Comparable pharmacokinetics (PK), safety and tolerability of astegolimab administered subcutaneously (SC) via abdomen, thigh or upper arm: a Phase I, single-dose study

<bold>Rationale:</bold> Astegolimab, a human IgG2 monoclonal antibody that inhibits ST2 (the interleukin [IL]-33 receptor), is under development for COPD. Astegolimab was administered SC to the abdomen (AB) in COPD clinical trials. Alternative injection sites may be clinically convenient. We evaluated the effect of injection site on astegolimab PK, safety and immunogenicity. <bold>Methods:</bold> In this open-label study (<ext-link>NCT06462118</ext-link>), healthy adults (18–55 years; BMI: 18–30 kg/m²) were randomised 1:1:1 to a single-dose SC astegolimab in the AB, thigh (TH) or upper arm (UA). <bold>Results:</bold> 78 participants received astegolimab in the AB, TH or UA (n=26 each). Figure shows concentration–time profiles. Geometric mean ratios and 90% CIs of all primary PK parameters were fully contained within the predefined limits (70–143%; reference: AB) and bioequivalence criteria (80–125%) suggesting PK exposure for TH and UA were comparable to AB. Treatment-related adverse events (AEs) were Grade 1 (headache, n=3; nasal congestion, n=1) or 1–2 (injection site reactions, n=22; resolved without medication). No serious/Grade ≥3 AEs occurred. Incidence of antidrug antibodies was 2.6%. <bold>Conclusion:</bold> PK of single-dose astegolimab in UA or TH are comparable to AB, with reassuring immunogenicity, safety and tolerability, supporting the use of alternative injection sites for astegolimab administration. <fig><object-id>erj;66/suppl_69/OA2341/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>