Open AccessTopical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double‐blind, placebo‐controlled Phase 2 trial
Author(s) -
Weiss Anne,
Delavenne Emilie,
Matias Carina,
Lagler Heimo,
Simon Daniel,
Li Ping,
Hansen Jon U.,
Santos Teresa Pires,
Jana Bimal,
Priemel Petra,
Bangert Christine,
Bauer Martin,
Eberl Sabine,
NussbaumerPröll Alina,
Anne Österreicher Zoe,
Matzneller Peter,
Quint Tamara,
Weber Maria,
Nielsen Hanne Mørck,
Rades Thomas,
Johansen Helle Krogh,
Westh Henrik,
Kim Wooseong,
Mylonakis Eleftherios,
Friis Christian,
Guardabassi Luca,
Pace John,
Lundberg Carina Vingsbo,
M'Zali Fatima,
Butty Pascal,
Sørensen Nikolaj,
Nielsen Henrik Bjørn,
ToftKehler Rasmus,
GuttmanYassky Emma,
Stingl Georg,
Zeitlinger Markus,
Sommer Morten
Publication year - 2022
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.790
Subject(s) - atopic dermatitis , staphylococcus aureus , medicine , microbiome , placebo , randomized controlled trial , colonization , psoriasis , skin infection , dermatology , immunology , microbiology and biotechnology , biology , bioinformatics , pathology , bacteria , genetics , alternative medicine
Abstract Background In patients with atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions and is hypothesized to be linked to disease severity and progression. Treatments that reduce S. aureus colonization without significantly affecting the skin commensal microbiota are needed. Methods and findings In this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce S. aureus and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double‐blind and placebo‐controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on S. aureus colonization and skin microbiome composition in patients with mild‐to‐severe AD (EudraCT:2016‐003501‐33). ATx201 has a narrow minimal inhibitory concentration distribution (.125–.5 μg/ml) consistent with its mode of action – targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin‐resistant S. aureus . In a Phase 2 trial in patients with mild‐to‐severe AD ( N = 36), twice‐daily treatment with ATx201 OINTMENT 2% effectively reduces S. aureus colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, p = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle. Conclusion These results suggest that ATx201 could become a new treatment modality as a decolonizing agent.