A Trial to Compare the Incidence of Squamous Cell Carcinoma (SCC) and Other Skin Neoplasia on Skin Areas Treated With Ingenol Disoxate Gel or Vehicle Gel for Actinic Keratosis on Face and Chest or Scalp

Study Overview
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Brief Summary
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One of the main reasons for treating actinic keratoses (AK) is the wish to lower the risk of progression of AK to squamous cell carcinoma (SCC). This risk is in the order of 1 per 1000 AKs per year, which is in itself a small risk, but since patients can have dozens of AKs and the disease is chronic the cumulative risk for a patient can be substantial. In this extension protocol of trials LP0084-1193, -1194, -1195 and -1196, LEO will study the incidence of SCCs and other skin neoplasia in vehicle and ingenol disoxate treated patients over a period of 2 years, so that the total follow-up time for each patient will be 3 years and 2 months.

Official Title
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Incidence of Squamous Cell Carcinoma and Other Skin Neoplasia in Subjects With Actinic Keratosis Treated With Ingenol Disoxate Gel 0.018% or 0.037%, or Vehicle Gel

Conditions
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Actinic Keratosis, Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: ingenol disoxate gel 0.018%
* Drug: ingenol disoxate gel 0.037%
* Other: Vehicle gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent has been obtained. The subject has been treated in one of the trials LP0084-1193, -1194, -1195, or -1196 and has been evaluated at the end of follow-up visit (month 14) of that trial. Exclusion Criteria: The subject is in need of treatment with ingenol mebutate or ingenol disoxate in the selected treatment area . The subject is enrolled in any other interventional clinical trial. For subjects where there is a gap between end of follow-up visit (month 14) in one of the trials LP0084-1193, -1194, -1195, or -1196 and participation in the current trial: The subject has been treated with ingenol mebutate or ingenol disoxate in the selected treatment area after end of follow-up visit (month 14) in one of the trials LP0084-1193, -1194, -1195, or -1196 and until participation in the current trial. The subject has been enrolled in any other interventional clinical trial after end of follow-up visit (month 14) in one of the trials LP0084-1193, -1194, -1195, or -1196 and until participation in the current trial.
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ingenol disoxate gel 0.018%<br> | Drug: ingenol disoxate gel 0.018%<br>* Ingenol disoxate gel is a novel ingenol derivative being developed for field treatment of AKs on treatment areas of up to 250 cm2 (40 in2) on the face, chest and scalp.<br>* Other names: LEO 43204;|
| Experimental: Ingenol disoxate gel 0.037%<br> | Drug: ingenol disoxate gel 0.037%<br>* Ingenol disoxate gel is a novel ingenol derivative being developed for field treatment of AKs on treatment areas of up to 250 cm2 (40 in2) on the face, chest and scalp.<br>* Other names: LEO 43204;|
| Placebo Comparator: Vehicle gel<br> | Other: Vehicle gel<br>* Vehicle to ingenol disoxate gel with no active ingredient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Squamous Cell Carcinoma (SCC) in the Treatment Area | Time to first squamous cell carcinoma (SCC) in the treatment area. Relative difference between groups (ingenol disoxate vs vehicle) expressed as hazard ratio. The indicated measured values are the observed incidence rates of the SCC in the treatment area which form the basis of the statistical analysis of the time to event analysis | From Visit 2 (6 months after Month 14 of main trial) to first SCC in the treatment area, up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Squamous Cell Carcinoma (SCC) or Other Skin Neoplasia in the Treatment Area | Time to first squamous cell carcinoma (SCC) or other skin neoplasia in the treatment area. Relative difference between groups (ingenol disoxate vs vehicle) expressed as hazard ratio. The indicated measured values are the observed incidence rates of the SCC in the treatment area which form the basis of the statistical analysis of the time to event analysis | From Visit 2 (6 months after Month 14 of main trial) to first SCC or other skin neoplasia in the treatment area, up to 24 months |