Bepirovirsen for Chronic Hepatitis B

(B-Well 2 Trial)

Recruiting at 188 trial locations

Overseen By EU 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

Disqualifiers: Liver cirrhosis, Hepatitis C, HIV, 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

871 Participants Needed

Trial Summary

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.

Do I need to stop my current medications for the trial?

The trial requires participants to be on a stable nucleos(t)ide analogue (NA) therapy without changes for at least 6 months before and during the study. Participants must be willing to stop their NA treatment according to the study protocol, but the protocol does not specify about other medications.

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

Research shows that Bepirovirsen, a type of drug that targets the virus's genetic material, can significantly reduce the levels of hepatitis B virus proteins in the blood, especially in patients who have not been treated before. This suggests it may be effective in managing chronic hepatitis B. ^{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 functional cure rates. ^{1 2 3 6 7}

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 viral DNA levels in their blood, and normal to slightly elevated liver enzymes. They must not have other infections like HIV or Hepatitis C/D, no recent cancer except certain skin cancers, and can't be on immune-suppressing drugs or have a history of drug abuse.

Inclusion Criteria

I am willing to stop my current NA treatment as required.

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

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

Exclusion Criteria

I cannot take immunosuppressive treatments or high doses of steroids.

I have taken interferon therapy in the last 12 months.

I have or might have liver cirrhosis.

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 receive nucleos(t)ide analogue treatment for 24 weeks

24 weeks

NA Cessation or Continuation

Participants either cease or continue NA treatment for 24 weeks

24 weeks

Durability and Follow-up

Participants are monitored for durability of response and follow-up for 24 weeks

24 weeks

Treatment Details

Interventions

• Bepirovirsen
• Placebo

Trial Overview The study tests the effectiveness of Bepirovirsen compared to a placebo in suppressing the hepatitis B virus when taken alongside standard antiviral treatment. It's divided into stages including initial double-blind treatment, continued antiviral therapy, potential cessation of antivirals, and monitoring durability of response over approximately two years.

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. England pubmed.ncbi.nlm.nih.gov

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

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

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