S H Omland1, A Habicht2, P Damsbo3, J Wilms4, B Johansen5, R Gniadecki1,6. 1. Department of Dermato-Venerology, Bispebjerg University Hospital, Copenhagen, Denmark. 2. Signifikans Aps, Vedbaek, Denmark. 3. Avexxin AS, c/o Department of Biology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. 4. Klifo A/S, Glostrup, Denmark. 5. Department of Biology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. 6. Division of Dermatology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
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. OBJECTIVES: 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 withAVX001 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.
RCT Entities:
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. OBJECTIVES: 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.
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