A randomized, double-blind, placebo-controlled, dose-escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis

Abstract

Background: Chronic plaque psoriasis is partially mediated by elevation of proinflammatory cytokines, including several within the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Objective: To evaluate the safety and efficacy of the oral selective JAK1 inhibitor INCB039110 in stable, chronic plaque psoriasis. Methods: This was a phase 2, randomized, double-blind, placebo-controlled, dose-escalation study of INCB039110 (100 mg once daily, 200 mg once daily, 200 mg twice daily and 600 mg once daily) for 28 days. The primary endpoint was mean percent change from baseline in the static Physician Global Assessment (sPGA) at day 28. The protocol was institutional review board approved. Results: Of 50 patients, 48 completed the study. At day 28, mean percent reduction from baseline in sPGA was 22.2% for INCB039110 100 mg once daily (p  =  0.270 vs. placebo), 29.4% for 200 mg once daily (p  =  0.118), 35.2% for 200 mg twice daily (p  =  0.053), 42.4% for 600 mg once daily (p  =  0.003) and 12.5% for placebo. Across groups, 11.1% to 45.5% achieved an sPGA score of 1 versus 0% for placebo. INCB039110 was generally well tolerated; the most common treatment-emergent adverse event was nasopharyngitis (18.4%). Conclusion: INCB039110 produced significant improvements in sPGA, demonstrating proof of concept in chronic plaque psoriasis.

• Cytokine
• inflammation
• JAK-STAT
• psoriasis vulgaris
• phase 2
• tyrosine kinase

Declaration of Interest

This study was sponsored by Incyte Corporation.

R. Bissonnette has received grants or honoraria as a consultant or investigator for AbbVie, Amgen, Apopharma, Astellas, Celgene, Eli Lilly, Galderma, GSK-Stiefel, Incyte, Kineta, Merck, Isotechnika, Janssen, LEO Pharma, Novartis, and Pfizer.

A. Menter has received grants or honoraria as a consultant, investigator, advisory board member, or speaker for Abbott, Allergan, Amgen, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Novo Nordisk, Pfizer, Stiefel, Syntrix Biosystems, and Wyeth.

S. Jackson, H. Zhang, R. Flores, R. Newton, P. Scherle, S. Yeleswaram, and X. Chen are employes and have stock/stock options with Incyte Corporation.

M. Luchi and R. Fidelus-Gort were employes of Incyte Corporation at the time the study was conducted.

Writing and editorial support was provided by C4 MedSolutions, LLC, and Complete Healthcare Communications, LLC (both ICON plc companies) and was funded by Incyte Corporation.