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

Abstract 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