Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Stapokibart in Healthy Volunteers and Adult Subjects with Atopic Dermatitis.

Abstract

Stapokibart, a novel humanized anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits the signaling of IL-4 and IL-13, which are key drivers of type2 inflammation in atopic dermatitis (AD). This study aimedto assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of stapokibart in a randomized, double-blind, placebo-controlled single ascending dose (SAD) study and a multiple ascending dose (MAD) study. The SAD study enrolled 33healthy male adults aged 18-65years at a single center. The MAD study enrolled 39 patients with moderate-to-severe AD aged 18-70years at seven centers. Enrolled subjects were randomized to subcutaneous (SC) doses of stapokibart (75-600mg) or placebo. Serum thymus and activation-regulated chemokine (TARC) and total immunoglobulinE (IgE) were measured as PD biomarkers for stapokibart. Similar PK characteristics were observed in healthy volunteers and subjects with AD after the initial administration. Stapokibart exhibited non-linear pharmacokinetics in both types of subjects. Following single doses, the mean maximum serum concentration (Cmax) ranged from 5.3 to 63.0μg/mL, median Tmax ranged from 3.0 to 7.0days, mean terminal half-life (t1/2z) ranged from 2.39 to 7.43days, and mean apparent volume (Vz/F) ranged from 3.64 to 6.73L in healthy subjects. The mean AUC accumulation ratio was 2.29 in subjects with AD after three doses of stapokibart 300mg administered every 2weeks. The median serum total IgE and TARC levels on day43 decreased from baseline by 14.9-25.2% and 48.6-77.0%, respectively, among subjects with AD receiving three doses of stapokibart. No subjects developed grade ≥ 3 adverse events (AEs) or serious AEs or discontinued the study because of AEs. The incidence of AEs was similar between stapokibart and placebo groups. Stapokibart showed favorable pharmacokinetics, pharmacodynamics, safety, and tolerability in the SAD and MAD studies. Based on these results, phaseII and phaseIII trials of stapokibart have been performed in subjects with moderate-to-severe AD. ClinicalTrials.gov Identifier NCT06161090 (29 November, 2023), NCT04893941 (15 May, 2021).