An oral C-C motif chemokine receptor 4 (CCR4) antagonist, RPT193, has demonstrated promising results in an early-stage clinical trial for atopic dermatitis. The Phase 1 study (NCT04271514) evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 receptor occupancy of RPT193 in both healthy volunteers and individuals with moderate-to-severe atopic dermatitis.
The study, a randomized, placebo-controlled Phase 1a/1b monotherapy trial, enrolled 72 healthy subjects and 31 patients with moderate-to-severe atopic dermatitis. Participants received once-daily RPT193. The primary objective was to assess safety and tolerability, while exploratory endpoints included clinical efficacy and skin biomarker changes in atopic dermatitis subjects.
Safety and Tolerability
The trial indicated that RPT193 was generally well-tolerated. No serious adverse events were reported in either healthy subjects or atopic dermatitis patients. All treatment-emergent adverse events were reported as mild or moderate in severity.
Clinical Efficacy
Atopic dermatitis patients receiving RPT193 monotherapy exhibited numerically greater improvements in clinical efficacy endpoints compared to the placebo group by the end of the treatment period (Day 29). Notably, statistically significant improvements were observed two weeks after the treatment concluded (Day 43) across several endpoints (p < 0.05) when compared to both Day 29 results and the placebo group.
Biomarker Analysis
Skin biopsies from RPT193-treated subjects revealed significant changes in the transcriptional profile compared to those receiving placebo at Day 29. These transcriptional changes were significantly correlated with improvements observed in clinical efficacy measures, suggesting a potential mechanism of action for the drug.
The study suggests that RPT193 could offer a novel approach to treating atopic dermatitis by targeting CCR4 and modulating the immune response in the skin. Further studies are needed to confirm these findings and evaluate the long-term efficacy and safety of RPT193 in larger patient populations.
