S. aureus colonization and clinical symptoms remain stable upon topical XZ.700 treatment: Results of a double-blind randomized clinical trial in patients with mild to moderate atopic dermatitis

Abstract

Aim: Recovering dysbiosis may improve atopic dermatitis (AD) symptoms. XZ.700 is a recombinant chimeric endolysin that specifically targets Staphylococcus aureus and could be a new treatment option for patients with AD. The aim of this first-in-human study was to evaluate the safety, tolerability and efficacy of topical XZ.700 and explore the pharmacodynamic effects in patients with mild to moderate AD.

Method and materials: This study consisted of Part A and Part B. In Part A, subjects were randomized and received XZ.700 10 μg/g, XZ.700 30 μg/g, XZ.700 100 μg/g or vehicle twice daily for 7 days on nonlesional skin and on all lesions (1% ≤ BSA ≤ 10%). In Part B, subjects received XZ.700 100 μg/g or vehicle on all lesions twice daily for 14 days (1% ≤ BSA ≤ 15%). Clinical scores and patient-reported outcomes were recorded. Pharmacodynamic measurements were taken.

Results: In total, 35 patients completed the study. Tolerability of XZ.700 was acceptable. XZ.700 100 μg/g showed no evidence of effect on cultured S. aureus (estimated difference -52.9% CFU/mL; 95% CI -88.4% to 90.8%), oSCORAD (1.03; 95% CI -5.20 to 7.26) or EASI (-0.534; 95% CI -2.48 to 1.41). Furthermore, XZ.700 treatment did not result in a significant reduction in the relative abundance of S. aureus via metagenomics or other pharmacodynamic outcomes.

Conclusion: Tolerability and safety of short-term topical administration of XZ.700 100 μg/g for 14 days were acceptable in most participants; however, some local application-site events occurred, and one hypersensitivity reaction led to discontinuation. XZ.700 did not demonstrate target engagement or clinical benefit vs. vehicle under the tested conditions.

Keywords: S. Aureus; atopic dermatitis; eczema; endolysin; microbiome.