PMID- 25704750
OWN - NLM
STAT- MEDLINE
DCOM- 20160707
LR  - 20180228
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 173
IP  - 3
DP  - 2015 Sep
TI  - 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.
PG  - 767-76
LID - 10.1111/bjd.13745 [doi]
AB  - 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. OBJECTIVES: 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.
CI  - (c) 2015 The Authors. British Journal of Dermatology published by John Wiley & Sons 
      Ltd on behalf of British Association of Dermatologists.
FAU - Papp, K
AU  - Papp K
AD  - Probity Medical Research, Waterloo, ON, Canada.
FAU - Pariser, D
AU  - Pariser D
AD  - Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, 
      VA, U.S.A.
FAU - Catlin, M
AU  - Catlin M
AD  - MEDTOX Scientific, Inc., St. Paul, MN, U.S.A.
FAU - Wierz, G
AU  - Wierz G
AD  - Astellas Pharma Global Development, Northbrook, IL, U.S.A.
FAU - Ball, G
AU  - Ball G
AD  - Astellas Pharma Global Development, Northbrook, IL, U.S.A.
FAU - Akinlade, B
AU  - Akinlade B
AD  - Astellas Pharma Global Development, Northbrook, IL, U.S.A.
FAU - Zeiher, B
AU  - Zeiher B
AD  - Astellas Pharma Global Development, Northbrook, IL, U.S.A.
FAU - Krueger, J G
AU  - Krueger JG
AD  - The Rockefeller University, New York, NY, U.S.A.
LA  - eng
SI  - ClinicalTrials.gov/NCT01096862
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150619
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Dermatologic Agents)
RN  - 25X51I8RD4 (Niacinamide)
RN  - HPH1166CKX (peficitinib)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Biopsy
MH  - Dermatologic Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Niacinamide/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Psoriasis/*drug therapy/pathology
MH  - Skin/*pathology
MH  - Treatment Outcome
EDAT- 2015/02/24 06:00
MHDA- 2016/07/09 06:00
CRDT- 2015/02/24 06:00
PHST- 2015/02/09 00:00 [accepted]
PHST- 2015/02/24 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2016/07/09 06:00 [medline]
AID - 10.1111/bjd.13745 [doi]
PST - ppublish
SO  - Br J Dermatol. 2015 Sep;173(3):767-76. doi: 10.1111/bjd.13745. Epub 2015 Jun 19.