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

Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06422767
• Other study ID #: 205873
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 3, 2024
• Est. completion date: October 8, 2024

Study information

• Verified date: May 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: October 8, 2024
• Est. primary completion date: September 20, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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 (ECGs) 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).

• Male Participants: There are no contraceptive requirements for male participants.

• A female participant is eligible to participate:

• if she is not pregnant or breastfeeding and 1 of the following conditions applies:

1. is a woman of non-childbearing potential (WONCBP). OR

2. is a WOCBP and using a contraceptive method.

• 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

• A sustained supine systolic blood pressure greater than (>)150 millimeters of mercury (mmHg) or less than (<)90 mmHg or a supine diastolic blood pressure >95 mmHg or <50 mmHg at Screening or Check-in (Day -2).

• 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 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.

• Platelets <140 x 10^9 cells/liter (L).

• Serum calcium, magnesium or potassium levels outside the normal reference range at screening.

• 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 prior 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 prior to 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 (tetrahydrocannabinol).

• Positive Human Immunodeficiency Virus antibody test.

• Cotinine levels indicative of smoking or 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.

• Alanine aminotransaminase (ALT) >1.5x Upper Limit of Normal (ULN).

• Total bilirubin >1.5xULN; Participants with Gilbert's syndrome can be included with total bilirubin >1.5x ULN as long as direct bilirubin is less than equal to (<=) 1.5xULN.

• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

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

• Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.

• Positive hepatitis C RNA test result 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.

1. History of palpitations associated with presyncope or syncope, or history of unexplained syncope.

2. History of Brugada syndrome, ventricular pre-excitation syndromes, personal or family history of long QT syndrome, or family history of sudden cardiac death.

• Exclusion criteria for Screening ECG:

1. A supine mean heart rate outside the range 50 to 100 beats per minute (bpm). A HR from 100 to 110 bpm can be rechecked by ECG or vital signs within 2 hours to verify eligibility.

2. QT interval corrected by Fridericia's formula (QTcF) >450 milliseconds (msec).

3. QRS interval >120 msec

4. PR interval >210 msec

5. An uninterpretable ECG or any significant arrhythmia or conduction abnormality which, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, will interfere with the safety of the individual participant.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis B

Intervention

Drug:
• Bepirovirsen
Bepirovirsen will be administered.
• Placebo
Placebo will be administered.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Austin	Texas

Sponsors (3)

Lead Sponsor	Collaborator
GlaxoSmithKline	Laboratory Corporation of America, PPD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in QT interval corrected by Fridericia's formula (QTcF)		Baseline (Day 1) and up to Day 4
Secondary	Change from Baseline in heart rate (HR) using by-time point analysis		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
Secondary	Change from Baseline in QT interval, corrected by Fridericia's formula (QTcF), using by-time point analysis		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
Secondary	Change from Baseline in PR interval using by-time point analysis		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
Secondary	Change from Baseline in QRS duration using by-time point analysis		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
Secondary	Number of participants with outlier results for QT interval, corrected by Fridericia's formula (QTcF), HR, PR and QRS		Up to Day 4
Secondary	Number of participants with treatment emergent changes of T wave morphology and U-wave presence		Up to Day 4
Secondary	Plasma concentrations of Bepirovirsen		Up to Day 4
Secondary	Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) of Bepirovirsen		Up to Day 4
Secondary	Area under the concentration-time curve from time zero (pre-dose) to 24 hours post-dose (AUC[0-24]) of Bepirovirsen		Up to 24 hours
Secondary	Maximum concentration (Cmax) of Bepirovirsen in plasma		Up to Day 4
Secondary	Time to reach Cmax (Tmax) of Bepirovirsen		Up to Day 4