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.

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.

• Authors: S H Omland, A Habicht, P Damsbo, J Wilms, B Johansen, R Gniadecki
• Journal: Journal of the European Academy of Dermatology and Venereology : JEADV (J Eur Acad Dermatol Venereol) Vol. 31 Issue 7 Pg. 1161-1167 (Jul 2017) ISSN: 1468-3083 [Electronic] England
• PMID: 28107559 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2017 European Academy of Dermatology and Venereology.

Chemical References

• AVX001
• Fatty Acids, Omega-3
• Phospholipase A2 Inhibitors
• Placebos

Topics

• Administration, Topical
• Adult
• Aged
• Cohort Studies
• Cytosol (enzymology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Fatty Acids, Omega-3 (administration & dosage, adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Phospholipase A2 Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Placebos
• Psoriasis (drug therapy)
• Severity of Illness Index