Abstract
The chemokine receptor CCR4 mediates CCL17- and CCL22-driven chemotaxis of Th2 cells into the skin of patients with atopic dermatitis (AD). RPT193 is an oral CCR4 inhibitor that has been developed to treat AD and other allergic inflammatory diseases. The safety and efficacy of RPT193 as monotherapy for moderate-to-severe AD was previously described in a placebo-controlled, double-blinded Phase 1 study. Here, we present the skin and peripheral biomarker analysis from this Phase 1 trial. Following 28 days of 400 mg daily RPT193 treatment, RNA-seq and/or RT-PCR demonstrated significant downregulation of general inflammation- (MMP12; p<0.01), innate immunity- (IL8; p<0.01), T-cell/T-cell activation- (IL2, CCL19, CCR7, ICOS; p<0.05), Th1- (CCL2; p<0.05), Th2- (CCL22, CCR4; p<0.05), and Th17/Th22-related markers (IL22, CCL20, CCR6, S100A8, S100A9, S100A12, PI3/Elafin; p<0.05) compared to baseline in RPT193-treated, but not placebo-treated, subjects.
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