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

Abstract

BACKGROUND:

The 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.

OBJECTIVES:

This study sought to assess the efficacy, safety, and pharmacokinetics of astegolimab in patients with atopic dermatitis.

METHODS:

This 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.

RESULTS:

A 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.

CONCLUSIONS:

In patients with atopic dermatitis, astegolimab did not show a significant difference compared to placebo for the primary or secondary outcomes.

• Authors: Marcus Maurer, Dorothy S Cheung, Wiebke Theess, Xiaoying Yang, Michael Dolton, Anna Guttman, David F Choy, Ajit Dash, Michele A Grimbaldeston, Weily Soong
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 150 Issue 6 Pg. 1517-1524 (12 2022) ISSN: 1097-6825 [Electronic] United States
• PMID: 36041655 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-33
• astegolimab
• Antibodies, Monoclonal, Humanized

Topics

• Humans
• Dermatitis, Atopic (drug therapy)
• Interleukin-33
• Antibodies, Monoclonal, Humanized (therapeutic use)