A seamless Phase I/II dose-finding trial assessing ingenol disoxate (LEO 43204) for field treatment of actinic keratosis on the scalp

Abstract

Background

Actinic keratosis (AK) is a common sun-related skin condition, which can progress to squamous cell carcinoma and occur in cancerised fields.

Objectives

This Phase I/II trial investigated the safety and efficacy of ingenol disoxate as topical field therapy for patients with AK on the balding scalp.

Methods

Part 1 was a Phase I, open-label, dose-escalation trial investigating up to 6 doses of ingenol disoxate to determine the maximum tolerated dose (MTD). Part 2 was a Phase II, randomised, double-blind, parallel group, vehicle-controlled trial. Patients were randomised 2:2:1 to receive ingenol disoxate 0.037%, 0.05% or vehicle gel once daily for two consecutive days. Percentage reduction in AK count from baseline, complete clearance (AKCLEAR 100) and partial clearance (>75% AK count reduction; AKCLEAR 75) were assessed at Week 8.

Results

Part 1: the MTD was 0.075% based on a dose-dependent increase in the number and severity of adverse events. Two lower doses of ingenol disoxate gel (0.037%, 0.05%) were assessed in Part 2: reduction in AK count from baseline to Week 8 (0.037%, 72.7%; 0.05%, 78.5% vs vehicle 12.6%, p<0.001), and rates of AKCLEAR 100 and AKCLEAR 75 were significantly higher in active treatment groups compared with vehicle (p≤0.007). Local skin responses peaked at Day 3 and declined rapidly. Adverse events were generally mild to moderate in intensity, and were most commonly application site pain/pruritus.

Conclusion

Ingenol disoxate 0.037% and 0.05% gel was effective and superior to vehicle, and well tolerated as field therapy for AK on the balding scalp.

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