title: 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%).
  
  
  CONCLUSIONS
  INCB039110 produced significant improvements in sPGA, demonstrating proof of concept in chronic plaque psoriasis.
authors.affiliation: a Innovaderm Research Inc , Montreal , Quebec , Canada .
authors.forename: Robert
authors.initials: R
authors.lastname: Bissonnette
authors.affiliation: b Incyte Corporation , Wilmington , DE , USA , and.
authors.forename: Monica
authors.initials: M
authors.lastname: Luchi
authors.affiliation: b Incyte Corporation , Wilmington , DE , USA , and.
authors.forename: Rosanne
authors.initials: R
authors.lastname: Fidelus-Gort
authors.affiliation: b Incyte Corporation , Wilmington , DE , USA , and.
authors.forename: Shawnta
authors.initials: S
authors.lastname: Jackson
authors.affiliation: b Incyte Corporation , Wilmington , DE , USA , and.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: b Incyte Corporation , Wilmington , DE , USA , and.
authors.forename: Robert
authors.initials: R
authors.lastname: Flores
authors.affiliation: b Incyte Corporation , Wilmington , DE , USA , and.
authors.forename: Robert
authors.initials: R
authors.lastname: Newton
authors.affiliation: b Incyte Corporation , Wilmington , DE , USA , and.
authors.forename: Peggy
authors.initials: P
authors.lastname: Scherle
authors.affiliation: b Incyte Corporation , Wilmington , DE , USA , and.
authors.forename: Swamy
authors.initials: S
authors.lastname: Yeleswaram
authors.affiliation: b Incyte Corporation , Wilmington , DE , USA , and.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Chen
authors.affiliation: c Division of Dermatology , Baylor University Medical Center , Dallas , TX , USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Menter
mesh_terms: D000328:Adult; D000368:Aged; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007539:Isonicotinic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D001384:Azetidines; C000603457:INCB039110; D007539:Isonicotinic Acids; C507904:JAK1 protein, human; D053613:Janus Kinase 1
keywords: Cytokine; JAK-STAT; inflammation; phase 2; psoriasis vulgaris; tyrosine kinase