A Phase 1, Randomized, Open-Label, Parallel Group Study to Evaluate the Relative Bioavailability and Safety of...

Bepirovirsen, an antisense oligonucleotide in development for the treatment of chronic hepatitis B virus (HBV) infection, is administered from glass vials as a subcutaneous (SC) injection by healthcare professionals (HCPs). A ready-to-use prefilled syringe (PFS) assembled with a safety syringe device (SSD) has been developed to make administration more convenient and facilitate patient self-administration. This Phase 1, open-label, randomized, parallel-group study evaluated the relative bioavailability of bepirovirsen delivered from a vial or PFS SSD, assessed the viability of PFS SSD self-administration, and evaluated the safety and tolerability of SC bepirovirsen in healthy participants. Participants (N = 159) received a single 300 mg SC dose of bepirovirsen administered by a HCP (vial [n = 46] or PFS SSD [n = 49]), or self-administered (PFS SSD, with [n = 32] or without [n = 32] training from a HCP). Relative bioavailability (primary endpoint) of HCP-administered bepirovirsen delivered by vial versus PFS SSD was assessed using maximum observed plasma concentration (C_max) and area under the concentration-time curve from time zero extrapolated to infinity (AUC_(0-inf)). Participants were monitored for adverse events. Bepirovirsen exposure was bioequivalent when HCP-administered either by vial or PFS SSD; the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) were within the standard bioequivalence reference range, 0.80-1.25, for both C_max (1.02 [0.91-1.14]) and AUC_(0-inf) (1.05 [0.96-1.15]). Self-administration using PFS SSD achieved bioequivalence for bepirovirsen exposure compared with HCP administration. No new safety concerns were identified. These findings confirm that PFS SSD is a viable alternative to vials for bepirovirsen administration, when HCP- or self-administered, for the treatment of chronic HBV. Clinical trial identifier: NCT06058390.