## Protocol Section
### Identification Module
**NCT ID:** NCT06422767

**Brief Title:** 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

#### Organization Study ID Info
**ID:** 205873
#### Organization
**Class:** INDUSTRY
**Full Name:** GlaxoSmithKline
### Status Module
#### Completion Date
**Date:** 2024-10-08

**Type:** ESTIMATED

#### Last Update Post Date
**Date:** 2024-05-21

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-15

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-09-20

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-03

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-21
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-15
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** PPD

**Class:** INDUSTRY

**Name:** Laboratory Corporation of America

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** GlaxoSmithKline

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** False

### Description Module

**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 Module

**Conditions:**

- Hepatitis B

**Keywords:**

- Bepirovirsen

- Cardiac Conduction

- Electrocardiogram

- QT interval corrected by Fridericia's formula

- Hepatitis B virus

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** DOUBLE

**Masking Description:** This will be a double-blind study.

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 100

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: Bepirovirsen

**Label:** Participants receiving Bepirovirsen

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: Placebo

**Label:** Participants receiving Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Participants receiving Bepirovirsen

**Description:** Bepirovirsen will be administered.

**Name:** Bepirovirsen

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Participants receiving Placebo

**Description:** Placebo will be administered.

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Change from Baseline in QT interval corrected by Fridericia's formula (QTcF)

**Time Frame:** Baseline (Day 1) and up to Day 4

#### Secondary Outcomes

**Measure:** Change from Baseline in heart rate (HR) using by-time point analysis

**Time Frame:** 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

**Time Frame:** 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

**Time Frame:** 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

**Time Frame:** 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

**Time Frame:** Up to Day 4

**Measure:** Number of participants with treatment emergent changes of T wave morphology and U-wave presence

**Time Frame:** Up to Day 4

**Measure:** Plasma concentrations of Bepirovirsen

**Time Frame:** 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

**Time Frame:** 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

**Time Frame:** Up to 24 hours

**Measure:** Maximum concentration (Cmax) of Bepirovirsen in plasma

**Time Frame:** Up to Day 4

**Measure:** Time to reach Cmax (Tmax) of Bepirovirsen

**Time Frame:** Up to Day 4

### Eligibility Module

**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 (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.

**Healthy Volunteers:** True

**Maximum Age:** 55 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** GSKClinicalSupportHD@gsk.com

**Name:** US GSK Clinical Trials Call Center

**Phone:** 877-379-3718

**Role:** CONTACT

**Contact 2:**

**Email:** GSKClinicalSupportHD@gsk.com

**Name:** EU GSK Clinical Trials Call Center

**Phone:** +44 (0) 20 89904466

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Austin

**Contacts:**

***Contact 1:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** US GSK Clinical Trials Call Center

- **Phone:** 877-379-3718

- **Role:** CONTACT

***Contact 2:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** EU GSK Clinical Trials Call Centre

- **Phone:** +44 (0) 20 8990 4466

- **Role:** CONTACT

***Contact 3:***

- **Name:** Brian Spears

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** GSK Investigational Site

**State:** Texas

**Zip:** 78744

### IPD Sharing Statement Module

**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.

**Description:** Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

- CSR

**IPD Sharing:** YES

**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.

**URL:** https://www.gsk.com/en-gb/innovation/trials/data-transparency/

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000008107

- Term: Liver Diseases

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000006525

- Term: Hepatitis, Viral, Human

- ID: D000014777

- Term: Virus Diseases

- ID: D000007239

- Term: Infections

- ID: D000086982

- Term: Blood-Borne Infections

- ID: D000003141

- Term: Communicable Diseases

- ID: D000018347

- Term: Hepadnaviridae Infections

- ID: D000004266

- Term: DNA Virus Infections

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M9592

- Name: Hepatitis A

- Relevance: LOW

- As Found: Unknown

- ID: M9591

- Name: Hepatitis

- Relevance: HIGH

- As Found: Hepatitis

- ID: M9595

- Name: Hepatitis B

- Relevance: HIGH

- As Found: Hepatitis B

- ID: M17522

- Name: Virus Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11107

- Name: Liver Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9610

- Name: Hepatitis, Viral, Human

- Relevance: LOW

- As Found: Unknown

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2593

- Name: Blood-Borne Infections

- Relevance: LOW

- As Found: Unknown

- ID: M20487

- Name: Hepadnaviridae Infections

- Relevance: LOW

- As Found: Unknown

- ID: M7442

- Name: DNA Virus Infections

- Relevance: LOW

- As Found: Unknown

- ID: T2787

- Name: Herpes Simiae (B Virus)

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006509

- Term: Hepatitis B

- ID: D000006505

- Term: Hepatitis

### Misc Info Module

- Version Holder: 2024-05-31
