Three-day Field Treatment with Ingenol Disoxate (LEO 43204) for Actinic Keratosis: A Phase II Trial

Abstract

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of ingenol disoxate gel using a once-daily, three-day field treatment regimen in patients with actinic keratosis. DESIGN: This was a Phase II, multicenter, open-label trial (clinicaltrials.gov: NCT02305888). SETTING: The study was conducted in 20 trial sites in the United States. PARTICIPANTS: Participants included patients with 5 to 20 clinically typical actinic keratosis lesions on the full face/chest (250cm2), scalp (25-250cm2), or the trunk/extremities (250cm2). MEASUREMENTS: We measured incidence of dose-limiting events based on local skin responses. Percentage reduction in actinic keratosis lesion count from baseline, complete clearance, and partial clearance (≥75%) of actinic keratosis lesions were assessed at Week 8. RESULTS: Nine of 63 (14.3%) patients in the face/chest group reported dose-limiting events; zero of 63 patients in the scalp group reported dose-limiting events; and 11 of 62 (17.7%) patients in the trunk/extremities group reported dose-limiting events. Mean composite local skin response scores peaked at Day 4, then rapidly declined, reaching or approaching baseline levels by Week 4. Less than five percent of patients reported severe adverse events; the most common treatment-related adverse events were application site pain and pruritus. The reduction in actinic keratosis lesion count was 78.9, 76.3, and 69.1 percent for the face/chest, scalp, and trunk/extremities groups, respectively. Complete clearance was achieved in 36.5, 39.7, and 22.6 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. Partial clearance was achieved in 71.4, 65.1, and 50.0 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. CONCLUSION: Ingenol disoxate demonstrated adverse events and local skin reaction profiles similar to results seen in trials evaluating shorter two-day regimens and was effective in patients with actinic keratosis. These data support the use of ingenol disoxate gel for actinic keratosis field treatment.

Keywords: Actinic keratosis; efficacy; field treatment; ingenol disoxate; safety.

Conflict of interest statement

FUNDING:This study was funded by LEO Pharma. DISCLOSURES:Dr. Siegel acknowledges being compensated for lectures and advisory board participation by LEO Pharma within the past two years. Dr. Nahm is an investigator for LEO Pharma. Dr. Petersen and Ms. Østerdal are LEO Pharma employees. Dr. Bermanis a consultant, speaker, and investigator for LEO Pharma. Dr. Tyring has no conflicts of interest relevant to the content of this article.

Figures

FIGURE 1.

Trial design—Times shown are representative of the window within which each visit occurred: screening took place within 35 days of Visit 2; Visits 2 and 3 occurred on Days 1 and 4, respectively; Visits 4 and 5 were conducted at Day 8 and Week 2, respectively ±2 days; Visit 6 occurred at Week 4 ±4 days; Visit 7 was at Week 8 ±7 days. *Represents actual sample size—one patient in the trunk and extremities group was excluded from the full analysis set because of incorrect dose assignment. AK: actinic keratosis; LSR: local skin response

FIGURE 2.

Patient disposition

FIGURE 3.

Composite local skin response (LSR) score: thin lines denote individual scores; bold lines denote mean scores

FIGURE 4.

Individual local skin response (LSR) components by visit

FIGURE 5.

Reduction in actinic keratosis (AK) lesion count at Weeks 4 and 8. Excludes hyperkeratotic/hypertrophic lesions.

FIGURE 6.

Percentage of patients with complete clearance of actinic keratoses (AKCLEAR 100) at Weeks 4 and 8; excludes hyperkeratotic/hypertrophic lesions

FIGURE 7.

Percentage of patients with AKCLEAR 75 at Weeks 4 and 8; excludes hyperkeratotic/hypertrophic lesions AKCLEAR 75: partial clearance of actinic keratoses defined as 75 percent reduction or more in baseline AK lesion count