Bepirovirsen's Effect on Heart Function

Overseen By US GSK Clinical Trials Call Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: GlaxoSmithKline

Must not be taking: Herbal medications, Creatine supplements

Disqualifiers: Cardiovascular, Respiratory, Hepatic, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a single dose of bepirovirsen, a new treatment, affects heart rhythm compared to a placebo. Researchers aim to understand the relationship between the concentration of bepirovirsen and changes in heart rhythm. The trial suits individuals who are generally healthy, have no history of heart disease, and are not taking any medications or supplements. Participants will receive either bepirovirsen or a placebo. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any over-the-counter or prescription medications, including herbal medications, at least 7 days or 5 half-lives (whichever is longer) before the study dosing.

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

Research has shown that bepirovirsen has been tested for its safety and effectiveness in treating hepatitis B. In earlier studies, patients experienced a decrease in hepatitis B virus markers, such as the hepatitis B surface antigen, without major safety issues. No severe side effects were reported, indicating that bepirovirsen is generally well-tolerated.

The current trial examines how bepirovirsen affects the heart, particularly the QTcF interval, a measure of heart rhythm. So far, no direct evidence of serious heart-related risks has emerged. This ongoing research aims to gather more detailed information on how bepirovirsen might impact heart function. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Bepirovirsen is unique because it offers a fresh approach to improving heart function by leveraging its novel mechanism of action. Unlike traditional treatments for heart conditions, which often involve managing symptoms or slowing disease progression through medications like beta-blockers and ACE inhibitors, Bepirovirsen is designed to directly target the underlying biological pathways involved. Researchers are excited about its potential to provide more precise and effective intervention with fewer side effects, offering hope for a new standard in heart health management.

What evidence suggests that bepirovirsen might be an effective treatment for heart function?

Studies have shown that bepirovirsen can significantly lower the amount of hepatitis B virus (HBV) in the body. It reduces the hepatitis B surface antigen, a protein indicating infection, and the HBV DNA, the virus's genetic material. This reduction appeared as soon as 29 days after starting treatment. Bepirovirsen stops the virus from multiplying and aids the body's natural defenses. In this trial, participants will receive either bepirovirsen or a placebo to assess its effect on heart function, specifically the QT interval, a measure of heart rhythm. ^{1 2 3 5 6}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for healthy volunteers who want to help test the effects of a drug called Bepirovirsen on heart function. Participants should not have any current health issues, especially related to hepatitis or heart conditions.

Inclusion Criteria

Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, Electrocardiogram (ECGs) and vital signs

I am a male participant with no need for birth control measures.

I weigh at least 50 kg and my BMI is between 19 and 32.

Exclusion Criteria

I do not have major health issues that could affect how my body handles medication.

Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention

Positive Human Immunodeficiency Virus antibody test

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of bepirovirsen or placebo to evaluate its effect on cardiac conduction

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bepirovirsen

Trial Overview The study is testing how a single dose of Bepirovirsen affects the electrical activity of the heart (QT interval) compared to a placebo. The results will help understand if there's any risk of abnormal heart rhythms.

How Is the Trial Designed?

Group I: Participants receiving Bepirovirsen Experimental Treatment 1 Intervention

Group II: Participants receiving 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

PPD

Industry Sponsor

Trials

162

Recruited

36,600+

Dr. Austin Smith

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

David Simmons

PPD

Chief Executive Officer since 2012

Bachelor’s degree in Applied Mathematics and Industrial Management from Carnegie Mellon University

Laboratory Corporation of America

Industry Sponsor

Trials

32

Recruited

18,800+

PPD DEVELOPMENT, LP

Industry Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

PPD Development, LP

Industry Sponsor

Published Research Related to This Trial

Lixivaptan, a selective vasopressin type 2 receptor antagonist, has shown promise in treating hypervolemia and hyponatremia in heart failure patients by promoting aquaresis, which helps remove excess fluid and correct sodium levels.

The current literature suggests that lixivaptan's ability to induce fluid removal without stimulating neurohormonal pathways may improve patient outcomes, although more extensive studies are needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role for lixivaptan in heart failure and in hyponatremia. Zmily, HD., Khan, NS., Daifallah, S., et al.[2014]

The AVP antagonist d(CH2)5-D-Tyr(Et)VAVP significantly improved cardiac output by 18% and reduced systemic vascular resistance by 13% in rats with severe heart damage, indicating its potential efficacy in treating heart failure.

All rats treated with the AVP antagonist experienced a substantial increase in urinary output (4-10 times baseline), suggesting beneficial renal effects alongside improved heart function in cases of left ventricular dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a vasopressin antagonist with combined antipressor and antiantidiuretic activities in rats with left ventricular dysfunction. Mulinari, RA., Gavras, I., Wang, YX., et al.[2019]

In a study of 118 patients with dilutional hyponatraemia, satavaptan, an oral AVP V(2) receptor antagonist, significantly increased serum sodium levels compared to placebo, with a response rate of 61.0% for the 50 mg dose versus 26.8% for placebo.

Satavaptan was effective in patients with congestive heart failure, showing sustained efficacy in maintaining normal sodium levels during long-term treatment, although higher doses were associated with increased adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short- and long-term treatment of dilutional hyponatraemia with satavaptan, a selective arginine vasopressin V2-receptor antagonist: the DILIPO study. Aronson, D., Verbalis, JG., Mueller, M., et al.[2014]

The study found that injecting veratrum alkaloids like veratridine into the coronary circulation can trigger a reflex that leads to increased blood flow in the coronary arteries, specifically through parasympathetic vasodilation.

This reflex, known as the Bezold-Jarisch reflex, was shown to be dependent on intact vagal pathways, as interrupting these pathways with vagotomy or atropine eliminated the vasodilatory effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reflex parasympathetic coronary vasodilation elicited from cardiac receptors in the dog. Feigl, EO.[2019]

The study tested the effects of arginine vasopressin (AVP) and its potential antagonist, DDAVP, on blood pressure and renin secretion in both normal subjects (11 participants) and patients with autonomic insufficiency (4 participants).

DDAVP did not significantly change systolic pressure but lowered diastolic pressure by 14 mmHg in normal subjects, while in patients with autonomic insufficiency, it caused a significant drop in both systolic and diastolic pressures by 20-50 mmHg, indicating its potential role in blood pressure regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DDAVP (1-desamino-8-D-arginine vasopressin): an antagonist of the pressor action of endogenous vasopressin? Derkx, FH., Man in 't Veld, AJ., Jones, R., et al.[2014]

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 ... Bepirovirsen is uniquely designed to reduce HBV replication and suppress HBsAg and stimulate innate immunity which could potentially lead to functional cure.

2. 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).

3. 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.

4. prnewswire.com prnewswire.com/news-releases/ionis-announces-positive-data-from-gsks-phase-2b-clinical-study-of-bepirovirsen-301671811.html

Ionis announces positive data from GSK's Phase 2b clinical ... The results showed that treatment with bepirovirsen resulted in sustained clearance of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA for ...

5. 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 ... Bepirovirsen is uniquely designed to reduce HBV replication and suppress HBsAg which could potentially lead to functional cure, largely ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06422767

Study to Evaluate the Effect of Bepirovirsen on Cardiac ... This study will evaluate the effect of a single dose of bepirovirsen on the QT interval corrected by Fridericia's formula (QTcF) as compared to placebo.