Imdusiran for Chronic Hepatitis B

(i-LIVER Trial)

Overseen By Lydia SY Tang, MBChB

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Must be taking: HBV oral antivirals

Disqualifiers: HIV, HCV, Cirrhosis, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 32 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called Imdusiran (also known as AB-729) to evaluate its effects in the liver of people with chronic hepatitis B. Researchers aim to determine if Imdusiran can effectively target the hepatitis B virus. Participants will receive injections of Imdusiran every 8 weeks and undergo two liver biopsies to assess its effects. Those who have had hepatitis B for at least 6 months and are already on antiviral medication might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you continue taking your current hepatitis B oral antiviral medications throughout the study.

Is there any evidence suggesting that Imdusiran (AB-729) is likely to be safe for humans?

Research shows that Imdusiran (AB-729) is generally safe and well-tolerated. Previous studies found that participants experienced few serious side effects. These studies tested both single and multiple doses, and the treatment still showed good safety results. Most participants did not have severe negative reactions. However, like any treatment, some mild side effects might occur. The studies also found that Imdusiran effectively reduced the hepatitis B virus, offering promise for those with chronic hepatitis B. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hepatitis B?

Unlike the standard treatments for chronic Hepatitis B, which often include antiviral medications like entecavir and tenofovir, Imdusiran (AB-729) offers a new approach. This treatment works by targeting the virus's RNA, potentially reducing the virus's ability to replicate and cause liver damage. Researchers are excited about Imdusiran because it is administered via subcutaneous injections every eight weeks, which could offer a more convenient dosing schedule compared to daily oral medications. Additionally, its unique mechanism of action might provide a new avenue to reduce viral load and improve patient outcomes.

What evidence suggests that Imdusiran might be an effective treatment for chronic hepatitis B?

Research shows that Imdusiran (AB-729), the treatment under study in this trial, holds promise for treating chronic hepatitis B. Studies have found that up to 50% of patients using Imdusiran achieved a functional cure, meaning the virus became inactive in their bodies. Imdusiran targets and reduces a protein produced by the virus, helping to control the virus and boost the immune system. This treatment effectively lowers the virus's activity and the substances that trigger an immune response. Current evidence suggests that Imdusiran could be a strong option in the fight against chronic hepatitis B. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic hepatitis B who've been on HBV oral antiviral treatments for at least 6 months and have a certain level of hepatitis B surface antigen. They must be in good health, not pregnant, willing to continue their current treatment, and use contraception if applicable.

Inclusion Criteria

I have been on HBV medication for 6 months and can continue it.

You need to sign and date a form that says you agree to take part in the study.

You have high levels of hepatitis B surface antigen in your blood.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous injections of Imdusiran (AB-729), one injection every 8 weeks for a total of 4 doses, with liver biopsies conducted at the first dose and 8 weeks after the last dose

32 weeks

4 visits (in-person) for injections, 2 visits (in-person) for liver biopsies

Follow-up

Participants are monitored for safety and effectiveness after treatment, with an optional third liver biopsy at the end of the study

20 weeks

1 optional visit (in-person) for liver biopsy

What Are the Treatments Tested in This Trial?

Interventions

• Imdusiran (AB-729)

Trial Overview

The trial studies Imdusiran (AB-729) effects on the liver and hepatitis B virus. Participants will get one injection every 8 weeks for a total of four doses and undergo two liver biopsies—one at the start and another after the final dose.

How Is the Trial Designed?

Group I: Imdusiran (AB-729) Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Arbutus Biopharma Corporation

Industry Sponsor

Trials

13

Recruited

660+

Published Research Related to This Trial

Pradefovir, an oral prodrug of adefovir designed to target the liver, is being developed by Metabasis Therapeutics for treating HBV infection.

Phase II clinical trials for pradefovir have been completed, indicating progress in its development as a potential treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pradefovir, a liver-targeted prodrug of adefovir against HBV infection. Tillmann, HL.[2013]

Adefovir dipivoxil (ADV) significantly reduced HBV DNA levels in chronic hepatitis B patients with lamivudine resistance, showing a greater reduction compared to lamivudine after 24 and 48 weeks of treatment.

The treatment with ADV was found to be safe, with no severe adverse events related to the drug, indicating it is a viable option for patients who have developed resistance to lamivudine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A double-blind, randomized, lamivudine-controlled clinical trial of DAIDING (adefovir dipivoxil) for lamivudine-resistant patients with chronic hepatitis B]. Wang, YM., Chen, YK., Zhang, DZ., et al.[2013]

In a study of 143 patients with chronic hepatitis B, those treated with lamivudine for 52 weeks showed significantly better outcomes compared to placebo, including a 52% histologic response and a 44% rate of sustained suppression of HBV DNA to undetectable levels.

Lamivudine was well tolerated, with most patients maintaining positive treatment responses for 16 weeks after stopping the medication, although some experienced temporary increases in liver enzyme levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lamivudine as initial treatment for chronic hepatitis B in the United States. Dienstag, JL., Schiff, ER., Wright, TL., et al.[2013]

Lamivudine and adefovir dipivoxil are both effective antiviral treatments for chronic hepatitis B, showing similar efficacy in reducing the virus.

Lamivudine has minimal side effects but a high risk of drug resistance, while adefovir dipivoxil has a lower resistance rate but carries a small risk of kidney toxicity with long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug insight: Nucleoside and nucleotide analog inhibitors for hepatitis B. Fung, SK., Lok, AS.[2022]

Entecavir is a potent new treatment for chronic hepatitis B virus (HBV) infection, showing superior efficacy compared to lamivudine in clinical trials involving nucleoside-naïve and lamivudine-resistant patients.

It has a unique three-step mechanism of action, minimal major adverse effects, and a low potential for developing resistance, making it a promising first- or second-line therapy for HBV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of entecavir in the treatment of chronic hepatitis B infection. Rivkin, A.[2014]

Citations

1.

investor.arbutusbio.com

investor.arbutusbio.com/news-releases/news-release-details/arbutus-presents-clinical-trial-data-its-two-hbv-assets

Arbutus Presents Clinical Trial Data from its Two HBV Assets ...

Data highlighted in late-breaker poster presentation shows that imdusiran achieves functional cure in chronic hepatitis B (cHBV) patients ...

2.

clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT06277037?draw=2&rank=1

Long-Term Follow-up Study for Subjects With CHB ...

It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

3.

contagionlive.com

contagionlive.com/view/imdusiran-for-chronic-hepatitis-b-achieves-functional-cure-in-50-of-patients

Imdusiran for Chronic Hepatitis B Achieves Functional ...

The data, showing up to 50% of patients achieving a functional cure, will be presented at The Liver Meeting® 2024, hosted by the American ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39306863/

Control of Hepatitis B Virus with Imdusiran, a Small ...

Imdusiran (AB-729), a novel, pan-genotypic siRNA therapeutic that effectively reduces HBsAg, viral antigens, and viral replication in chronic hepatitis B ...

5.

investor.arbutusbio.com

investor.arbutusbio.com/node/18911/pdf

Arbutus' Imdusiran Achieves Functional Cure in cHBV Patients ...

Additional immune activation data in those patients in Cohort A1 that achieved a functional cure will be presented by Dr. Emily Thi, Senior ...

6.

investors.barinthusbio.com

investors.barinthusbio.com/news-releases/news-release-details/arbutus-and-barinthus-bio-announce-new-data-im-prove-ii-trial

Arbutus and Barinthus Bio Announce New Data from the IM ...

Clinical data generated thus far has shown single and multiple doses of imdusiran to be generally safe and well-tolerated, while also providing ...

7.

natap.org

natap.org/2018/EASL/EASL_82.htm

Durable inhibition of hepatitis B virusreplication and ...

ARB-270729 is a promising new agent to potentiate HBV cure and acts on multiple hepatitis B viral transcripts, enabling inhibition of HBV replication and ...