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%-5.0%. Safety was assessed as local skin reaction adverse events (LSRAE) grade 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 weeks follow-up with assessment at screening, randomization and once weekly until study end. AVX001 and placebo was applied blinded at symmetrically affected areas once daily.

Results

VX001 was safe with no grade 3-4 LSRAE. A 29% reduction of 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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