PEP005 Gel - Biological Effects in Actinic Keratosis Assessed by Histology

Study Overview
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Brief Summary
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This trial will be conducted to explore the biological effects in the skin following treatment with PEP005 Gel, 0.05% administered for two consecutive days, assessed by histology.

Official Title
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A Phase I, Single-centre, Open Label, Within-subject Comparison Trial to Explore the Biological Effects of PEP005 (Ingenol Mebutate) Gel, 0.05%, Applied Once Daily for 2 Consecutive Days in Patients With Actinic Keratosis on the Upper Extremity

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: PEP005 (Ingenol mebutat Gel, 0.05 %)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients at least 18 years of age Patients with AK lesions within a contiguous 25 cm2 area on the upper extremity Patients with a 25 cm2 area of normal skin on the upper inner arm Female subjects must be of either non-childbearing potential or childbearing potential, provided there is a confirmed negative urine pregnancy test prior to exposure, to rule out pregnancy Female subjects of childbearing potential must be willing to consent to using high effective methods of contraception Ability to follow study instructions and likely to complete all study requirements Obtained written informed consent prior to any study-related procedures Exclusion Criteria: Location of the selected treatment areas within 5 cm of an incompletely healed wound within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) History or evidence of skin conditions other than the study indication that would interfere with evaluation of the study medication Clinical diagnosis/history or evidence of any medical condition that would expose a subject to an undue risk of a significant AE or interfere with assessments of safety, as determined by Investigator clinical judgment. Anticipated need for in-patient hospitalisation or in-patient surgery during the study period. Current participation in any other interventional clinical trial Subjects who have received treatment with any non-marketed drug product within the last two months Subject known or, in the opinion of the investigator, is unlikely to comply with the Clinical Study Protocol Females who are pregnant, of child-bearing potential and wishing to become pregnant during the trial, or are breast feeding Undergone cosmetic or therapeutic procedures within 2 cm of the selected treatment areas in the 2 weeks prior to the screening visit Use of acid-containing therapeutic products within 2 cm of the selected treatment areas in the 2 weeks prior to the screening visit Use of topical salves/topical steroids: within 2 cm of the selected treatment areas in the 2 weeks prior to the screening visit Treatment with immunomodulators, cytotoxic drugs or interferon/interferon inducers, systemic medications that suppress the immune system or UVB in the last 4 weeks Treatment with 5-FU, imiquimod, diclofenac, or photodynamic therapy: within 2 cm of the selected treatment areas within 8 weeks prior to any screening visit Use of systemic retinoids

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

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ingenol mebutate<br>PEP gel 0.05% once daily exposure | Drug: PEP005 (Ingenol mebutat Gel, 0.05 %)<br>* All eligible patients will receive PEP005 Gel, 0.05 %, on two consecutive days to both the AK Treatment Area and the Normal Skin Treatment Area<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leukocytes Infiltration and degree of necrosis of the AK lesion and skin | Degree of skin infiltration of leukocytes and necrosis of the epidermis and dermis in the AK biopsies from Day 1, Day 2, and Day 3 | From baseline until day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biological effects in the skin | Leukocytes Infiltration Degree of skin infiltration of leukocytes Necrosis Haemorrhage Immune cell activation Apoptosis Endothelium activation RNA expression Drug Transporter Number of participants with changes in normal skin and AK lesion biopsies | from baseline till day day 3 |