AB-729 + Pegylated Interferon for Chronic Hepatitis B

Recruiting at 17 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

43 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug AB-729 + Peg-IFNα-2a for treating chronic hepatitis B?

Research shows that pegylated interferon alpha-2a (Peg-IFNα-2a) is effective in treating chronic hepatitis B, with studies indicating it can lead to positive responses in a significant number of patients. This suggests that combining it with AB-729 could potentially enhance treatment outcomes for chronic hepatitis B. ^{1 2 3 4 5}

Is the combination of AB-729 and Pegylated Interferon safe for humans?

Pegylated Interferon (Peg-IFN) has been studied for safety in treating chronic hepatitis B, showing it is generally safe for patients, including children and adolescents. ^{2 3 6 7 8}

How is the drug AB-729 + Pegylated Interferon unique for treating chronic hepatitis B?

AB-729 combined with Pegylated Interferon is unique because it potentially offers a new approach by combining a novel agent (AB-729) with an established treatment (Pegylated Interferon), which may enhance the effectiveness of the therapy for chronic hepatitis B compared to using Pegylated Interferon alone. ^{1 2 5 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of pegylated interferon-alpha on the treatment of lamivudine resistant chronic HBeAg positive hepatitis B virus infection. [2018]

2. China pubmed.ncbi.nlm.nih.gov

[Pegylated interferon alpha 2a in treating chronic hepatitis B patients]. [2018]

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

Peginterferon alfa-2b as monotherapy or in combination with lamivudine in patients with HBeAg-negative chronic hepatitis B: a randomised study. [2018]

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

A baseline tool for predicting response to peginterferon alfa-2a in HBeAg-positive patients with chronic hepatitis B. [2022]

5. England pubmed.ncbi.nlm.nih.gov

48 weeks pegylated interferon alpha-2a is superior to 24 weeks of pegylated interferon alpha-2b in achieving hepatitis B e antigen seroconversion in chronic hepatitis B infection. [2018]

6. Turkey pubmed.ncbi.nlm.nih.gov

Safety of peginterferon alfa-2a (40KD) treatment in patients with chronic hepatitis B infection: an observational, multicenter, open label, non-interventional study in Turkish patients. [2018]

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

Efficacy and Safety of Pegylated Interferon for the Treatment of Chronic Hepatitis B in Children and Adolescents: A Systematic Review and Meta-analysis. [2021]

8. Poland pubmed.ncbi.nlm.nih.gov

Virological response to treatment with peginterferon alfa-2a in adolescents with chronic hepatitis B. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Peginterferon α in the treatment of chronic hepatitis B. [2023]

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

Ultra-Long-term Follow-up of Interferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B Virus Infection. [2021]