Study to Evaluate the Effect of Bepirovirsen on Cardiac Conduction as Assessed by 12-lead Electrocardiogram in Healthy Volunteers

A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Parallel Group Study to Evaluate the Effect of Bepirovirsen on Cardiac Conduction as Assessed by 12-lead Electrocardiogram in Healthy Volunteers

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. The data generated will be used to model the relationship between bepirovirsen concentration and QTcF.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: Bepirovirsen; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744 -1645
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
• Participants who are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, electrocardiogram (ECG) and vital signs.
• Body weight greater than equal to (>=) 50 Kilograms (kg) and Body mass index (BMI) within the range 19-32 Kilograms per square meter (kg/m^2) (inclusive).

• Study will enroll both male and female participants.

  o Female participants are eligible to participate if they are not pregnant or breastfeeding and are either not of childbearing potential or agree to using a highly effective method of contraception.

• Capable of giving signed informed consent.

Exclusion Criteria:

• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
• History of vasculitis or presence of symptoms and signs of potential vasculitis
• History of lymphoma, leukemia, or any malignancy except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for at least 3 years.
• Participants with any other medical conditions which, in the judgement of the investigator and/or Medical Monitor, could jeopardize the integrity of the data derived from that participant or the safety of the participant.
• Past, current or intended use of over-the-counter or prescription medication, including herbal medications within 7 days or 5 half-lives (whichever is longer) before dosing.
• Current or recent use of creatine-containing supplements, or intended use up to 50 days post-dosing.
• Prior treatment with any oligonucleotide or small interfering Ribonucleic acid (RNA) (siRNA) within 12 months before dosing.
• Exposure to more than 4 new chemical entities within 12 months before the first dosing day
• Current enrollment or past participation in another investigational study in which an investigational intervention (e.g., drug, vaccine, invasive device) was administered within 5 half-lives (if known) or twice the duration of biological effect (if known), whichever is longer, or within the last 90 days (if half-life and duration of biological effect are unknown), before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research.
• Current enrollment or past participation in this clinical study.
• Positive pre-clinical drug/alcohol screen, including tetrahydrocannabinol.
• Positive Human Immunodeficiency Virus antibody test.
• History or regular use of tobacco or nicotine-containing products within 6 months prior to screening.
• Regular alcohol consumption within 6 months prior to screening defined as an average weekly intake of >14 units for males or females.
• Regular use of known drugs of abuse, including tetrahydrocannabinol.
• Sensitivity to heparin or history of heparin-induced thrombocytopenia.
• History of sensitivity to bepirovirsen or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor contraindicates their participation.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Positive test results for Hepatitis B surface antigen (HBsAg), hepatitis C antibody or hepatitis C RNA at screening or within 3 months prior to first dose of study intervention.
• Known history of heart disease, including ischemic heart disease, cardiomyopathy, clinically significant cardiac arrhythmias, clinically significant valvular disease, or hypertensive heart disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bepirovirsen: Four-Dose SC Injection; Participant received four subcutaneous (SC) injections of Bepirovirsen dose level 1 on Day 1.	Drug: Bepirovirsen; Bepirovirsen was administered.
Placebo Comparator: Placebo: Four SC Injections; Participants received four matching placebo SC injections on Day 1.	Drug: Placebo; Placebo was administered.
Active Comparator: Bepirovirsen: Three-Dose SC Injection; Participant received three SC injections of Bepirovirsen dose level 1 on Day 1.	Drug: Bepirovirsen; Bepirovirsen was administered.
Placebo Comparator: Placebo: Three SC Injections; Participants received three matching placebo SC injections on Day 1.	Drug: Placebo; Placebo was administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placebo-corrected Change From Baseline (CFB) in QT Interval Corrected by Fridericia's Formula (QTcF) Following Administration of Bepirovirsen Supratherapeutic Single Dose	Continuous 12-lead electrocardiogram (ECG) was captured by Holter monitor. QTcF was measured from 10 digital ECGs extracted from the continuous tracing after 10 minutes of rest in supine position. Baseline was defined as pre-dose value on Day 1. Change from Baseline (CFB) was calculated by subtracting post-dose visit value from Baseline value. Geometric mean and 90 percent (%) Confidence Interval (CI) of predicted CFB QTcF adjusted for placebo at Cmax following supratherapeutic single doses of Bepirovirsen was presented using concentration QTc (C-QTc) analysis using exposure-response modelling. This approach utilized pre-specified linear mixed effects model where CFB QTcF was dependent variable. Fixed-effect parameters included intercept, slope, influence of Baseline on intercept, treatment and nominal time from first dose. Participant was included as additive random effect on both intercept and slope terms.	Baseline (Pre-dose on Day 1) and Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in RR Interval in ECG at Indicated Timepoints	Twelve-lead ECGs were extracted from continuous Holter monitor tracings and RR interval was measured. RR interval is the time duration between the peak of one R wave and the peak of the very next R wave on the ECG. RR interval represents the time between two consecutive heartbeats. ECGs were extracted after a 10 minute supine rest period. Baseline was defined as pre-dose value on Day 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.	Baseline (Pre-dose on Day 1) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 27, 30, 33, 36, 48, 51, 54, 57, 60 and 72 hours post-dose
Change From Baseline in QTcF Interval, PR Interval and QRS Duration at Indicated Timepoints	Continuous 12-lead ECG was captured by Holter monitor. QTcF, PR interval and QRS duration were measured from 10 digital ECGs extracted from the continuous tracing after 10 minutes of rest in supine position. Baseline was defined as pre-dose value on Day 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.	Baseline (Pre-dose on Day 1) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 27, 30, 33, 36, 48, 51, 54, 57, 60 and 72 hours post-dose
Number of Participants With Outlier Results for Heart Rate (HR)	Continuous 12-lead ECG was captured by Holter monitor. HR was measured from 10 digital ECGs extracted from the continuous tracing after 10 minutes of rest in supine position. Participants with HR less than (<) 50 beats per minute (bpm) with a decrease of HR greater than (>) 25% and HR >100 bpm with an increase of HR >25% were considered as outlier.	Up to Day 4
Number of Participants With Outlier Results for Total QTcF Interval, PR Interval and QRS Duration	Twelve-lead ECG were obtained to measure QTcF interval, PR interval and QRS duration. 12-lead ECG were recorded in a participant using an ECG machine after 10 minutes rest in the supine position. Participants with outlier results were determined if the following criteria (which were assessed separately) were met: Participant who had treatment-emergent (TE) value of QTcF>450 and <=480 milliseconds (ms) when not present at Baseline (new onset); TE value of QTcF>480 and <=500 ms when not present at Baseline (new onset); TE value of QTcF>500 ms when not present at Baseline (new onset); increase of QTcF from Baseline of >30 and <=60 ms; increase of QTcF from baseline >60 ms; Increase in PR interval from Baseline >25% resulting in PR >200 ms; increase in QRS duration from Baseline >25% resulting in QRS >120 ms.	Up to Day 4
Number of Participants With Treatment Emergent Changes of T Wave Morphology and U-wave Presence	Twelve-lead ECG were obtained using an ECG machine. T-wave morphology was categorized as follows: Flat T wave: T amplitude <1 millimeter (mm) (either positive or negative) including flat isoelectric line. Notched T wave(+): Presence of notch(es) of at least 0.05 millivolt(mV) amplitude on ascending or descending arm of positive T wave. Biphasic: T wave that contains a second component with an opposite phase that is at least 0.1 mV deep (both positive/negative and negative/positive and polyphasic T waves included). T wave Inversion: T wave which normally points upward in most leads, is seen pointing downward (negative). Normal T wave(-): T amplitude that is negative, without biphasic T wave or notches. Notched T wave(-): Presence of notch(es) of at least 0.05 mV amplitude on descending or ascending arm of the negative T wave. U waves: Presence of abnormal U waves. Number of participants who had any treatment emergent changes of T wave morphology and U-wave presence have been presented.	Up to Day 4
Plasma Concentrations of Bepirovirsen	Blood samples were collected at the indicated time points for pharmacokinetic (PK) analysis of Bepirovirsen.	At 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 27, 30, 33, 36, 48, 51, 54, 57, 60 and 72 hours post-dose
Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Bepirovirsen	Blood samples were collected at the indicated time points for pharmacokinetic analysis of Bepirovirsen.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 27, 30, 33, 36, 48, 51, 54, 57, 60 and 72 hours post-dose
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC[0-24]) of Bepirovirsen	Blood samples were collected at the indicated time points for pharmacokinetic analysis of Bepirovirsen.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose
Maximum Plasma Concentration (Cmax) of Bepirovirsen	Blood samples were collected at the indicated time points for pharmacokinetic analysis of Bepirovirsen.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 27, 30, 33, 36, 48, 51, 54, 57, 60 and 72 hours post-dose
Time to Reach Cmax (Tmax) of Bepirovirsen	Blood samples were collected at the indicated time points for pharmacokinetic analysis of Bepirovirsen.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 27, 30, 33, 36, 48, 51, 54, 57, 60 and 72 hours post-dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC(0-t) of Bepirovirsen	Blood samples were collected at the indicated time points for pharmacokinetic analysis of Bepirovirsen.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 27, 30, 33, 36, 48, 51, 54, 57, 60 and 72 hours post-dose

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: PPD Development, LP
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2024
• Primary Completion (Actual): April 28, 2025
• Study Completion (Actual): April 28, 2025

Study Registration Dates

• First Submitted: May 15, 2024
• First Submitted That Met QC Criteria: May 15, 2024
• First Posted (Actual): May 21, 2024

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: June 13, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Electrocardiogram; Hepatitis B virus; Bepirovirsen; Cardiac Conduction; QT interval corrected by Fridericia's formula
• Additional Relevant MeSH Terms: Blood-Borne Infections; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis; Hepatitis B
• Other Study ID Numbers: 205873

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No