Risk of Squamous Cell Carcinoma on Skin Areas Treated With Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5%

Study Overview
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Brief Summary
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The purpose of the study is to compare the risk of developing squamous skin cancer (SCC) or other types of cancer after treatment of AKs with ingenol mebutate gel or imiquimod cream. Subjects will be randomised to treatment with ingenol mebutate or imiquimod and will receive a second treatment cycle with the same treatment if the first treatment does not clear all AKs. Subjects will be followed over a period of three year (36 months) after first treatment

Official Title
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A Phase 4 Trial Comparing the Cumulative Incidence of SCC After Treatment With Ingenol Mebutate and Imiquimod for Multiple Actinic Keratoses on Face and Scalp. A Multi-centre, Randomised, Two-arm, Open Label, Active-controlled, Parallel Group, 36-month Trial

Conditions
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Actinic Keratosis (AK)

Intervention / Treatment
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* Drug: Ingenol Mebutate Gel, 0.015%
* Drug: Imiquimod Cream, 5%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form (ICF) prior to any trial-related procedures Subjects with 5 to 9 clinically typical, visible and discrete AKs within a contiguous 25 cm² treatment area on the face or scalp. Subject at least 18 years of age Female subjects must be of either: Non-childbearing potential, or, Childbearing potential, provided there is a confirmed negative urine pregnancy test Female subjects of childbearing potential must be willing to use highly effective methods of contraception (Pearl index < 1%) Exclusion Criteria: Location of the selected treatment area: on the periorbital skin on the perioral skin/around the nostrils within 5 cm of an incompletely healed wound within 10 cm of a suspected BCC or SCC or other neoplasia Selected treatment area lesions that have atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horn). History of SCC, BCC, malignant melanoma or other neoplasia in the selected treatment area. History or evidence of skin conditions other than the trial indication that would interfere with evaluation of the trial medication in the selected treatment area Use of ingenol mebutate and/or imiquimod in and within 5 cm of the selected treatment area within 2 years prior to Screening (Visit 1) Organ transplant recipients Immunosuppressed subjects (for example HIV patients) Female subjects who are breastfeeding. Subjects who are institutionalised by court order or by the local authority In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol (e.g. alcoholism, drug dependency or psychotic state)

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ingenol Mebutate<br>Arm A: Ingenol mebutate gel 0.015% applied daily for 3 consecutive days to the selected treatment area followed by 8 weeks' rest. Retreatment for another 3 consecutive days if the treatment field is not completely cleared of AKs at Week 8 | Drug: Ingenol Mebutate Gel, 0.015%<br>* Ingenol mebutate gel 0.015 % (Picato®) applied on the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs.<br>* Other names: Picato®;|
| Active Comparator: Imiquimod<br>Arm B: Imiquimod 5% cream applied 3 days per week for 4 weeks to the selected treatment area followed by 4 weeks' rest. Retreatment for another 4 weeks if the treatment field is not completely cleared of AKs at Week 8 | Drug: Imiquimod Cream, 5%<br>* Imiquimod 5% cream applied to the selected treatment area. Retreatment if the treatment field is not completely cleared of AKs<br>* Other names: Aldara®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of SCC | Cumulative incidence of SCC after treatment with ingenol mebutate gel and imiquimod cream.> The primary response criterion is diagnosis of SCC (defined as invasive SCC i.e. excludes SCC in situ) in the treatment field across the 3-year trial period.> Kaplan-Meier estimate based on time to SCC or censoring. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of SCC and Other Neoplasia | Cumulative incidence of SCC and other neoplasia after treatment with ingenol mebutate gel and imiquimod cream.> The secondary response criterion is diagnosis of SCC and other neoplasia in the treatment field across the 3-year trial period.> Kaplan-Meier estimate based on time to SCC and other neoplasia, or censoring. | 3 years | 
| Number of Participants With Complete Clearance of AK Lesions After Last Treatment | To compare the complete clearance of AK lesions in the selected treatment area after the last treatment cycle (at Week 8 or 16) | 8-16 weeks | 
| Number of Participants With Partial Clearance of AK Lesions | To compare the partial (at least 75%) clearance of AK lesions in the selected treatment area after the last treatment cycle (at Week 8 or 16) | 8-16 weeks | 
| Number of Participants With Complete Clearance of AK Lesions at 12 Months | To compare the complete clearance of AK lesions at 12 months, defined as no AK lesions in the selected treatment area at any time from the last treatment cycle at Week 8 or 16 through to Month 12. | 1 year |