Efficacy and safety of histamine H 4 receptor antagonist ZPL-3893787 in atopic dermatitis.

BACKGROUND: Histamine 4 (H4 ) receptor antagonists are potential novel treatments for inflammatory skin diseases including atopic dermatitis (AD).

OBJECTIVE: To study the efficacy and safety of ZPL-3893787 (selective H4 receptor antagonist) in moderate/severe AD.

METHODS: A randomised, double-blind, placebo-controlled, parallel-group study was conducted to evaluate ZPL-3893787 (30mg) once daily oral therapy in adult patients with moderate/severe AD. Patients were randomized (2:1), to ZPL-3893787 (n=65) or placebo (n=33) for 8 weeks. Patients had a history of AD for >12 months, Eczema Area and Severity Index (EASI) of ≥12 and ≤48, Investigator's Global Assessment (IGA) ≥3, pruritus score of ≥5 (0-10 scale) and AD of ≥10% body surface area (BSA). Efficacy parameters included EASI, IGA, SCORing Atopic Dermatitis (SCORAD), and pruritus assessment.

RESULTS: Treatment with oral ZPL-3893787 showed a 50% reduction in EASI score compared to 27% for placebo. The placebo-adjusted reduction in EASI score at Week 8 was 5.1; 1-sided p=0.01. Clear or almost-clear IGA scores were 18.5% with ZPL-3893787 vs placebo 9.1%. SCORAD exhibited 41% reduction with ZPL-3893787 vs 26% placebo (placebo-adjusted reduction of 10.0; p=0.004). There was a 3-point reduction (scale 1-10) in pruritus with ZPL-389, but there was a similar reduction with placebo, resulting in a non-significant difference (p=0.249). Patient reported pruritus subscore obtained from SCORAD was reduced with ZPL-3893787 compared to placebo at Week 8 (non-significant). ZPL-3893787 was well tolerated.

CONCLUSION: These results showed for the first time that ZPL-3893787 improved inflammatory skin lesions in patients with AD, confirming H4 receptor antagonism as a novel therapeutic option.