Bepirovirsen for Chronic Hepatitis B

(B-Well 1 Trial)

Recruiting at 182 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

981 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Bepirovirsen for chronic hepatitis B?

Research shows that Bepirovirsen, an antisense oligonucleotide, significantly reduces hepatitis B surface antigen levels in patients with chronic hepatitis B, especially at a 300 mg dose, compared to a placebo. It also has a favorable safety profile, with most side effects being mild or moderate. ^{1 2 3 4 5}

How is the drug Bepirovirsen different from other treatments for chronic hepatitis B?

Bepirovirsen is unique because it is an antisense oligonucleotide, which means it targets and reduces all hepatitis B virus messenger RNAs, leading to a decrease in viral proteins. This mechanism is different from standard treatments like nucleos(t)ide analogs and pegylated interferons, which have low cure rates. ^{1 2 3 6 7}

What is the purpose of this trial?

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.

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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]

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]

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]

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

Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial. [2022]

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

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

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

Treatments for hepatitis B. [2006]

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

Current Antiviral Therapy of Chronic Hepatitis B: Efficacy and Safety. [2021]

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

Making safe sense of an anti-sense! [2022]

7. England pubmed.ncbi.nlm.nih.gov

Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B. [2022]