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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Imdusiran (AB-729) for chronic hepatitis B?

The research mentions that similar drugs like lamivudine and adefovir dipivoxil have been effective in treating chronic hepatitis B, with lamivudine showing promise despite some resistance issues, and adefovir dipivoxil having a low resistance rate. This suggests that drugs targeting hepatitis B, like Imdusiran, may also be effective. ^{1 2 3 4 5}

Eligibility Criteria

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

I am over 18 years old.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Lamivudine as initial treatment for chronic hepatitis B in the United States. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Drug insight: Nucleoside and nucleotide analog inhibitors for hepatitis B. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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

5. China 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]. [2013]