A Study to Evaluate the Relative Bioavailability of Subcutaneous Bepirovirsen When Delivered From a Vial or Prefilled Syringe Fitted With a Safety Syringe Device in Healthy Adult Participants

NCT06058390 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 219239
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, randomized study to investigate subcutaneous (SC) bepirovirsen when delivered via SC injection from vial or Prefilled syringe fitted with a Safety syringe device (PFS SSD) in healthy adult participants. The aim of this study is to provide relative bioavailability data to support the transition from the vial presentation of bepirovirsen, to a ready-to-use liquid in a PFS SSD when both are given by a health care professional. The study will also assess self-administration using the PFS SDD, and the safety and tolerability of bepirovirsen.

Conditions

Hepatitis B

Keywords

Hepatitis B; Hepatitis; Viral; Human; Virus Diseases; Bepirovirsen; GSK3228836; 219239; Liver Diseases

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax) Following Administration of Bepirovirsen Using Vial and PFS by HCP

  Blood samples were collected at indicated timepoints for pharmacokinetic analysis of Bepirovirsen. Cmax calculation for this outcome measure is based on changes in model specifications and inclusion of different arms for respective outcome measures. Model includes Randomized Groups (Groups compared), injection site (arm, thigh and abdomen) as categorical covariates and log transformed Baseline weight as continuous covariate. The treatment is a factor in the model and position of a treatment as either test or reference would affect the Cmax values for a particular outcome measure due to differences in how the model accounts for variability and compares group for mean calculation. Pharmacokinetic (PK) Parameter Population included all participants in the PK concentration Population for whom valid and evaluable plasma PK parameters were derived.

  Pre-dose (Day 1) and Post-dose (1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours, 672 hours, 1008 hours and 1512 hours)

• Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC [0-Inf]) Following Administration of Bepirovirsen Using Vial and PFS by HCP

  Blood samples were collected at indicated timepoints for pharmacokinetic analysis of Bepirovirsen. Blood samples were collected at indicated timepoints for PK analysis of Bepirovirsen. AUC(0-inf) calculation for this outcome measure is based on changes in model specifications and inclusion of different arms for respective outcome measures. Model includes Randomized Groups (Groups compared), injection site (arm, thigh and abdomen) as categorical covariates and log transformed Baseline weight as continuous covariate. The treatment is a factor in the model and position of a treatment as either test or reference would affect the AUC(0-inf) values for a particular outcome measure due to differences in how the model accounts for variability and compares group for mean calculation.

  Pre-dose (Day 1) and Post-dose (1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours, 672 hours, 1008 hours and 1512 hours)

Secondary Outcomes (4)

• Maximum Observed Plasma Concentration (Cmax) Following Administration of Bepirovirsen Using PFS SSD by HCP and PFS SSD Self-administered Post-training

  Pre-dose (Day 1) and Post-dose (1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours, 672 hours, 1008 hours and 1512 hours)

• AUC(0-inf) Following Administration of Bepirovirsen Using PFS SSD by HCP and PFS SSD Self-administered Post-training

  Pre-dose (Day 1) and Post-dose (1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours, 672 hours, 1008 hours and 1512 hours)

• Maximum Observed Plasma Concentration (Cmax) Following Administration of Bepirovirsen Using PFS SSD by HCP and PFS SSD Self-administered Without Training

  Pre-dose (Day 1) and Post-dose (1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours, 672 hours, 1008 hours and 1512 hours)

• AUC(0-Inf) Following Administration of Bepirovirsen Using PFS SSD by HCP and PFS SSD Self-administered Without Training

  Pre-dose (Day 1) and Post-dose (1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours, 672 hours, 1008 hours and 1512 hours)

Study Arms (4)

Bepirovirsen Vial by HCP

EXPERIMENTAL

Participants will receive Bepirovirsen vial administered by Healthcare Professionals (HCP).

Drug: Bepirovirsen

Bepirovirsen PFS SSD by HCP

EXPERIMENTAL

Participants will receive Bepirovirsen PFS SSD administered by HCP.

Drug: Bepirovirsen

Bepirovirsen PFS SSD self-administered post-training

EXPERIMENTAL

Participants will receive Bepirovirsen PFS SSD self- administered with training by HCP.

Drug: Bepirovirsen

Bepirovirsen PFS SSD self-administered without training

EXPERIMENTAL

Participants will receive Bepirovirsen PFS SSD self- administered with no training by HCP.

Drug: Bepirovirsen

Interventions

Bepirovirsen DRUG

Bepirovirsen will be administered.

Bepirovirsen PFS SSD by HCP; Bepirovirsen PFS SSD self-administered post-training; Bepirovirsen PFS SSD self-administered without training; Bepirovirsen Vial by HCP

Eligibility Criteria

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

You may qualify if:

• Healthy participants as determined by medical evaluation including medical history, physical examination, laboratory tests, electrocardiogram (ECGs) and vital signs.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and protocol.

You may not qualify if:

• Past or current medical conditions which, in the judgement of the investigator and Medical Monitor, could jeopardize the integrity of the data derived from that participant or the safety of the participant.
• Abnormal blood pressure as determined by the investigator.
• Positive Hepatitis B virus (HBV), Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) test results.
• Participants with signs or symptoms suggestive of Coronavirus disease 2019 (COVID-19) within 14 days of inpatient admission, or with a positive test for active COVID-19 infection before study start.
• Past, current or intended use of over the counter or prescription medication \[including herbal medications\]
• Current or prior use of creatine-containing supplements and intended use up to 50 days post-dosing.
• Prior use of immunosuppressive drugs within 3 months before dosing or interferon within 12 months before dosing.
• Prior treatment with any oligonucleotide or small interfering ribonucleoside (RNA) siRNA within 12 months before dosing.
• Loss of blood or blood products in excess of 500 millilitre (mL) within any 3-month period during the study.
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• Current enrolment 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 the first dosing day in the current study.
• Current enrolment or past participation in this clinical study.
• 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 of alcohol within 6 months prior to the study.
• Regular use of known drugs of abuse, including Tetrahydrocannabinol (THC).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Las Vegas, Nevada, 89113, United States

Location

GSK Investigational Site

Austin, Texas, 78744, United States

Location

Related Publications (1)

• Youssef AS, Shah P, Hu M, Plein H, Roy A, Sharma R, Mole S, Blazejczyk M, Cross W, Spears B, Pak S, Kaur R, Elston R, Theodore D, Hezareh M, Nader A. A Phase 1, Randomized, Open-Label, Parallel Group Study to Evaluate the Relative Bioavailability and Safety of Subcutaneous Bepirovirsen when Delivered from a Vial or Prefilled Syringe Fitted with a Safety Syringe Device in Healthy Adult Participants. Clin Pharmacol Drug Dev. 2025 Oct 14. doi: 10.1002/cpdd.1615. Online ahead of print.

  PMID: 41085094 DERIVED

MeSH Terms

Conditions

Hepatitis B; Hepatitis; Virus Diseases; Liver Diseases

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Viral, Human; 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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: September 28, 2023
• Study Start: October 4, 2023
• Primary Completion: May 3, 2024
• Study Completion: May 3, 2024
• Last Updated: July 18, 2025
• Results First Posted: July 18, 2025

Record last verified: 2025-06

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 (2)