An oral C-C motif chemokine receptor 4 (CCR4) antagonist, RPT193, has shown promising results in a Phase 1 study involving adult patients with moderate to severe atopic dermatitis (AD). The study (NCT04271514) indicated that RPT193 led to greater improvements in clinical efficacy endpoints compared to a placebo, marking a potential advancement in AD treatment.
The trial, led by Bissonnette et al., aimed to assess the safety, tolerability, and efficacy of RPT193 in inhibiting the migration and activation of T-helper Type 2 (Th2) cells, which play a crucial role in AD pathogenesis. According to the study authors, this research is the first to demonstrate clinical improvement and modulation of the cutaneous transcriptomic profile in an inflammatory skin disease using a CCR4 antagonist.
Study Design and Patient Population
The study included adults aged 18 to 65 years with a body mass index (BMI) between 18 and 40. Participants were required to have AD affecting 10% or more of their body surface area, an Eczema Area and Severity Index (EASI) score of 12 or greater, and a visual Investigator's Global Assessment (vIGA) score of 3 or greater. The AD cohort consisted of 21 participants receiving a once-daily dose of 400 mg RPT193 and 10 participants receiving a placebo.
Safety and Tolerability
Across all cohorts, treatment-emergent adverse events (TEAEs) were mostly mild or moderate. Headache was the most common TEAE, with most events not related to the study treatment. In the AD cohort, 35.5% of subjects receiving RPT193 400 mg and 20% in the placebo group experienced at least one TEAE, all mild or moderate. No serious adverse events or TEAEs leading to study discontinuation were reported in the AD cohort.
Efficacy Outcomes
Patients treated with RPT193 400 mg QD showed numerically greater improvements in EASI, body surface area, vIGA, and SCORAD scores compared to the placebo group throughout the 28-day treatment period. At Day 29, the percent improvement from baseline in mean EASI score was 36.3% in the RPT193 group, with 42.9% achieving EASI-50, compared to 17.0% and 10.0% in the placebo group.
Sustained Efficacy
Post-hoc analysis at day 43 showed statistically significant differences in several efficacy endpoints, including changes from baseline in mean EASI, proportion of subjects achieving EASI-50, BSA, and SCORAD total scores. This indicates sustained efficacy beyond the treatment period.
Implications
"These data showed that the oral CCR4 antagonist RPT193 was well tolerated and induced clinical improvement and renormalization of the skin transcriptome in subjects with moderate to severe AD," the study authors concluded. "CCR4 antagonists merit further investigation in AD and other diseases where the Th2 axis plays a key role."
