Long-Term Follow-Up for GSK3228836 in Hepatitis B

(B-Sure Trial)

Recruiting at 78 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must be taking: Nucleos(t)ide analogues

Disqualifiers: Other HBV studies, 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

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the long-term effects of a previous treatment for hepatitis B. It focuses on participants who responded well to an earlier study of the drug bepirovirsen (GSK3228836). Participants will be divided into groups based on whether they continued or stopped using other hepatitis B medications. This trial targets individuals who participated in specific studies with bepirovirsen and showed a good response, such as maintaining low virus levels after stopping other treatments. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

If you are currently on a stable nucleos(t)ide analogue (NA) treatment, you will need to stop taking it according to the study's cessation schedule. If you are not on NA treatment, you do not need to stop any current medications.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that bepirovirsen, the treatment under study, has generally been well-tolerated in past trials. In one study, participants took 300 mg of bepirovirsen weekly for 24 weeks. This study found that the treatment significantly reduced hepatitis B virus levels in some patients.

Most participants handled the treatment well, but some experienced side effects like headaches and tiredness, which were usually mild to moderate. Serious side effects were rare. Since these results come from a later stage of research, they suggest that bepirovirsen is fairly safe for many people.

It's important to remember that individual experiences can vary. Prospective trial participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about GSK3228836 for treating Hepatitis B because it offers a different approach from the current standard treatments like nucleos(t)ide analogues (NAs) and interferons. Unlike these traditional therapies that primarily suppress the virus, GSK3228836 aims to achieve a functional cure by targeting and reducing the production of viral proteins. This could potentially lead to a more lasting solution, reducing the need for ongoing medication. Additionally, its focus on achieving a functional cure could minimize the long-term side effects associated with prolonged use of existing treatments.

What evidence suggests that this treatment might be an effective treatment for Hepatitis B?

Research shows that bepirovirsen, the treatment under study, has potential in treating chronic Hepatitis B. In earlier studies, about 9 to 10% of participants experienced a lasting disappearance of the hepatitis B surface antigen (HBsAg) and HBV DNA after receiving the treatment. This indicates the virus became undetectable in their blood, demonstrating a strong response. The treatment has shown quick reductions in the virus, suggesting it could have long-lasting effects. The current follow-up study aims to determine if these effects can be maintained over time. Participants in this trial will be monitored for 33 months to assess the durability of these responses. ^{1 2 4 5 6}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

I am able to understand and sign the consent form.

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

Exclusion Criteria

Participants who have/or are currently participating in another non-GSK interventional clinical study exploring HBV treatment since completing their treatment with GSK3228836

Any condition which, in the opinion of the investigator or Medical Monitor, contraindicates their participation in this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Follow-up

Participants are monitored for durability of treatment response from the parent study

33 months

Extended Follow-up

Participants maintaining functional cure or partial response are followed up for an additional 2 years

24 months

What Are the Treatments Tested in This Trial?

Interventions

• GSK3228836

Trial Overview 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.

How Is the Trial Designed?

Group I: On-NA participants Experimental Treatment 2 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 participants Experimental Treatment 2 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 participants Experimental Treatment 2 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.

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

In a phase 2b trial involving 457 participants with chronic hepatitis B virus (HBV) infection, bepirovirsen treatment led to sustained loss of hepatitis B surface antigen (HBsAg) and HBV DNA in 9-10% of participants, indicating its potential efficacy as a treatment.

While bepirovirsen showed some effectiveness, it was associated with more adverse events, such as injection-site reactions and fatigue, compared to placebo, highlighting the need for further studies to evaluate its safety and long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. Yuen, MF., Lim, SG., Plesniak, R., et al.[2023]

Bepirovirsen, an antisense oligonucleotide, showed promising results in reducing hepatitis B surface antigen (HBsAg) levels with a favorable safety profile after just 4 weeks of treatment in patients with chronic hepatitis B virus (HBV) infection.

The phase 2b B-Clear study enrolled 457 participants and aims to evaluate the long-term efficacy of bepirovirsen in achieving HBsAg and HBV DNA seroclearance after treatment, comparing results in patients receiving nucleos(t)ide analog therapy versus those not on therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B-Clear Phase 2b Study Design: Establishing the Efficacy and Safety of Bepirovirsen in Patients with Chronic Hepatitis B Virus Infection. Cremer, J., Elston, R., Campbell, FM., et al.[2023]

Adefovir dipivoxil has shown sustained efficacy and safety in treating chronic hepatitis B over long-term studies of up to 5 years, making it a reliable option for patient management.

The drug is particularly effective for patients with lamivudine-resistant HBV infections and demonstrates a delayed emergence of resistance, contributing to its durable therapeutic response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in the treatment of chronic hepatitis B: long-term experience with adefovir dipivoxil. Delaney, WE.[2013]

GSK3389404, an investigational treatment for chronic hepatitis B virus (HBV) infection, demonstrated a dose-dependent reduction in hepatitis B surface antigen (HBsAg), indicating its potential to target HBV RNA and reduce viral protein production.

The study, involving 66 patients, showed that while GSK3389404 had an acceptable safety profile with no deaths reported, no effective dosing regimen was identified, as no patients achieved HBsAg seroclearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy. Yuen, MF., Heo, J., Kumada, H., et al.[2023]

Bepirovirsen, an antisense oligonucleotide targeting HBV RNA, demonstrated a favorable safety profile in a phase 2 trial involving treatment-naïve and virally suppressed individuals with chronic hepatitis B, with most adverse events being mild to moderate.

Significant reductions in hepatitis B surface antigen (HBsAg) were observed in treatment-naïve participants receiving the higher dose of bepirovirsen (300 mg), indicating potential antiviral activity that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial. Yuen, MF., Heo, J., Jang, JW., et al.[2022]

Citations

1. 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36346079/

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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04449029

NCT04449029 | A Study of GSK3228836 in Participants ... This study is intended to evaluate if treatment with GSK3228836 can achieve sustained virologic response (SVR), that is hepatitis B virus surface antigen (HBsAg) ...

4. ir.ionis.com ir.ionis.com/news-releases/news-release-details/ionis-announces-presentation-positive-phase-2b-data-chronic

Ionis announces presentation of positive Phase 2b data for ... Data from the Phase 2b B-Clear study demonstrated the potential of bepirovirsen to provide rapid reductions in hepatitis B surface antigen in ...

5. gsk.com gsk.com/en-gb/media/press-releases/gsk-receives-us-fda-fast-track-designation-for-bepirovirsen-in-chronic-hepatitis-b/

GSK receives US FDA Fast Track designation for ... Longer term efficacy and durability of response is being investigated in the B-Sure trial, which follows participants from the B-Clear study ...

6. ir.ionis.com ir.ionis.com/news-releases/news-release-details/ionis-announces-positive-data-gsks-phase-2b-clinical-study

Ionis announces positive data from GSK's Phase 2b clinical ... Patients with low baseline hepatitis B surface antigen levels responded best to treatment with bepirovirsen with 16% and 25% of patients achieving the primary ...