title: A phase 2a randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate-to-severe psoriasis.
abstract: BACKGROUND
  Many immune-mediated disorders, including psoriasis, involve cytokine signalling via Janus kinase (JAK) enzymes. ASP015K (also designated JNJ-54781532), a novel oral JAK inhibitor, has shown moderate selectivity for JAK3 over JAK1 and JAK2 in enzyme assays.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the efficacy and safety of escalating, sequentially grouped, doses of ASP015K vs. placebo in patients with moderate-to-severe psoriasis.
  
  
  METHODS
  This phase 2a multicentre, double-blind, randomized, placebo-controlled study (NCT01096862) enrolled 124 patients with moderate-to-severe plaque psoriasis. Five sequential ASP015K cohorts were enrolled, consisting of four twice-daily dosing groups (10, 25, 60, 100 mg) and one once-daily dosing group (50 mg) for 6 weeks.
  
  
  RESULTS
  The primary efficacy end point [mean change in Psoriasis Area and Severity Index score from baseline to end of treatment (EOT; day 42)] significantly favoured ASP015K (overall treatment effect; P < 0.001) vs. placebo, with greater improvements at higher doses. By EOT, the secondary end points [Physician Static Global Assessment (PSGA) score, percentage of patients achieving PSGA success, and change in percentage, body surface area (BSA)] also improved with ASP015K vs. placebo (P < 0.001 for PSGA score and BSA; P < 0.01 for PSGA success). Epidermal thickness and proliferation decreased from baseline with ASP015K vs. placebo. ASP015K was generally well tolerated, with no serious adverse events (AEs) reported.
  
  
  CONCLUSIONS
  In patients with moderate-to-severe psoriasis, ASP015K demonstrated dose-dependent improvements in clinical and histological measures of severity over 6 weeks of treatment. At all doses, ASP015K was well tolerated, with no reported serious AEs.
authors.affiliation: Probity Medical Research, Waterloo, ON, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Papp
authors.affiliation: Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA, U.S.A.
authors.forename: D
authors.initials: D
authors.lastname: Pariser
authors.affiliation: MEDTOX Scientific, Inc., St. Paul, MN, U.S.A.
authors.forename: M
authors.initials: M
authors.lastname: Catlin
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, U.S.A.
authors.forename: G
authors.initials: G
authors.lastname: Wierz
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, U.S.A.
authors.forename: G
authors.initials: G
authors.lastname: Ball
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, U.S.A.
authors.forename: B
authors.initials: B
authors.lastname: Akinlade
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, U.S.A.
authors.forename: B
authors.initials: B
authors.lastname: Zeiher
authors.affiliation: The Rockefeller University, New York, NY, U.S.A.
authors.forename: J G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001706:Biopsy; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D012867:Skin / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D003879:Dermatologic Agents; D009536:Niacinamide; C000608065:peficitinib; D000218:Adamantane