Efficacy and safety of the histamine H4 receptor antagonist ZPL-3893787 in patients with atopic dermatitis

Abstract

Background: H₄ receptor antagonists are potential novel treatments for inflammatory skin diseases, including atopic dermatitis (AD).

Objective: We sought to study the efficacy and safety of ZPL-3893787 (a selective H₄ receptor antagonist) in patients with moderate-to-severe AD.

Methods: A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate ZPL-3893787 (30 mg) once-daily oral therapy in adults with moderate-to-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 more than 12 months, Eczema Area and Severity Index (EASI) scores of 12 or greater and 48 or less, Investigator's Global Assessment (IGA) scores of 3 or greater, pruritus scores of 5 or greater (0- to 10-point scale), and AD on 10% or greater of body surface area. Efficacy parameters included EASI, IGA, SCORAD, and pruritus assessment.

Results: Treatment with oral ZPL-3893787 showed a 50% reduction in EASI score compared with 27% for placebo. The placebo-adjusted reduction in EASI score at week 8 was 5.1 (1-sided P = .01). Clear or almost-clear IGA scores were 18.5% with ZPL-3893787 versus 9.1% with placebo. SCORAD scores exhibited 41% reduction with ZPL-3893787 versus 26% with placebo (placebo-adjusted reduction of 10.0, P = .004). There was a 3-point reduction (scale, 1-10) in pruritus with ZPL-3893787, but there was a similar reduction with placebo, resulting in a nonsignificant difference (P = .249). Patient-reported pruritus subscores obtained from SCORAD were reduced with ZPL-3893787 compared with placebo at week 8 (nonsignificant). ZPL-3893787 was well tolerated.

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

Keywords: Atopic dermatitis; Eczema Area and Severity Index; Investigator's Global Assessment; SCORAD; atopic eczema; eczema; histamine 4 receptor antagonist; pruritus.