Bepirovirsen for HIV and Hepatitis B

(B-Focus Trial)

Recruiting at 46 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: GlaxoSmithKline

Must be taking: Antiretrovirals

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

Disqualifiers: Liver cirrhosis, Hepatocellular carcinoma, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study will evaluate the efficacy and safety of bepirovirsen compared to placebo in participants with human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection.

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.

What data supports the idea that Bepirovirsen for HIV and Hepatitis B is an effective drug?

The available research shows that Bepirovirsen is effective in reducing the levels of hepatitis B virus in the body. In a study, participants with chronic hepatitis B who were given Bepirovirsen experienced a significant reduction in the virus compared to those who received a placebo. Specifically, those who received a higher dose of 300 mg showed a notable decrease in the virus levels. This suggests that Bepirovirsen could be a promising option for treating hepatitis B, especially for those who have not responded well to other treatments. Additionally, Bepirovirsen was found to be safe, with most side effects being mild or moderate, such as reactions at the injection site. ^{1 2 3 4 5}

What safety data is available for Bepirovirsen in treating HIV and Hepatitis B?

Bepirovirsen has been evaluated in phase 2 trials for chronic Hepatitis B. The studies indicate that Bepirovirsen has a favorable safety profile, with most treatment-emergent adverse events being mild to moderate, such as injection site reactions. Transient, self-resolving alanine aminotransferase flares were observed in some participants. The safety data suggests that Bepirovirsen is generally well-tolerated, warranting further investigation in larger patient populations. ^{1 2 3 6 7}

Is the drug Bepirovirsen a promising treatment for HIV and Hepatitis B?

Yes, Bepirovirsen is a promising drug for treating Hepatitis B. It has shown the ability to significantly reduce the levels of the virus in the body, which is important for managing the disease. It also has a good safety profile, meaning it is generally safe for patients to use. ^{1 2 3 4 7}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

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

I have or might have liver cirrhosis or liver cancer.

I have or might have Hepatitis D.

Trial Timeline

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

Treatment Details

Interventions

• Bepirovirsen (Virus Therapy)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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. England 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. [2018]

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

Telbivudine exhibits no inhibitory activity against HIV-1 clinical isolates in vitro. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Real-world effectiveness and safety of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C: AMBER study. [2022]

7. United States 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. [2020]