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

NCT06422767 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 205873
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatitis B

Keywords

Bepirovirsen; Cardiac Conduction; Electrocardiogram; QT interval corrected by Fridericia's formula; Hepatitis B virus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Change From Baseline in RR Interval in ECG at Indicated Timepoints

  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

  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)

  Up to Day 4

• Number of Participants With Outlier Results for Total QTcF Interval, PR Interval and QRS Duration

  Up to Day 4

• Number of Participants With Treatment Emergent Changes of T Wave Morphology and U-wave Presence

  Up to Day 4

Other Outcomes (1)

• AUC(0-t) 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

Study Arms (4)

Bepirovirsen: Four-Dose SC Injection

ACTIVE COMPARATOR

Participant received four subcutaneous (SC) injections of Bepirovirsen dose level 1 on Day 1.

Drug: Bepirovirsen

Placebo: Four SC Injections

PLACEBO COMPARATOR

Participants received four matching placebo SC injections on Day 1.

Drug: Placebo

Bepirovirsen: Three-Dose SC Injection

ACTIVE COMPARATOR

Participant received three SC injections of Bepirovirsen dose level 1 on Day 1.

Drug: Bepirovirsen

Placebo: Three SC Injections

PLACEBO COMPARATOR

Participants received three matching placebo SC injections on Day 1.

Drug: Placebo

Interventions

Bepirovirsen DRUG

Bepirovirsen was administered.

Bepirovirsen: Four-Dose SC Injection; Bepirovirsen: Three-Dose SC Injection

Placebo DRUG

Placebo was administered.

Placebo: Four SC Injections; Placebo: Three SC Injections

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• PPD Development, LP: collaborator

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744 -1645, United States

Location

MeSH Terms

Conditions

Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be a double-blind study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2024
• First Posted: May 21, 2024
• Study Start: July 18, 2024
• Primary Completion: April 28, 2025
• Study Completion: April 28, 2025
• Last Updated: July 10, 2026
• Results First Posted: July 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

US (1)