Efficacy and safety of stapokibart in adolescents with moderate-to-severe atopic dermatitis: a multicenter, randomized, double-blind, placebo-controlled phase 3 trial

Background Moderate-to-severe atopic dermatitis (AD) imposes a significant burden on adolescents and their families, leading to a substantial reduction in quality of life, while treatment options remain limited. Stapokibart, a novel humanized monoclonal antibody targeting IL-4Rα, has been approved for the treatment of adults with moderate-to-severe AD in China. Objectives To evaluate the efficacy and safety of stapokibart in adolescents with moderate-to-severe AD. Methods In this randomized, double-blind, placebo-controlled phase 3 trial (NCT06277765), eligible patients were randomized (2:1) to stapokibart 300 mg (loading dose, 600 mg) or placebo for 18 weeks. Patients with a baseline weight ≥60 kg received subcutaneous stapokibart or placebo every two weeks (q2w), while those weighting 30 to <60 kg received treatment every three weeks (q3w). All patients were given moisturizers during the whole study. Coprimary endpoints were proportions of patients achieving a ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75) and an Investigator's Global Assessment (IGA) score of 0/1 with ≥2-point reduction from baseline (IGA response) at week 18. The safety was also assessed. Results Of the 180 enrolled patients, 120 received stapokibart (54 q2w; 66 q3w) and 60 received placebo (26 q2w; 34 q3w). Totally 178 (98.9%) patients completed the double-blind treatment. At week 18, higher proportions of stapokibart- vs. placebo-treated patients achieved EASI-75 (73.9% [88/119] vs. 43.3% [26/60]; difference [95%CI]: 30.5% [15.3%, 44.3%]; P<0.0001) and an IGA response (57.1% [68/119] vs. 25.0% [15/60]; difference [95%CI]: 31.8% [16.6%, 44.4%]; P<0.0001). The proportion of patients achieving ≥4-point reductions in weekly average of daily Peak Pruritus Numerical Rating Scale score was also significantly higher in stapokibart group than in placebo group (36.1% [43/119] vs. 15.0% [9/60]; difference [95%CI]: 21.1% [7.4%, 32.4%]; P=0.0037). The incidence of adverse events was similar between the stapokibart (62.5% [75/120]) and placebo (61.7% [37/60]) groups. No conjunctivitis was found. Conclusion Stapokibart demonstrated high efficacy and favorable safety in adolescents with moderate-to-severe AD.