Safety and Efficacy of Escalating Doses of LEO 43204 Applied Once Daily for Two Consecutive Days on Approximately 250 cm2 on Trunk and Extremities in Subjects With Actinic Keratosis

Study Overview
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Brief Summary
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Part 1: To identify Maximum Tolerated Dose (MTD) levels of LEO 43204 after once daily treatment for two consecutive days Part 2: To evaluate the efficacy of LEO 43204 in two doses after once daily treatment for two consecutive days compared to vehicle

Official Title
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Safety and Efficacy of Escalating Doses of LEO 43204 Applied Once Daily for Two Consecutive Days on Approximately 250 cm2 on Trunk and Extremities in Subjects With Actinic Keratosis

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: LEO 43204
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the arm Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the extremities or trunk Exclusion Criteria: Location of the treatment area within 5 cm of an incompletely healed wound within 5 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) Prior treatment with ingenol mebutate gel on the treatment area Lesions in the treatment areas that have: atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horns) and/or recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO 43204<br>Open-label, dose-escalation, 2-day treatment | Drug: LEO 43204<br> <br> |
| Experimental: LEO 43204 Dose 0.1%<br>LEO 43204 dose 0.1% once daily for two consecutive days | Drug: LEO 43204<br> <br> |
| Experimental: LEO 43204 Dose 0.075%<br>LEO 43204 dose 0.075% once daily for two days | Drug: LEO 43204<br> <br> |
| Placebo Comparator: Placebo<br>Placebo once daily for two days | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Participants Experiencing Dose Limiting Toxicity (DLT) Based on Local Skin Responses (LSRs) | The number participants experiencing a DLT was used to identify the maximum tolerated dose(MTD) levels of LEO 43204 after once daily treatment for 2 consecutive days.The MTD was defined as the highest dose level at which less than 4 out of 12 participants experienced a DLT. A DLT was defined as one or more of the following three LSRs: Crusting Grade 4 Erosion/Ulceration Grade 4 Vesiculation/Pustulation Grade 4 or two or more of the following five LSRs: Crusting Grade 3 Swelling Grade 4 Erosion/Ulceration Grade 3 Vesiculation/Pustulation Grade 3 or other clinically relevant signs or symptoms observed, which the Investigator judged to be counted as a DLT. The LSRs consists of the following 6 categories: Erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR category was given a numeric grade of severity from 0-4. Grade 0 being no presence and Grade 4 being the highest grade of severity. | From Day 1 up to and including Day 8 | 
| Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Count | Percent reduction from baseline in clinically visible actinic keratosis lesions (AKs) identified in the treatment area. | From baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: Participants With Complete Clearance of AKs (Last Observation Carried Forward [LOCF]) | Complete clearance was defined as a 100% reduction from baseline in AK count. | From baseline to Week 8 | 
| Part 2: Participants With Partial Clearance of AKs (LOCF) | Partial clearance was defined as at least 75% reduction from baseline in AK count. | From baseline to Week 8 |