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

Rodney Sinclair; Sammy Sharifeh; Susan Thackwray; Jason Lickliter; Junlong Wu; Jing Li; Bei Qi; Philip Bland-Ward; Harald Reinhart

doi:10.1111/exd.14861

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

Journal article

Peer reviewed

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

Rodney Sinclair, Sammy Sharifeh, Susan Thackwray, Jason Lickliter, Junlong Wu, Jing Li, Bei Qi, Philip Bland-Ward and Harald Reinhart

Experimental Dermatology, Vol.32(9), pp.1538-1545

2023

DOI: https://doi.org/10.1111/exd.14861

PMID: 37377276

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Abstract

IL-17A

IL-17A inhibitor

antibody fragment

psoriasis

skin penetration

Interleukin (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.

Details

Title: Topical application of a novel anti‐interleukin‐17A antibody fragment penetrates psoriatic skin: Results of a randomised, double‐blind, placebo‐controlled Phase Ib study
Authors: Rodney Sinclair (Author) - Sinclair Dermatology
Sammy Sharifeh (Author) - Skin Health Institute
Susan Thackwray (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - Legacy
Jason Lickliter (Author) - Royal Brisbane Hospital
Junlong Wu (Author) - Zai Lab (China)
Jing Li (Author) - Zai Lab (China)
Bei Qi (Author) - Zai Lab (China)
Philip Bland-Ward (Author) - Crescendo Biologics Ltd. (Cambridge, United Kingdom)
Harald Reinhart (Corresponding Author) - Zai Lab (China)
Publication details: Experimental Dermatology, Vol.32(9), pp.1538-1545
Publisher: Wiley-Blackwell Publishing Ltd.
DOI: 10.1111/exd.14861
ISSN: 1600-0625
PMID: 37377276
Grant note: Zai Lab
Organisation Unit: University of the Sunshine Coast, Queensland; School of Science and Engineering - Legacy; School of Health and Sport Sciences - Legacy
Language: English
Record Identifier: 99741798102621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Dermatology

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