Phase 2 randomized clinical trial of astegolimab in patients with moderate to severe atopic dermatitis

BackgroundThe binding of IL-33 to its receptor ST2 (alias of IL1RL1) leads to the release of inflammatory mediators and may play a role in the pathogenesis of atopic dermatitis. Astegolimab is a fully human, IgG2 mAb that binds to ST2 and inhibits IL-33 signaling.ObjectivesThis study sought to assess the efficacy, safety, and pharmacokinetics of astegolimab in patients with atopic dermatitis.MethodsThis was a randomized, placebo-controlled, phase 2 study in which adults with chronic atopic dermatitis were randomized 1:1 to receive astegolimab 490 mg every 4 weeks or placebo, for 16 weeks. The primary outcome was the percentage of change from baseline to week 16 of the Eczema Area and Severity Index score.ResultsA total of 65 patients were enrolled in the study (placebo, n = 32; astegolimab, n = 33). The adjusted mean percentage of change from baseline to week 16 in the Eczema Area and Severity Index score was −51.47% for astegolimab compared with −58.24% for placebo, with a nonsignificant treatment difference of 6.77% (95% CI: −16.57-30.11; P = .5624). No differences were observed between treatment groups for secondary efficacy outcomes and in exploratory biomarkers (blood eosinophils, serum IL-5, serum CCL13). With the use of loading dose, pharmacokinetic exposure was sufficient from week 1. Astegolimab was well-tolerated, with a safety profile consistent with that observed in previous clinical trials.ConclusionsIn patients with atopic dermatitis, astegolimab did not show a significant difference compared to placebo for the primary or secondary outcomes.