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

GlaxoSmithKline160 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

160

Conditions

Hepatitis B

Interventions

Bepirovirsen

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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). * 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.

Outcomes

Primary Outcomes

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.

Time frame: 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.

Secondary Outcomes

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

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

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

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