A Phase 1 Randomized Study: Garadacimab Pharmacokinetics, Safety, and Tolerability After Administration via Autoinjector/Pre‐Filled Pen Versus Pre‐Filled Syringe in Healthy Participants

Garadacimab is a novel, fully human, anti‐activated factor XII monoclonal antibody approved for long‐term prophylaxis of patients with hereditary angioedema. This open‐label, parallel‐group, Phase 1, single‐center, bridging study in healthy adults (18–55 years of age) characterized the pharmacokinetics and safety of a single 200 mg subcutaneous injection of garadacimab administered via autoinjector/pre‐filled pen (AI/PFP) compared with the pre‐filled syringe (PFS) used in previous studies. The aim of the study was to bridge the understanding of the PK and safety of garadacimab between PFS and AI/PFP modes of administration. Participants (N = 132) were stratified by body weight, randomized evenly in six groups by device (AI/PFP or PFS) and injection site (abdomen, thigh, or upper arm). The primary endpoint comprised pharmacokinetic parameter comparison between devices. Safety/tolerability were secondary endpoints. The geometric mean ratio (GMR) for C max and AUC 0–inf comparing administration by PFS and AI/PFP was close to 1 with 90% confidence intervals within a range of 0.8–1.25, meeting bioequivalence criteria; GMR (90%) was 0.92 (0.81, 1.05) for C max and 0.96 (0.87, 1.07) for AUC 0–inf . No participants in this study had anti‐drug antibodies against garadacimab. Treatment‐related emergent adverse events were reported in 9/66 (13.6%) participants in the PFS group and 11/66 (16.7%) participants in the AI/PFP group. Garadacimab 200 mg administered as a single subcutaneous dose via AI/PFP had a consistent safety and tolerability profile to that administered via PFS. These findings support administration of garadacimab via AI/PFP, providing at‐home convenience for patients and physicians.