The oral Janus kinase/spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate-to-severe atopic dermatitis: results from a randomized double-blind placebo-controlled study.

Autor: Bissonnette R; Innovaderm Research Inc., 1851 Sherbrooke Street East, Suite 502, Montreal, H2K 4L5, Quebec, Canada., Maari C; Innovaderm Research Inc., 1851 Sherbrooke Street East, Suite 502, Montreal, H2K 4L5, Quebec, Canada., Forman S; Forward Clinical Trials, Inc., 4915 Ehrlich Road, Tampa, 33624, FL, U.S.A., Bhatia N; Therapeutics Clinical Research, 9025 Balboa Avenue, Suite 105, San Diego, 92123, CA, U.S.A., Lee M; Progressive Clinical Research, P.A., LLC, 1973 North West Loop 410, Suite 106, San Antonio, 78213, TX, U.S.A., Fowler J; Dermatology Specialists Research, 3810 Springhurst Boulevard, Suite 130, Louisville, 40241, KY, U.S.A., Tyring S; Center for Clinical Studies, University of Texas Health Science Center, 451 North Texas Avenue, Houston, 77598, TX, U.S.A., Pariser D; Department of Dermatology, Eastern Virginia Medical School and Virginia Clinical Research Inc., 6160 Kempsville Circle, Suite 200A, Norfolk, 23502, VA, U.S.A., Sofen H; Dermatology Research Associates, 8930 South Sepulveda Boulevard, Los Angeles, 90045, CA, U.S.A., Dhawan S; Center for Dermatology Clinical Research Inc., 2557 Mowry Avenue, Suite 21 and 25, Fremont, 94538, CA, U.S.A., Zook M; Olympian Clinical Research, 1201 South Myrtle Avenue, Clearwater, 33756, FL, U.S.A., Zammit DJ; Asana BioSciences, LLC, 997 Lenox Drive, Suite 220, Princeton Pike Corporate Center, Lawrenceville, 08648, NJ, U.S.A., Usansky H; Asana BioSciences, LLC, 997 Lenox Drive, Suite 220, Princeton Pike Corporate Center, Lawrenceville, 08648, NJ, U.S.A., Denis L; Asana BioSciences, LLC, 997 Lenox Drive, Suite 220, Princeton Pike Corporate Center, Lawrenceville, 08648, NJ, U.S.A., Rao N; Asana BioSciences, LLC, 997 Lenox Drive, Suite 220, Princeton Pike Corporate Center, Lawrenceville, 08648, NJ, U.S.A., Song T; Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Icahn Building 13-76, New York, 10029, NY, U.S.A., Pavel AB; Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Icahn Building 13-76, New York, 10029, NY, U.S.A., Guttman-Yassky E; Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Icahn Building 13-76, New York, 10029, NY, U.S.A.
Jazyk: angličtina
Zdroj: The British journal of dermatology [Br J Dermatol] 2019 Oct; Vol. 181 (4), pp. 733-742. Date of Electronic Publication: 2019 May 06.
DOI: 10.1111/bjd.17932
Abstrakt: Background: ASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved in the pathogenesis of atopic dermatitis (AD) through their regulatory role on T helper (Th)1, Th2 and Th17/Th22 pathways.
Objectives: The objectives of this study were to evaluate the efficacy, safety, pharmacokinetics and effects on systemic biomarkers of ASN002 in patients with moderate-to-severe AD. Methods A total of 36 patients with moderate-to-severe AD were randomized (3 : 1) to ASN002 or placebo in the phase Ib study. Three dosage cohorts were studied over a 28-day period (20 mg, 40 mg and 80 mg once daily).
Results: ASN002 was superior to placebo for the proportion of patients achieving Eczema Area and Severity Index (EASI) 50 (20 mg 20%, P = 0·93; 40 mg 100%, P = 0·003; 80 mg 83%, P = 0·03; placebo 22%), EASI 75 (20 mg 0%, P = 0·27; 40 mg 71%, P = 0·06; 80 mg 33%, P = 0·65; placebo 22%) and in change from baseline in pruritus (20 mg -1·3 ± 2·1, P = 0·81; 40 mg -3·1 ± 2·7, P = 0·27; 80 mg -4·7 ± 2·1, P = 0·01; placebo -1·6 ± 1·8). Adverse events were generally mild and similar across all groups. ASN002 showed dose-dependent plasma exposure with low interpatient variability, significantly downregulated several serum biomarkers involved in Th1, Th2 and Th17/Th22 immunity, and decreased the atherosclerosis-associated biomarker E selectin/SELE.
Conclusions: In patients with moderate-to-severe AD, ASN002 showed strong efficacy with rapid onset of action and associated improvements in systemic inflammation.
(© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)
Databáze: MEDLINE
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