Bepirovirsen for HIV and Hepatitis B

(B-Focus Trial)

Recruiting at 53 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must be taking: Antiretrovirals

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

Disqualifiers: Liver cirrhosis, Hepatocellular carcinoma, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called bepirovirsen for individuals living with both HIV and hepatitis B. The goal is to determine if bepirovirsen is safe and more effective than a placebo (a non-active treatment) in managing these infections. Suitable candidates for this trial have had both HIV and hepatitis B for over a year, are on a stable HIV treatment plan, and have well-controlled virus levels. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

You must continue your current antiretroviral therapy (ART) with tenofovir and lamivudine or emtricitabine. Some medications, like immunosuppressants and anticoagulants, may need to be stopped. The protocol does not specify a washout period for other medications.

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

Research has shown that bepirovirsen has undergone safety testing in several studies. One study demonstrated that bepirovirsen led to a dose-dependent reduction in hepatitis B surface antigen levels, meaning that higher doses resulted in a greater decrease in these virus markers. Although the study focused on efficacy, its progression to further trials suggests good tolerance.

Additionally, the FDA has given bepirovirsen a Fast Track designation for chronic hepatitis B, indicating promise in early trials, including safety.

Overall, while specific side effects were not detailed, the advancement of bepirovirsen into further studies often indicates no major safety concerns so far. Participants should always discuss potential risks with study coordinators to fully understand what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Bepirovirsen is unique because it targets both HIV and Hepatitis B, which is different from most current treatments that focus on just one of these viruses. It works by using antisense oligonucleotides, which are short strands of nucleic acids designed to bind to specific RNA sequences in the viruses, potentially reducing their ability to replicate. This mechanism of action sets it apart from traditional treatments like antiretroviral therapy for HIV and nucleos(t)ide analogues for Hepatitis B, which primarily prevent the viruses from multiplying. Researchers are excited about bepirovirsen because it offers a novel approach to tackling both infections simultaneously, which could simplify treatment regimens for patients co-infected with these viruses.

What evidence suggests that bepirovirsen might be an effective treatment for HIV and Hepatitis B?

Research has shown that bepirovirsen, which participants in this trial may receive, may help treat hepatitis B. Studies have found that it can lower the amount of a key virus marker, called hepatitis B surface antigen (HBsAg), in the blood. In some trials, 28-29% of patients had no detectable virus after 24 weeks of treatment. Additionally, 9-10% of participants experienced a significant drop in HBsAg and the virus's genetic material, indicating the treatment's potential effectiveness. While these results are promising for hepatitis B, its effects on people also infected with HIV remain under investigation. ^{1 2 3 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 people who have both HIV and chronic Hepatitis B. Specific details about eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to follow specific protocols related to their conditions.

Inclusion Criteria

Cluster of differentiation 4 (CD4) count >=350 cells/Cubic Millimeters (mm3)

Documented evidence of at least 2 plasma HIV-1 Ribonucleic acid (RNA) measurements <50 copies/mL are required in the 12 months prior to Screening: 1 within 6 to 12 months prior to screening and 1 within 6 months prior to Screening

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

Exclusion Criteria

I have taken interferon therapy in the last 12 months.

I can stop my blood thinner or anti-platelet medication safely for the study.

I have or might have liver cirrhosis or liver cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bepirovirsen or placebo for the study duration

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bepirovirsen

Trial Overview The study is testing the effectiveness and safety of a medication called bepirovirsen compared to a placebo in individuals with both HIV and chronic Hepatitis B virus infection.

How Is the Trial Designed?

Group I: Participants receiving Bepirovirsen Experimental Treatment 1 Intervention

Participants will receive bepirovirsen.

Group II: Participants receiving Placebo Placebo Group 1 Intervention

Participants will receive placebo.

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]

Adefovir dipivoxil (ADV) combined with pegylated interferon (PEG-IFN) is safe and effective for treating hepatitis B virus (HBV) that is resistant to lamivudine in HIV-coinfected patients, as shown in a study of 17 patients over 48 weeks.

While the treatment led to significant decreases in HBV DNA and liver enzyme levels, it did not result in HBV seroconversion or affect the progression of HIV disease, indicating that while the treatment is effective, it may not provide long-term benefits after therapy ends.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adefovir dipivoxil plus pegylated interferon-alpha2a for the treatment of lamivudine-resistant hepatitis B virus infection in HIV-infected patients. Ingiliz, P., Valantin, MA., Thibault, V., et al.[2018]

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 3 trial involving 197 patients with chronic hepatitis B virus (HBV) infection, besifovir dipivoxil maleate (BSV) demonstrated antiviral efficacy comparable to tenofovir disoproxil fumarate (TDF) after 48 weeks, with 80.9% of BSV patients achieving a virologic response compared to 84.9% for TDF, confirming BSV's non-inferiority.

BSV showed a better safety profile than TDF, particularly regarding bone mineral density and renal function, with no significant differences in these outcomes observed between the two groups after 96 weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection. Ahn, SH., Kim, W., Jung, YK., et al.[2020]

In a real-world study of 209 patients with chronic hepatitis C, the combination therapy of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin achieved a remarkable sustained virologic response (SVR) rate of 99.0%, confirming its high efficacy seen in clinical trials.

While the treatment was generally well-tolerated, with most adverse events being mild, serious side effects occurred in 3.8% of patients, highlighting the importance of monitoring for potential complications, especially in those with liver cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness and safety of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C: AMBER study. Flisiak, R., Janczewska, E., Wawrzynowicz-Syczewska, M., 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]

Telbivudine, a selective inhibitor for hepatitis B virus (HBV), showed no inhibitory effects on HIV-1, even at high concentrations (up to 600 µM), indicating its potential safety for use in patients coinfected with both viruses.

This lack of interaction suggests that telbivudine could be a viable treatment option for HBV in patients who are also infected with HIV-1, without the risk of inducing resistance to HIV treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Telbivudine exhibits no inhibitory activity against HIV-1 clinical isolates in vitro. Lin, K., Karwowska, S., Lam, E., et al.[2021]

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 ... GSK has initiated two randomized, double-blind, placebo-controlled Phase 3 studies evaluating the safety and efficacy of bepirovirsen (formerly IONIS-HBV Rx).

4. eatg.org eatg.org/hiv-news/investigational-hepatitis-b-therapy-is-granted-fda-fast-track-status/

Investigational hepatitis B therapy is granted FDA fast-track ... In previous data reports, GSK said 28-29% of patients with chronic hepatitis B has achieved undetectable virus levels after 24 weeks of treatment with ...

5. 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 ...

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

Safety, tolerability and antiviral activity of the antisense ... A dose-dependent reduction from baseline in HBsAg was observed at day 29 (7 d after the last dose) in the bepirovirsen treatment arms.

7. ir.ionis.com ir.ionis.com/news-releases/news-release-details/ionis-announces-presentation-positive-phase-2b-data-chronic

Ionis announces presentation of positive Phase 2b data for ... The B-Clear Phase 2b study is investigating the efficacy and safety of 12- or 24-weeks treatment with bepirovirsen in people living with CHB on stable NA ...