Efficacy and safety of the histamine H4 receptor antagonist ZPL-3893787 in patients with atopic dermatitis - 04/05/19
, Gary Layton, MSc b, Michael Yeadon, PhD c, Lyndsey Whitlock, BSc c, Ian Osterloh, MBBS, MRCP d, Pablo Jimenez, MD c, Wai Liu, PhD c, Victoria Lynch, MD e, Aliya Asher, MD f, Athanasios Tsianakas, MD g, Lynn Purkins, PhD cAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Atopic dermatitis, atopic eczema, eczema, histamine 4 receptor antagonist, Eczema Area and Severity Index, SCORAD, Investigator's Global Assessment, pruritus
Abbreviations used : AD, ANCOVA, EASI, EASI50, EASI75, ECG, FAS, IGA, NRS, PGIC, VRS
Plan
| This study was funded by Ziarco Pharma, who were involved in the study design, collection, analysis, and interpretation of the data; writing of the report; and the decision to submit the article for publication. |
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| Disclosure of potential conflict of interest: T. Werfel's institution got fees for trial visits during the phase 2a study and a grant for laboratory work at the time of the study and travel reimbursements to meetings for the study and consulting fees from Ziarco not directly related to the study. G. Layton was an employee of ParamStat at the time of study, which received an honorarium for his work on the statistical analyses and for reviewing the manuscript. M. Yeadon was CEO of Ziarco Pharma until March 2016 and a consultant for Ziarco from March 2016, a stockholder of the Ziarco Group at the time of the study, and coinventor on a number of patents from Ziarco Pharma at the time of the study; was also cited on a patent that was held by Ziarco Pharma at the time of the study; and received a grant from Innovate UK. L. Whitlock is an employee of Ziarco Pharma Ltd and was a stockholder of Ziarco Group at the time of the study. I. Osterloh is Director of Ostermed and received consulting fees and fees for his participation in review activities for the study. P. Jimenez was an employee of Ziarco Pharma and had private investments in the Ziarco Group at the time of the study. W. Liu was an employee of Ziarco Pharma and was a stockholder of the Ziarco Group at the time of the study, was cited on a patent that was held by Ziarco Pharma at the time of the study, and received a grant to partially fund the phase 2a study from Innovate UK. A. Tsianakas's institution received fees for trial visits during the phase 2a study. L. Purkins was an employee of Ziarco Pharma Ltd at the time of the study, was a stockholder of the Ziarco Group at the time of the study, and was also cited on a patent that was held by Ziarco Pharma at the time of the study. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 143 - N° 5
P. 1830 - mai 2019 Retour au numéro
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