What is the mechanism of action of this treatment?

The most common treatments for Chronic Hepatitis B (CHB) include nucleos(t)ide analogues and antisense oligonucleotides. Nucleos(t)ide analogues, such as entecavir and tenofovir, inhibit the reverse transcriptase enzyme, essential for HBV DNA replication, thereby reducing viral load and liver inflammation. Antisense oligonucleotides, like Bepirovirsen, target HBV mRNA to prevent the production of viral proteins necessary for the virus's life cycle, reducing both viral antigenemia and viremia. These mechanisms are crucial for CHB patients as they help in selecting effective treatments, leading to better long-term outcomes and reduced liver damage.

What side effects are associated with this type of intervention?

Common treatments for Chronic Hepatitis B, such as entecavir, lamivudine, tenofovir, and pegylated interferon, have various side effects. Entecavir and tenofovir are generally well-tolerated but can cause headaches, fatigue, dizziness, and gastrointestinal issues. Lamivudine can lead to similar side effects and has a higher risk of developing drug resistance. Pegylated interferon may cause flu-like symptoms, depression, and hematologic abnormalities. Antisense oligonucleotides like bepirovirsen, which target HBV mRNA, are still under investigation, but potential side effects could include injection site reactions, flu-like symptoms, and liver enzyme elevations.

What prior FDA approvals exist?

The FDA has approved several treatments for Chronic Hepatitis B, including nucleos(t)ide analogues like entecavir and tenofovir, which are known for their potent antiviral activity and low resistance rates in treatment-naïve patients. Entecavir, for instance, is effective in reducing HBV DNA levels and improving liver histology. However, it is less effective in patients with lamivudine-resistant HBV. Tenofovir is preferred in such cases due to its efficacy against resistant strains. While Bepirovirsen, an antisense oligonucleotide targeting HBV mRNA, is still under study, it represents a novel approach compared to these traditional nucleos(t)ide analogues.

What other types of research exist?

Promising novel alternatives to Bepirovirsen for Chronic Hepatitis B patients include: 1) Pegylated Interferon (PegIFN) combined with nucleos(t)ide analogues, which has shown improved HBeAg and HBsAg loss rates. 2) Telbivudine-based optimization strategies, particularly for HBeAg-negative patients, which have demonstrated efficacy in long-term viral suppression. 3) SATE pronucleotide derivatives of acyclovir, which have shown potent anti-HBV activity in preclinical models. These alternatives offer different mechanisms of action and have shown potential in clinical and preclinical studies.

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Antisense Oligonucleotide

Bepirovirsen for Chronic Hepatitis B (B-Well 1 Trial)

Phase 3

Waitlist Available

Research Sponsored by GlaxoSmithKline

Eligibility Criteria Checklist

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

Must have

Are you over 18 years old?

Have you been diagnosed with chronic hepatitis B virus infection for at least 6 months?

Must not have

Have you taken any interferon-containing therapy (for example, Pegasys or Peg-Intron) within the past 12 months?

Have you had major surgery within the past 3 months?

Timeline

Screening 60 days

Treatment 24 weeks

Follow Up 48 weeks

Awards & highlights

Pivotal Trial

Summary

This trial is testing bepirovirsen, a medication that aims to lower a key protein made by the hepatitis B virus. Bepirovirsen has shown reductions in viral components in cell culture and animal models. It targets patients with specific levels of this protein in their blood. The goal is to see if bepirovirsen can better control the infection compared to current treatments.

Who is the study for?

This trial is for adults with chronic Hepatitis B who've been on stable antiviral therapy for at least 6 months, have low liver enzymes, and controlled virus levels. They must be willing to potentially stop their usual medication as part of the study. People with cirrhosis, recent cancer (except certain skin cancers), other significant health issues, or co-infections like HIV are not eligible.

What is being tested?

The trial tests Bepirovirsen's ability to suppress Hepatitis B surface antigen compared to a placebo over 24 weeks. Participants will also continue their standard antiviral drugs during some phases and may stop them in others to assess long-term effects up to approximately 104 weeks.

What are the potential side effects?

Potential side effects of Bepirovirsen aren't detailed here but could include typical drug reactions such as injection site discomfort, flu-like symptoms, fatigue, or more serious immune-related events given its nature as an antiviral agent.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am over 18 years old.

Exclusion Criteria

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

Timeline

Screening ~ 60 days1 visit

Treatment ~ 24 weeks1 visit

Follow Up ~ 48 weeks1 visit

Screening ~ 60 days

Treatment ~ 24 weeks

Follow Up ~48 weeks

This trial's timeline: 60 days for screening, 24 weeks for treatment, and 48 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of participants achieving functional cure (FC) with baseline HBsAg ≤3000 IU/mL

Secondary study objectives

Number of participants achieving FC with baseline HBsAg ≤1000 IU/mL

Number of participants achieving sustained suppression of HBV DNA (<LLOQ) with baseline HBsAg ≤1000 IU/mL

Number of participants achieving sustained suppression of HBV DNA (<LLOQ) with baseline HBsAg ≤3000 IU/mL

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: BepirovirsenExperimental Treatment1 Intervention

Group II: PlaceboPlacebo Group1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bepirovirsen

2023

Completed Phase 1

~160

0 / 14Eligibility 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 analogues and antisense oligonucleotides. Nucleos(t)ide analogues, such as entecavir and tenofovir, inhibit the reverse transcriptase enzyme, essential for HBV DNA replication, thereby reducing viral load and liver inflammation. Antisense oligonucleotides, like Bepirovirsen, target HBV mRNA to prevent the production of viral proteins necessary for the virus's life cycle, reducing both viral antigenemia and viremia. These mechanisms are crucial for CHB patients as they help in selecting effective treatments, leading to better long-term outcomes and reduced liver damage.

In vivo reduction of hepatitis B virus antigenemia and viremia by antisense oligonucleotides.