Imdusiran for Chronic Hepatitis B

(i-LIVER Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Maryland, Baltimore

Must be taking: HBV oral antivirals

Disqualifiers: HIV, HCV, Cirrhosis, Malignancy, others

No Placebo Group

Prior Safety Data

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.

Trial 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) (Antisense Oligonucleotide)

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Institute of Human Virology, University of Maryland School of Medicine Baltimore, MD

Who Is Running the Clinical Trial?

University of Maryland, Baltimore Lead Sponsor

Arbutus Biopharma Corporation Industry Sponsor

References

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

Pradefovir, a liver-targeted prodrug of adefovir against HBV infection. [2013] Metabasis Therapeutics Inc (previously Ribapharm Inc) is developing pradefovir, an oral liver-targeting prodrug of adefovir developed using its HepDirect technology, for the potential treatment of HBV infection. Phase II clinical trials of pradefovir have been completed.

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

Lamivudine as initial treatment for chronic hepatitis B in the United States. [2013] Although the nucleoside analogue lamivudine has shown promise in patients with chronic hepatitis B, long-term data on patients from the United States are lacking. We randomly assigned previously untreated patients with chronic hepatitis B to receive either 100 mg of oral lamivudine or placebo daily for 52 weeks. We then followed them for an additional 16 weeks to evaluate post-treatment safety and the durability of responses. The primary end point with respect to efficacy was a reduction of at least 2 points in the score on the Histologic Activity Index. On this scale, scores can range from 0 (normal) to 22 (most severe abnormalities).

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

Drug insight: Nucleoside and nucleotide analog inhibitors for hepatitis B. [2022] In the past decade, substantial advances have been made in the treatment of chronic hepatitis B. Approved treatments include interferon-alpha, the nucleoside analog inhibitor lamivudine, and the nucleotide analog inhibitor adefovir dipivoxil. This review provides insights into the benefits and limitations of lamivudine and adefovir dipivoxil for the treatment of chronic hepatitis B. Lamivudine and adefovir dipivoxil have similar antiviral efficacies. Lamivudine has negligible side effects but a high rate of drug resistance, whereas adefovir dipivoxil has a low rate of drug resistance but long-term use is associated with a small risk of nephrotoxicity. Several other nucleoside and nucleotide analogs are being evaluated in phase II/III clinical trials for hepatitis B.

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

A review of entecavir in the treatment of chronic hepatitis B infection. [2014] Infection with the hepatitis B virus (HBV) affects two billion people worldwide, and an estimated 400 million people are chronically infected. Currently, FDA-approved regimens for the treatment of chronic HBV include interferon-alpha2b, peginterferon-alpha2a, lamivudine, adefovir dipivoxil, and recently, entecavir.

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] To investigate the efficacy and safety of adefovir dipivoxil (ADV, DAIDING) for Chinese chronic hepatitis B patients with lamivudine (LAM) resistance.