Bepirovirsen for Chronic Hepatitis B

(B-Well 1 Trial)

Not currently recruiting at 203 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must be taking: Nucleos(t)ide analogues

Must not be taking: Immunosuppressants, Interferons, Anticoagulants, others

Disqualifiers: Liver disease, HIV, Cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates whether the new drug bepirovirsen is safe and effective for individuals with chronic hepatitis B, a liver infection. The study compares bepirovirsen to a placebo (a look-alike pill with no active drug) over several stages to determine if it can reduce virus levels and be safely discontinued after a period. It is suitable for those who have had chronic hepatitis B for at least six months, are on stable medication, and have a specific virus level in their blood. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial requires participants to stop their nucleos(t)ide analogue (NA) treatment at a certain stage, but it does not specify about other medications. If you are on anticoagulation therapies, you may need to stop them, but this will be decided by the investigator.

Is there any evidence suggesting that bepirovirsen is likely to be safe for humans?

Research shows that bepirovirsen has been tested in people with long-term hepatitis B, yielding promising results. Studies have found that most patients tolerate it well. Some people have experienced side effects, but these are usually mild. Importantly, past studies have not directly linked any serious health problems to the drug.

While this is encouraging, bepirovirsen remains under investigation. Ongoing research ensures that any safety issues are identified and addressed. For those considering joining a trial, this means a substantial amount of safety information is already available, with more being collected to confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Bepirovirsen is unique because it targets the hepatitis B virus differently from current treatments like nucleoside analogs and interferons. Most treatments work by suppressing the virus's replication, but Bepirovirsen is designed to directly target and degrade the viral RNA, potentially reducing the virus's ability to produce proteins necessary for its survival. Researchers are excited about this approach as it offers a new mechanism of action that could lead to more effective management of chronic hepatitis B, possibly with fewer side effects.

What evidence suggests that bepirovirsen might be an effective treatment for chronic hepatitis B?

Research has shown that bepirovirsen, which participants in this trial may receive, may help treat chronic hepatitis B. An earlier study demonstrated that bepirovirsen reduced the activity of the hepatitis B virus and lowered the amount of a specific virus protein in the blood. In that study, 29% of patients not on other treatments had no detectable virus markers after 24 weeks. Another study found that 9 to 10% of participants maintained this loss of virus markers with bepirovirsen treatment. These findings suggest that bepirovirsen could be effective for people with chronic hepatitis B, especially those who start with lower levels of the virus. ^{1 2 4 6 7}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Alanine aminotransferase (ALT) ≤2 × upper limit of normal (ULN).

Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL.

Plasma or serum HBsAg concentration >100 IU/mL, but no greater than ≤3000 IU/mL.

Exclusion Criteria

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

You have been diagnosed with Liver Disease

Have you had major surgery within the past 3 months?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Double-blind Treatment

Participants receive either bepirovirsen or placebo for 24 weeks

24 weeks

Nucleos(t)ide Analogue Treatment

Participants continue with nucleos(t)ide analogue treatment for 24 weeks

24 weeks

NA Cessation or Continuation

Participants either cease or continue NA treatment for an additional 24 weeks

24 weeks

Durability and Follow-up

Participants are monitored for durability of response and follow-up for 24 weeks after stopping NA treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bepirovirsen
• Placebo

Trial Overview

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.

How Is the Trial Designed?

Group I: Bepirovirsen Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

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

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]

Besifovir at doses of 90 mg and 150 mg daily showed similar effectiveness to entecavir 0.5 mg daily in suppressing HBV DNA in chronic hepatitis B patients after 48 weeks, with no significant differences in treatment outcomes.

The main side effect of besifovir was a decrease in serum L-carnitine levels in 94.1% of patients, which was manageable with carnitine supplementation, indicating a generally safe profile for the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B. Lai, CL., Ahn, SH., Lee, KS., et al.[2022]

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]

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]

Citations

1.

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 ...

2.

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 ...

Bepirovirsen inhibits the replication of viral DNA in the body, suppresses the level of hepatitis B surface antigen (HBsAg) in the blood, and ...

3.

ir.ionis.com

ir.ionis.com/news-releases/news-release-details/ionis-announces-gsk-has-advanced-bepirovirsen-phase-3

Ionis announces GSK has advanced bepirovirsen into ...

Bepirovirsen is a potential first-in-class treatment for CHB, uniquely designed to simultaneously reduce hepatitis B virus (HBV) replication and suppress viral ...

4.

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 ...

5.

gsk.com

gsk.com/en-gb/media/press-releases/gsk-presents-promising-new-data-for-bepirovirsen-an-investigational-treatment-for-chronic-hepatitis-b/

GSK presents promising new data for bepirovirsen, an ...

For patients not on NA (n=230), 24 weeks treatment of 300 mg bepirovirsen resulted in HBsAg < LLOQ and HBV DNA < LLOQ in 29% of patients at end ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8516644/

Safety, tolerability and antiviral activity of the antisense ...

Chronic infection with hepatitis B virus (HBV) leads to an increased risk of death from cirrhosis and hepatocellular carcinoma.

7.

natap.org

natap.org/2024/HBV/081224_01.htm

GSK receives US FDA Fast Track designation ...

Bepirovirsen is the only single agent in phase III development that has shown the potential to achieve clinically meaningful functional cure ...