Long-Term Follow-Up for GSK3228836 in Hepatitis B

(B-Sure Trial)

Recruiting at 67 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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug GSK3228836 (Bepirovirsen) in treating chronic hepatitis B?

Research shows that Bepirovirsen, an antisense oligonucleotide, significantly reduces hepatitis B surface antigen levels in patients with chronic hepatitis B, especially in those who are treatment-naïve. It has a favorable safety profile, with most side effects being mild or moderate. ^{1 2 3 4 5}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. United States 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. [2023]

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

Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. [2023]

3. Netherlands 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. [2023]

4. United States 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. [2022]

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

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