A dose-finding trial with a novel ingenol derivative (ingenol disoxate: LEO 43204) for field treatment of actinic keratosis on full face or 250 cm² on the chest

Abstract

Purpose: Actinic keratoses (AKs) may progress to squamous cell carcinoma and can occur in cancerized fields as sub-clinical and clinically visible lesions. Ingenol disoxate gel is a topical field therapy for AK. This Phase I/II trial aimed to assess the safety and efficacy of ingenol disoxate on full face or chest in patients with AKs.

Materials and methods: Part 1 was a phase-I, open-label, dose-escalation trial investigating the maximum tolerated dose of ingenol disoxate. Part 2 was a phase-II, randomized, double-blind, vehicle-controlled trial; patients were randomized 1:1:1:1 to ingenol disoxate 0.018%, 0.012%, 0.006% gel or vehicle for 2 consecutive days.

Results: Reduction in AK count from baseline at Week 8 was significantly higher than with vehicle for all doses of ingenol disoxate gel (0.018%, 79.0%; 0.012%, 73.4%; 0.006%, 69.7%; vehicle; 42.3%; p < .001). Local skin responses peaked at Day 3 for all doses, rapidly declined, and reached mild levels at Week 2. Most adverse events were mild or moderate in intensity, and were most commonly application site pain/pruritus.

Conclusions: Ingenol disoxate gel is efficacious and well tolerated as field treatment for AKs on the full face or chest.

Clinical Trial No.: NCT01922050

Keywords:

• Actinic keratosis
• ingenol disoxate
• ingenol mebutate
• field cancerization

Disclosure statement

Dr Bourcier reports industry relationships with AbbVie, Amgen, Celgene, Janssen, Novartis, Pfizer, LEO Pharma, and UCB. Dr Stein Gold has been a consultant and clinical researcher for LEO Pharma. Dr Guenther has been a consultant, speaker, and clinical researcher for LEO Pharma. Dr Andreassen and Dr Selmer are both employees of LEO Pharma. Dr Goldenberg has been a consultant, speaker, and clinical researcher for LEO Pharma.

Additional information

Funding

This study was funded by LEO Pharma (ClinicalTrials.gov, identifier: NCT02124239) and representatives from LEO Pharma were involved in the design and conduct of the trial; collection, management, analysis, and interpretation of data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. None of the authors received financial compensation for authoring the manuscript. Medical writing services were provided by Patrick Griffin, MSc, of iMed Comms, an Ashfield Company, part of UDG Healthcare plc. The protocol and amendments were approved by the Independent Ethics Committee or Institutional Review Board at each study center.