The following is a summary of “Clinical and molecular effects of oral CCR4 antagonist RPT193 in atopic dermatitis: A Phase 1 study,” published in the November 2023 issue of Allergy & Immunology by Bissonnette, et al.

RPT193 is a small-molecule antagonist of the human C-C motif chemokine receptor 4 (CCR4) that can be administered orally. It inhibits the migration and downstream activation of T-helper Type 2 (Th2) cells. For a study, researchers sought to investigate single and multiple ascending doses of RPT193 in healthy individuals and multiple doses in individuals with moderate-to-severe atopic dermatitis (AD).

This Phase 1a/1b study was randomized and placebo-controlled. It focused on monotherapy to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 surface receptor occupancy in eligible healthy participants and those with moderate-to-severe AD. Additionally, clinical efficacy and skin biomarker effects of RPT193 monotherapy were explored in AD participants.

In both healthy (n = 72) and AD subjects (n = 31), once-daily RPT193 treatment was generally well tolerated, with no serious adverse events reported, and all treatment-emergent adverse events were mild/moderate. Notably, in AD subjects, RPT193 monotherapy showed numerically greater improvements in clinical efficacy endpoints compared to placebo up to the end of the treatment period (Day 29). Furthermore, a statistically significant improvement compared to Day 29 and placebo was observed 2 weeks after the end of treatment (Day 43) on several endpoints (P < .05). Significant changes in the transcriptional profile were also observed in skin biopsies of RPT193-treated versus placebo-treated subjects at Day 29, which were significantly correlated with improvements in clinical efficacy measures.

This study represented the first clinical investigation with an oral CCR4 antagonist demonstrating clinical improvement alongside modulation of the cutaneous transcriptomic profile in inflammatory skin disease.

Reference: onlinelibrary.wiley.com/doi/10.1111/all.15949