Controlled Study of the Occurrence of Actinic Keratosis on the Face After Cryotherapy + Aminolevulinic Acid (ALA) Photodynamic Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine if Levulan photodynamic therapy (PDT) is safe and effective in the treatment of actinic keratoses (AK) on the face, following treatment with liquid nitrogen cryotherapy.

Official Title
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A Phase 2 Study Comparing the Occurrence of Actinic Keratoses on the Face in High-Risk Individuals After Cryotherapy + Photodynamic Therapy With Levulan Topical Solution + Blue Light Versus Cryotherapy + Vehicle Topical Solution + Blue Light

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: Aminolevulinic Acid
* Drug: Topical Solution Vehicle
* Device: BLU-U
* Procedure: Cryotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Four to fifteen AKs on the face histologically confirmed presence of abnormal architecture and satellite atypical keratinocytes in the epidermis, in clinically normal tissue samples of photodamaged skin adjacent to AKs at least one previously treated nonmelanoma skin cancer (NMSC) on the head and/or neck area within the past five years Exclusion Criteria: Pregnancy history of cutaneous photosensitization, porphyria, hypersensitivity to porphyrins or photodermatosis lesions suspicious for skin cancer (skin cancer not ruled out by biopsy) or untreated skin cancers within the Treatment Area skin pathology or condition which could interfere with the evaluation of the test product or requires the use of interfering topical or systemic therapy Subject is immunosuppressed unsuccessful outcome from previous ALA-PDT therapy currently enrolled in an investigational drug or device study has received an investigational drug or been treated with an investigational device within 30 days prior to the initiation of treatment known sensitivity to one or more of the vehicle components (ethyl alcohol, isopropyl alcohol, laureth 4, polyethylene glycol) has an active herpes simplex infection OR a history of 2 or more outbreaks within the past 12 months, on the face use of the following topical preparations on the extremity to be treated: Keratolytics including urea (greater than 5%), alpha hydroxyacids [e.g.glycolic acid, lactic acid, etc. greater than 5%], salicylic acid (greater than 2%) within 2 days Retinoids, including tazarotene, adapalene, tretinoin, within 4 weeks Microdermabrasion, laser ablative treatments, ALA-PDT, chemical peels, 5-fluorouracil (5-FU), diclofenac, ingenol mebutate, imiquimod or other topical treatments for AK within 8 weeks use of systemic retinoid therapy within 6 months

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALA X3<br>Cryotherapy followed by 3 aminolevulinic acid + blue light (BLU-U) treatments | Drug: Aminolevulinic Acid<br>* 20% ALA applied to face for one hour prior to 10 J/cm2 blue light<br>* Other names: ALA;Device: BLU-U<br>* 10 J/cm2 blue light delivered at 10 mW/cm2<br>* Other names: BLU-U Blue Light Photodynamic Therapy Illuminator;Procedure: Cryotherapy<br>* Liquid nitrogen cryotherapy by standard of care method to all visible/palpable actinic keratosis (AK) lesions at screening.<br>* Other names: Liquid Nitrogen;|
| Placebo Comparator: VEH<br>Vehicle (VEH) group will be randomized (1:1) to be balanced for the two active groups; receiving cryotherapy and 2 or 3 subsequent Topical Solution Vehicle + BLU-U treatments. Subjects receiving VEH will be considered a single treatment group. | Drug: Topical Solution Vehicle<br>* Levulan Kerastick containing vehicle ingredients only. Vehicle solution applied to face one hour prior to 10 J/cm2 blue light<br>Device: BLU-U<br>* 10 J/cm2 blue light delivered at 10 mW/cm2<br>* Other names: BLU-U Blue Light Photodynamic Therapy Illuminator;Procedure: Cryotherapy<br>* Liquid nitrogen cryotherapy by standard of care method to all visible/palpable actinic keratosis (AK) lesions at screening.<br>* Other names: Liquid Nitrogen;|
| Experimental: ALA X2<br>Cryotherapy followed by 2 aminolevulinic acid + BLU-U treatments | Drug: Aminolevulinic Acid<br>* 20% ALA applied to face for one hour prior to 10 J/cm2 blue light<br>* Other names: ALA;Device: BLU-U<br>* 10 J/cm2 blue light delivered at 10 mW/cm2<br>* Other names: BLU-U Blue Light Photodynamic Therapy Illuminator;Procedure: Cryotherapy<br>* Liquid nitrogen cryotherapy by standard of care method to all visible/palpable actinic keratosis (AK) lesions at screening.<br>* Other names: Liquid Nitrogen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of AKs in Treatment Area | Count of observed lesions in the treatment area, which include lesions that recurred after on-study cryotherapy as well as newly occurring lesions. AK lesions in the treatment area at baseline (maximum of 2) were excluded for this endpoint. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With 0 AKs | Normalized based on number of lesions present at Baseline | Week 4 | 
| Subject Satisfaction Score | Subject satisfaction score = Excellent (very satisfied) = Good (moderately satisfied) = Fair (slightly satisfied) = Poor (not satisfied at all) Unknown | Week 52 | 
| Proportion of Subjects With 0 AKs | Normalized based on number of lesions present at Baseline | Week 12 | 
| Proportion of Subjects With 0 AKs | Normalized based on number of lesions present at Baseline | Week 24 | 
| Proportion of Subjects With 0 AKs | Normalized based on number of lesions present at Baseline | Week 36 | 
| Proportion of Subjects With 0 AKs | Normalized based on number of lesions present at Baseline | Week 52 | 
| Recurrence Rate | Recurrence rate of all lesions that were complete responses following on-study cryotherapy (at Visit 3/Baseline). | Week 52 | 
| Duration of Response | Duration of response is the elapsed number of weeks from the Baseline visit until a lesion recurred or Week 52, whichever comes first | within 52 weeks after Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Actinic Keratosis