What is the mechanism of action of this treatment?

The most common treatments for Chronic Hepatitis B (CHB) include nucleos(t)ide analogs and RNA interference (RNAi) therapeutics. Nucleos(t)ide analogs, such as tenofovir and entecavir, inhibit the reverse transcriptase enzyme, essential for HBV DNA replication, thereby reducing viral load and liver damage. RNAi therapeutics, like AB-729, target HBV genes by degrading viral RNA, preventing the production of viral proteins and replication. These mechanisms are crucial for CHB patients as they help lower viral load, limit liver damage, and improve long-term health outcomes.

What side effects are associated with this type of intervention?

Common treatments for Chronic Hepatitis B, such as nucleos(t)ide analogs (e.g., entecavir, tenofovir) and pegylated interferon, have known side effects. Nucleos(t)ide analogs are generally well-tolerated but can cause kidney dysfunction and bone mineral density loss, particularly with long-term use. Pegylated interferon can lead to flu-like symptoms, fatigue, depression, and hematologic abnormalities such as neutropenia and thrombocytopenia. Both treatments require careful monitoring to manage these potential adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Chronic Hepatitis B, primarily focusing on nucleos(t)ide analogs such as entecavir and tenofovir. Entecavir is known for its potent antiviral activity and low resistance rate in nucleos(t)ide-naïve patients, while tenofovir is effective for both treatment-naïve patients and those with resistance to other antivirals like lamivudine. These treatments work by inhibiting viral replication, similar to the mechanism of action being explored in the AB-729 trial, which targets HBV genes through RNA interference.

What other types of research exist?

Promising novel alternatives to AB-729 for Chronic Hepatitis B patients in 2024 include: 1) Combination therapy with lamivudine and pegylated interferon alfa-2a, which has shown enhanced antiviral effects and higher rates of HBsAg loss compared to monotherapy. 2) Pegylated interferon alfa-2a monotherapy, particularly for extended durations (up to 96 weeks), which has demonstrated sustained virological responses. 3) AB-506, a capsid inhibitor that has shown potent antiviral activity in early-phase studies. These alternatives offer different mechanisms of action and may be considered based on individual patient profiles and treatment goals.

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Nucleos(t)ide Analogue

AB-729 + Pegylated Interferon for Chronic Hepatitis B

Phase 2

Waitlist Available

Research Sponsored by Arbutus Biopharma Corporation

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects must have been receiving either TAF, TDF (or equivalent), or ETV consistently for ≥12 months prior to dosing Day 1

Be between 18 and 65 years old

Must not have

Previous treatment with an experimental HBV-directed RNA-interference or antisense oligonucleotide product

History of any clinically significant medical condition associated with chronic liver disease, cirrhosis, evidence of decompensated liver disease, or findings suggestive of hepatocellular carcinoma (HCC) at any time

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called AB-729 for patients with Chronic Hepatitis B. It is used along with existing treatments to lower virus levels, manage the virus, and boost the immune system.

Who is the study for?

This trial is for adults with chronic hepatitis B who've been on specific antiviral drugs for at least a year, have low HBV DNA levels, are HBeAg-negative, and have liver scarring within safe limits. It's not open to those with other viral infections like HIV or conditions suggesting advanced liver disease.

What is being tested?

The study tests the safety and virus-fighting ability of AB-729 combined with ongoing antiviral therapy and short courses of Peg-IFNα-2a in people with chronic hepatitis B. Participants will be chosen randomly to receive this combination treatment.

What are the potential side effects?

Potential side effects may include flu-like symptoms, fatigue, headache, fever from Peg-IFNα-2a; AB-729's side effects aren't fully known but could involve reactions at the injection site or changes in liver enzymes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been on TAF, TDF, or ETV for at least 12 months.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with experimental HBV drugs.

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I have a history of serious liver disease or signs of liver cancer.

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I cannot use or self-administer Peg-IFNα-2a due to health reasons.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Cohort B, Group 2Experimental Treatment2 Interventions

AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks.

Group II: Cohort B, Group 1Experimental Treatment2 Interventions

AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks.

Group III: Cohort A, Group 2Experimental Treatment2 Interventions

AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks.

Group IV: Cohort A, Group 1Experimental Treatment2 Interventions

AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks.

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Chronic Hepatitis B (CHB) include nucleos(t)ide analogs and RNA interference (RNAi) therapeutics. Nucleos(t)ide analogs, such as tenofovir and entecavir, inhibit the reverse transcriptase enzyme, essential for HBV DNA replication, thereby reducing viral load and liver damage. RNAi therapeutics, like AB-729, target HBV genes by degrading viral RNA, preventing the production of viral proteins and replication. These mechanisms are crucial for CHB patients as they help lower viral load, limit liver damage, and improve long-term health outcomes.