title: A randomized, double-blind, placebo-controlled, dose-escalation first-in-man study (phase 0) to assess the safety and efficacy of topical cytosolic phospholipase A2 inhibitor, AVX001, in patients with mild to moderate plaque psoriasis.
abstract: BACKGROUND
  Cytosolic phospholipase A2 (cPLA2α) is an enzyme suggested as a therapeutic target in inflammatory skin diseases. AVX001, a cPLA2α inhibitor, was investigated in a randomized, double-blind, placebo-controlled, split-design, first-in-man study in patients with mild to moderate psoriasis.
  
  
  OBJECTIVE
  The primary objective was to evaluate cutaneous safety and tolerability of AVX001 in doses from 0.002% to 5.0%. Safety was assessed as local skin reaction adverse events (LSRAE) grades 3-4. The secondary objective was assessment of efficacy on modified PASI (mPASI) score compared with placebo.
  
  
  METHODS
  Of 94 randomized men, 88 completed treatment with AVX001 and placebo. The treatment period was four weeks with two-week follow-up with assessment at screening, randomization and once weekly until study end. AVX001 and placebo were applied blinded at symmetrically affected areas once daily.
  
  
  RESULTS
  AVX001 was safe with no grades 3-4 LSRAE. A 29% reduction in mPASI was seen at the 5% dose level at week four. Post hoc analysis of combined doses of 3% and 5% showed a clinical relevant effect with 31% reduction in mPASI (P = 0.058) and statically significant reduction of the infiltration (P = 0.036). The actively treated side showed improvement in mPASI score after one week of treatment, and the observed improvement continued throughout the four weeks of treatment.
  
  
  CONCLUSIONS
  Treatment with AVX001 is well tolerated in doses up to 5%, and showed placebo-adjusted, clinical effects at a level of statistical significance. The improvement throughout the treatment period suggests that longer treatment could conceivably result in superior efficacy.
authors.affiliation: Department of Dermato-Venerology, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: S H
authors.initials: SH
authors.lastname: Omland
authors.affiliation: Signifikans Aps, Vedbaek, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Habicht
authors.affiliation: Avexxin AS, c/o Department of Biology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: P
authors.initials: P
authors.lastname: Damsbo
authors.affiliation: Klifo A/S, Glostrup, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Wilms
authors.affiliation: Department of Biology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: B
authors.initials: B
authors.lastname: Johansen
authors.affiliation: Department of Dermato-Venerology, Bispebjerg University Hospital, Copenhagen, Denmark.|Division of Dermatology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Gniadecki
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003600:Cytosol / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064801:Phospholipase A2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D011565:Psoriasis / Q000188:drug therapy*; D012720:Severity of Illness Index
chemical_list: C580854:AVX001; D015525:Fatty Acids, Omega-3; D064801:Phospholipase A2 Inhibitors; D010919:Placebos