AB-729 + Pegylated Interferon for Chronic Hepatitis B

No longer recruiting at 22 trial locations

Overseen By Arbutus Biopharma

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Arbutus Biopharma Corporation

Must be taking: TAF, TDF, ETV

Disqualifiers: Hepatitis A, C, D, E, HIV, 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: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for chronic hepatitis B, a long-term liver infection. Researchers aim to determine if combining the drug AB-729 with ongoing therapy called NA, along with short courses of Peg-IFNα-2a (a type of interferon), is safe and effective in reducing the virus. Participants will be randomly assigned to groups receiving different combinations of these treatments. Ideal candidates have had hepatitis B for at least six months, are already on certain medications, and have specific virus levels in their blood. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial requires participants to continue their existing NA therapy (nucleos(t)ide analog therapy) like TAF, TDF, or ETV.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown promising results for AB-729. Patients using AB-729 experienced increases in certain immune cells, which is encouraging. However, some patients had temporary increases in liver enzymes, known as ALT flares. These flares can indicate liver stress or irritation, but they were short-lived.

Peg-IFNα-2a is already used to treat chronic hepatitis B, and its safety is well-established. Research shows it can help lower hepatitis B virus levels in the body. Common side effects include flu-like symptoms, tiredness, and mood changes, though these vary by person.

Overall, both treatments are generally considered safe, but like all medicines, they can have potential side effects. It's important to consider these when thinking about joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AB-729 for chronic hepatitis B because it takes a unique approach by combining an RNA interference (RNAi) mechanism with pegylated interferon. Unlike traditional treatments like nucleos(t)ide analogs, which primarily suppress the virus, AB-729 targets and reduces the production of viral proteins, potentially leading to better long-term outcomes. Furthermore, by combining AB-729 with pegylated interferon, this treatment might enhance the immune response, offering a more robust way to control or even clear the virus. This combination could provide a more comprehensive strategy than existing options, which often require lifelong treatment.

What evidence suggests that this trial's treatments could be effective for chronic hepatitis B?

Research has shown that AB-729, a treatment in this trial, helps lower HBsAg, a marker of hepatitis B infection, in people with chronic hepatitis B. This reduction in HBsAg levels can persist for up to 28 weeks after stopping the treatment. Pegylated interferon alpha-2a (Peg-IFNα-2a), another treatment option in this trial, significantly reduces the virus, with some patients having no detectable virus in their blood. Together, these treatments in different trial arms aim to provide a strong response to help manage chronic hepatitis B. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

My recent health checks show no major concerns.

Chronic hepatitis B virus infection with documentation at least 6 months prior to screening

Exclusion Criteria

I have been treated with experimental HBV drugs.

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

Evidence of co-infection with hepatitis A, C, D or E virus or human immunodeficiency virus (HIV) at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AB-729 60 mg SC every 8 weeks with NA for 24 weeks, followed by randomization to different treatment regimens

24 weeks

Randomized Treatment

Participants are randomized to receive either NA + Peg-IFNα-2a 180 mcg SC every week for 12 or 24 weeks, or AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 12 or 24 weeks

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AB-729
• Peg-IFNα-2a

Trial Overview 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.

How Is the Trial Designed?

Group I: Cohort B, Group 2 Experimental Treatment 2 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 1 Experimental Treatment 2 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 2 Experimental Treatment 2 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 1 Experimental Treatment 2 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.

Who Is Running the Clinical Trial?

Arbutus Biopharma Corporation

Lead Sponsor

Trials

13

Recruited

660+

Published Research Related to This Trial

In a study of 16 HBeAg-positive hepatitis B patients with lamivudine resistance, pegylated interferon-alpha treatment resulted in a 12.5% seroconversion rate, indicating limited efficacy in this resistant population.

Despite a significant reduction in viral load during treatment, levels rebounded after cessation, suggesting that pegylated interferon-alpha may only be beneficial for patients with low levels of mutant virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of pegylated interferon-alpha on the treatment of lamivudine resistant chronic HBeAg positive hepatitis B virus infection. Leemans, WF., Flink, HJ., Janssen, HL., et al.[2018]

In a study of 72 patients with chronic hepatitis B, PEG-IFN alpha-2a demonstrated significantly higher rates of HBeAg negative cases and lower HBV DNA levels compared to the control group receiving standard interferon alpha after 48 weeks of treatment.

PEG-IFN alpha-2a not only effectively inhibited HBV replication but also showed lasting effects after treatment, with no significant changes in liver inflammation or fibrosis, and was well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pegylated interferon alpha 2a in treating chronic hepatitis B patients]. Tian, YL., Zhao, W., Shen, L., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12038417/

Drug development for chronic hepatitis B functional cure Results revealed that 26% (10/39) of patients experienced a reduction in HBsAg levels (> 0.1 Log10 IU/mL) after 24 weeks of Selgantolimod ...

2. 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 ... The data indicated that Group C participants receiving nivolumab experienced increased rates of HBsAg loss (defined as HBsAg <LLOQ [0.05 IU/mL])

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04820686

NCT04820686 | A Study Evaluating Treatment Regimens ... The purpose of this study is to determine if vebicorvir (VBR, ABI-H0731) in combination with AB-729 is safe and effective in participants with chronic ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2210027

Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B ... In this phase 2b trial, bepirovirsen at a dose of 300 mg per week for 24 weeks resulted in sustained HBsAg and HBV DNA loss in 9 to 10% of participants with ...

5. arbutusbio.gcs-web.com arbutusbio.gcs-web.com/news-releases/news-release-details/arbutus-announces-new-data-ab-729-late-breaker-poster

Arbutus Announces New Data on AB-729 in Late Breaker ... ... Effective at Reducing HBsAg in Patients with Chronic Hepatitis B. HBsAg remains suppressed up to 28 weeks after discontinuation of AB-729.

6. investor.arbutusbio.com investor.arbutusbio.com/news-releases/news-release-details/arbutus-announces-robust-hbsag-decline-data-ab-729-dosed-60-mg

Arbutus Announces Robust HBsAg Decline Data with AB-729 ... Repeat dosing of 60 mg AB-729 every 8 weeks resulted in mean HBsAg declines of –1.37 log10 (N=6) comparable to AB-729 dosed every 4 weeks ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9293617/

RNA interference as a novel treatment strategy for chronic ... Patients on AB-729 had an increase in interferon-gamma producing HBV specific T-cells and had transient alanine aminotransferase (ALT) flares that correlated ...

8. hub.hku.hk hub.hku.hk/handle/10722/305532

Safety and pharmacodynamics of the GALNAC-siRNA AB ... Here we report preliminary safety and pharmacodynamic (PD) results following administration of AB-729 in subjects with chronic hepatitis B (CHB) ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06245291

NCT06245291 | Study of Imdusiran (AB-729) in ... This is a phase 2a, open-label, multicenter study investigating the safety, tolerability, and antiviral activity of durvalumab administered at targeted times.

10. anzctr.org.au anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000295943

ANZCTR - Registration Examples of known/possible adverse reactions/events: This is a first in human study, so limited safety information about AB-729 is available. Possible adverse ...