Bepirovirsen for Chronic Hepatitis B

(B-Well 2 Trial)

Not currently recruiting at 218 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new treatment, bepirovirsen, can effectively manage chronic Hepatitis B by reducing the virus's presence in the body. Participants will receive either bepirovirsen or a placebo to evaluate the treatment's effectiveness over time. It targets individuals who have had chronic Hepatitis B for at least six months, are managing it with stable medication, and have specific virus levels in their blood. The trial aims to confirm the safety and lasting effects of bepirovirsen as a treatment option. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that bepirovirsen has been tested for safety in people with chronic hepatitis B. In earlier studies, most patients tolerated the treatment well. Some experienced side effects, usually mild, such as temporary reactions at the injection site or mild flu-like symptoms.

The FDA has granted the treatment Fast Track status, indicating its promise and safety in earlier research. However, as with any new treatment, monitoring for side effects remains important. Overall, current evidence suggests that bepirovirsen is a promising option with manageable safety concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Bepirovirsen is unique because it targets the RNA of the hepatitis B virus, potentially reducing viral replication more effectively than current treatments, which primarily focus on suppressing the virus with nucleos(t)ide analogs like tenofovir and entecavir. Unlike these standard treatments, Bepirovirsen aims to eliminate the virus by silencing its genetic material, offering hope for a functional cure. Researchers are excited because this innovative approach could lead to a significant breakthrough in managing chronic hepatitis B, moving beyond mere viral suppression to potentially clearing the infection.

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. One study found that 29% of patients not on other hepatitis B medications had very low levels of the virus and its surface protein in their blood after 24 weeks of taking bepirovirsen. Another study found that 9 to 10% of participants experienced lasting reductions in these levels. Bepirovirsen works by slowing the virus's ability to multiply and reducing the amount of the virus's surface protein in the blood. These results suggest that bepirovirsen could be effective for people with chronic hepatitis B, especially those who start with lower levels of the virus's surface protein. ^{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 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 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 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

What Are the Treatments Tested in This Trial?

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.

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]

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]

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 ...