the intrahepatic concentrations of Imdusiran. The secondary objective is to evaluate the effect of Imdusiran on viral markers.

Up to 10 participants will receive a total of 4 subcutaneous injections of 60mg Imdusiran (one injection every 8 weeks). They will undergo 2 liver biopsies: one with the first dose, and the second 8 weeks after the last dose. There is an optional third liver biopsy at the end of study (week 52).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

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

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Pilot Study to Evaluate Intrahepatic and Peripheral Responses to Small Interfering RNA, Imdusiran (AB-729), Among People With Chronic Hepatitis B

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Imdusiran (AB-729) Participants receive subcutaneous injections of 60mg, one injection every 8 weeks for 4 doses.	Drug: Imdusiran (AB-729) 60mg subcutaneously, every 8 weeks, for a total of 4 doses

Arm

Intervention/Treatment

Experimental: Imdusiran (AB-729)

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

Drug: Imdusiran (AB-729)

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

Outcome Measures

Primary Outcome Measures

Intrahepatic concentration of Imdusiran (AB-729) [During intervention (with first dose of Imdusiran) and after intervention (8 weeks after last dose of Imdusiran)]
Intrahepatic drug concentration at day 0 (peak) and week 32 (trough)

Secondary Outcome Measures

Effect of Imdusiran (AB-729) on hepatitis B surface antigen production [Baseline through study completion, an average of 1 year]
Change in hepatitis B surface antigen titer with Imdusiran
Effect of Imdusiran (AB-729) on hepatitis B surface antibody levels [Baseline through study completion, an average of 1 year]
Change in hepatitis B surface antigen-specific antibody levels (anti-HBsAg)
Effect of Imdusiran (AB-729) on hepatitis B virus RNA [Baseline through study completion, an average of 1 year]
Change in HBV RNA production
Effect of Imdusiran (AB-729) on hepatitis B virus e antigen production [Baseline through study completion, an average of 1 year]
Change in quantitative HBeAg
Effect of Imdusiran (AB-729) on hepatitis B surface antigen serostatus [Baseline through study completion, an average of 1 year]
Proportion of participants with hepatitis B surface antigen loss
Effect of Imdusiran (AB-729) on hepatitis B surface antibody serostatus [Baseline through study completion, an average of 1 year]
Proportion of participants with anti-HBsAg seroconversion
Effect of Imdusiran (AB-729) on hepatitis B e antigen serostatus [Baseline through study completion, an average of 1 year]
Proportion of participants with HBeAg loss
Effect of Imdusiran (AB-729) on hepatitis B e antibody serostatus [Baseline through study completion, an average of 1 year]
Proportion of participants with anti-HBeAg seroconversion

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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:

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)
Direct bilirubin (if total bilirubin elevated) >1.5 × ULN of the laboratory reference range.
Prothrombin (PT) or Activated Partial Thromboplastin Clotting Time (APTT) over the upper limit of normal.
Platelet count <100,000/microliters
Estimated glomerular filtration rate, calculated by the chronic kidney disease epidemiology collaboration formula: <60 mL/min/1.73 m2
Significant cardiovascular, pulmonary, or neurological disease in the opinion of the investigator.
Participation in any investigational drug, vaccine, or device study within 30 days before study treatment administration, or 90 days for a biologic study, or at any time during participation in the study.
Pregnancy or lactation
Believed by the Study Investigator to be inappropriate for study participation for any reason not otherwise listed