The Copenhagen Actinic Keratosis Study (COAKS). A decentralised clinical trial to evaluate tolerability, safety and efficacy of daily field-directed topical treatment with cytosolic phospholipase A2 inhibitor, AVX001, in participants with actinic keratosis: protocol for a randomised controlled phase I/IIa trial

Abstract

Introduction: Actinic keratosis (AK) is the most common precancerous skin condition caused by long-term UV exposure. Given the high recurrence rate of 15%-53%, identifying safe and effective treatment options is warranted. AVX001, a cytosolic phospholipase A2α (cPLA2α) enzyme inhibitor, is a novel anti-inflammatory drug for field-directed, self-administered, topical therapy of AK.

Methods and analysis: This study is a single-centre, randomised, vehicle-controlled, double-blind, parallel-group hybrid clinical trial in adults with multiple AK lesions Olsen grade 1 or 2. The hybrid design combines decentralised participant tasks and assessments with conventional in-clinic visits. Recruitment using targeted advertising on social media and eligibility prescreening are conducted via the Studies&Me online recruitment platform. Participants (n=60) are randomly assigned to 1 of 3 treatment arms: AVX001 gel 1%, AVX001 gel 3% or vehicle gel. The trial consists of a 4-week treatment period with daily field-directed topical application of the gel and an 8-week follow-up period. Participants attend in-clinic visits at baseline, week 4 and week 12. The remote participant trial tasks include questionnaires and upload of smartphone-obtained photos of the treated skin area using a study-specific web-based app. Both remote and in-clinic assessments of safety and efficacy will be performed. The primary objective is to evaluate the local tolerability of daily application of AVX001 gel (1% or 3%) compared with vehicle gel. Secondary objectives include safety, efficacy, dose-response efficacy relationship, treatment satisfaction and cosmetic outcome. Exploratory objectives include evaluations of tolerability and efficacy assessed by dermatologists using smartphone photos uploaded by participants, comparisons of in-clinic and remote assessments and assessment of AK-related skin changes by non-invasive optical imaging.

Ethics and dissemination: Approved by the Ethics Committee of the Capital Region of Denmark (H-21018064) and the Danish Medicines Agency (2021032485). Results will be submitted for publication in peer-reviewed scientific journals.

Trial registration numbers: 2021-000934-32; NCT05164393.

Keywords: adult dermatology; adverse events; clinical trials; dermatological tumours; dermatology; protocols & guidelines.

Conflict of interest statement

Competing interests: ADA, KK, ACM, CPL, JRZ, API, MLME and ER were employed at Studies&Me for the present work, a clinical research organisation that has been contracted by Coegin Pharma to conduct the present study; TD is the CEO of the sponsor company Coegin Pharma; TD, BJ, AJF and FJA are shareholders and stock option holders of Coegin Pharma; BJ, AJF and FJA have received consulting fees from Coegin Pharma with patents planned; JK is a board member at Coegin Pharma and has received consulting fees from Coegin Pharma; IM has received consulting fees from Studies&Me; VKO has been employed at LEO Pharma AB and has received research grants from Innovation Fund Denmark; MH has received research grants from Studies&Me, LEO Pharma, Lutronic, Mirai Medical and Venus Concept and equipment from Cherry Imaging, Cynosure, Lutronic, Venus Concept, Perfaction Technologies, MiraDry Sientra and Mirai Medical; MH has delivered lectures/teaching for Galderma Nordic.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Overview of trial design. q.d., one time per day; SAi, remote study APP interactions; V, visit; w, week.