Topical application of a novel anti‐interleukin‐17A antibody fragment penetrates psoriatic skin: Results of a randomised, double‐blind, placebo‐controlled Phase Ib study

Abstract

AbstractInterleukin (IL)‐17A underlies the pathogenesis of chronic plaque psoriasis (CPP). Well‐tolerated, effective IL‐17A inhibitors for mild‐to‐moderate CPP are needed. ZL‐1102 is a novel antibody fragment targeting IL‐17A. To assess the safety, tolerability, preliminary efficacy and skin penetration of a topical 1% ZL‐1102 hydrogel in patients with mild‐to‐moderate CPP, a two‐part, Phase Ib study was conducted. Open‐label Part A: six patients received a single topical application of ZL‐1102 onto a psoriatic plaque; double‐blind Part B: 53 patients were randomised 1:1 to twice‐daily ZL‐1102 or vehicle for 4 weeks. Key primary endpoints included treatment‐emergent adverse events (TEAEs), tolerability and changes in local psoriasis area and severity index (PASI). TEAEs occurred in two (33.3%) patients in Part A and in 16 (59.3%) and 13 (50.0%) patients in the ZL‐1102 and vehicle arms, respectively, in Part B. No grade ≥3 TEAEs were seen with ZL‐1102. ZL‐1102 led to numerically greater changes in local PASI versus vehicle (−28.8% vs. −17.2%), with good local tolerability. The trend towards local PASI improvement was accompanied by biomarker changes based on RNA sequencing, indicative of ZL‐1102 penetration into psoriatic plaques. Topical ZL‐1102 showed good safety, local tolerability and a trend towards improved local PASI; skin penetration was observed without measurable systemic exposure. ACTRN12620000700932.