What is the mechanism of action of this treatment?

Common treatments for Hepatitis B, such as nucleos(t)ide analogs like entecavir and tenofovir, work by inhibiting the viral polymerase enzyme, which is crucial for viral DNA replication. This suppression of viral replication helps reduce the viral load in the patient's body, thereby limiting liver damage and reducing the risk of liver cancer. Investigational agents like GSK3228836 target HBV RNA, leading to reduced production of viral proteins, which may enhance the immune system's ability to control the virus. Understanding these mechanisms is vital for patients as it highlights the importance of these treatments in managing the disease and preventing severe complications.

What side effects are associated with this type of intervention?

Common treatments for Hepatitis B, such as nucleos(t)ide analogs (e.g., entecavir, tenofovir) and interferon-based therapies, have well-documented side effects. Nucleos(t)ide analogs are generally well-tolerated but can cause kidney dysfunction and bone mineral density loss. Interferon-based therapies often result in flu-like symptoms, fatigue, depression, and hematologic abnormalities. For investigational agents like GSK3228836, which targets HBV RNA, the safety profile is still being established, but early studies indicate an acceptable safety profile with dose-dependent reductions in HBsAg. Common side effects across these treatments include gastrointestinal disturbances, headache, and potential liver enzyme elevations.

What prior FDA approvals exist?

The FDA has approved several antiviral agents for the treatment of Hepatitis B, including nucleoside and nucleotide analogs such as tenofovir, entecavir, lamivudine, and adefovir dipivoxil. These drugs work by inhibiting the replication of the Hepatitis B virus. Tenofovir and entecavir are often preferred due to their potent antiviral activity and low rates of drug resistance. Additionally, pegylated interferon alfa-2a has been approved and is used for its immunomodulatory effects, which help in achieving sustained virologic response. These treatments aim to reduce HBV DNA levels, normalize liver enzymes, and promote seroconversion of hepatitis B e antigen (HBeAg).

What other types of research exist?

Promising novel alternatives to GSK3228836 for Hepatitis B treatment include RO7062931, an N-acetylgalactosamine-conjugated single-stranded oligonucleotide targeting HBV RNA, and GSK3389404 (Bepirovirsen), an antisense oligonucleotide targeting pregenomic and mRNA transcripts of HBV. Both have shown potential in clinical trials, with RO7062931 demonstrating targeted liver delivery and GSK3389404 showing dose-dependent HBsAg reductions.

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Virus Therapy

Long-Term Follow-Up for GSK3228836 in Hepatitis B (B-Sure Trial)

Phase 2

Recruiting

Research Sponsored by GlaxoSmithKline

Eligibility Criteria Checklist

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

Must have

Participants who have previously received at least one dose of GSK3228836 and achieved SVR (defined as HBsAg and HBV DNA < lower limit of quantification (LLOQ) from end of previous investigational treatment until the End of study (EoS) visit in the previous treatment study (complete responder)

Capable of giving signed informed consent

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from primary endpoint assessment in the parent study up to month 57

Summary

This trial is checking the duration of benefits for people who previously took the medication GSK3228836 and showed improvement. No new treatment will be given during this study.

Who is the study for?

This trial is for people who have had Hepatitis B and were previously treated with GSK3228836, achieving full or partial virus control. They must be able to stop their current antiviral meds as per the study's schedule and give informed consent. Those in other HBV studies or with conditions that make participation risky can't join.

What is being tested?

The study isn't testing a new treatment; instead, it's checking how long the effects of GSK3228836 last in patients who've already taken it. It looks at whether they maintain low levels of hepatitis B surface antigen (HBsAg) and DNA without further doses.

What are the potential side effects?

Since no additional GSK3228836 will be given in this follow-up study, there are no direct side effects being tested. However, participants' health will be monitored for any late-occurring effects from their previous treatment.

Eligibility Criteria

Inclusion Criteria

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

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I've had a successful treatment with GSK3228836 for hepatitis B.

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I am able to understand and sign the consent form.

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I have had GSK3228836 before and it partially worked for me.

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I am willing to stop my current NA treatment if required by the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from primary endpoint assessment in the parent study up to month 57

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from primary endpoint assessment in the parent study up to month 57

This trial's timeline: 3 weeks for screening, Varies for treatment, and from primary endpoint assessment in the parent study up to month 57 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Percentage of Not-on-NA participants without loss of parent study (PSPO)

Trial Design

3Treatment groups

Experimental Treatment

Group I: On-NA participantsExperimental Treatment2 Interventions

Participants rolling over from studies 209668, 209348, 212602, 202009, 219288, and 217023 who entered the parent study on stable NA therapy and remained on NA therapy for the duration of the treatment and follow-up periods in the parent study will be included in this arm. NA cessation will occur at 3 months in 206882 for eligible and willing participants. Participants will be followed up for 33 months. Participants rolling over from studies 209668 and 209348 who stopped NA treatment and are maintaining either FC or a partial response at Month 33, and remaining off NA treatment, will be eligible to be followed up for an additional 2 years. No study treatment will be administered in this study.

Group II: Not-on-NA participantsExperimental Treatment2 Interventions

Participants rolling over from study 209668 who have not received nucleos(t)ide analogue (NA) therapy during the parent study and remain off NAs will be included in this arm. Participants will be followed up for 33 months. Participants maintaining either functional cure (FC) or a partial response off NA treatment at Month 33 will be eligible to be followed up for an additional 2 years. No study treatment will be administered in this study.

Group III: NA-cessated participantsExperimental Treatment2 Interventions

Participants rolling over from studies 202009 and 219288 who have stopped NA treatment during the parent study will be included in this arm. Participants will be followed up for 33 months. No study treatment will be administered in this study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bepirovirsen

2023

Completed Phase 1

~160

Placebo

1995

Completed Phase 3

~2670

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

Common treatments for Hepatitis B, such as nucleos(t)ide analogs like entecavir and tenofovir, work by inhibiting the viral polymerase enzyme, which is crucial for viral DNA replication. This suppression of viral replication helps reduce the viral load in the patient's body, thereby limiting liver damage and reducing the risk of liver cancer. Investigational agents like GSK3228836 target HBV RNA, leading to reduced production of viral proteins, which may enhance the immune system's ability to control the virus. Understanding these mechanisms is vital for patients as it highlights the importance of these treatments in managing the disease and preventing severe complications.

Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy.Replication of clinical hepatitis B virus isolate and its application for selecting antiviral agents for chronic hepatitis B patients.