Clinical trial NCT06422767: Study to Evaluate the Effect of Bepirovirsen on Cardiac Conduction as Assessed by 12-lead Electrocardiogram in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis B
Keywords: Bepirovirsen
Cardiac Conduction
Electrocardiogram
QT interval corrected by Fridericia's formula
Hepatitis B virus
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
First posted: 2024-05-21
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in QT interval corrected by Fridericia's formula (QTcF)
timeFrame: Baseline (Day 1) and up to Day 4
Secondary outcomes:
measure: Change from Baseline in heart rate (HR) using by-time point analysis
timeFrame: Baseline (Day 1) and 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
measure: Change from Baseline in QT interval, corrected by Fridericia's formula (QTcF), using by-time point analysis
timeFrame: Baseline (Day 1) and 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
measure: Change from Baseline in PR interval using by-time point analysis
timeFrame: Baseline (Day 1) and 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
measure: Change from Baseline in QRS duration using by-time point analysis
timeFrame: Baseline (Day 1) and 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
measure: Number of participants with outlier results for QT interval, corrected by Fridericia's formula (QTcF), HR, PR and QRS
timeFrame: Up to Day 4
measure: Number of participants with treatment emergent changes of T wave morphology and U-wave presence
timeFrame: Up to Day 4
measure: Plasma concentrations of Bepirovirsen
timeFrame: Up to Day 4
measure: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) of Bepirovirsen
timeFrame: Up to Day 4
measure: Area under the concentration-time curve from time zero (pre-dose) to 24 hours post-dose (AUC[0-24]) of Bepirovirsen
timeFrame: Up to 24 hours
measure: Maximum concentration (Cmax) of Bepirovirsen in plasma
timeFrame: Up to Day 4
measure: Time to reach Cmax (Tmax) of Bepirovirsen
timeFrame: Up to Day 4
Other outcomes:
Locations:
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: