Daylight PDT for Actinic Keratoses: a Multicentre Study Comparing Two Photosensitizers (BF-200 ALA Versus MAL)

Study Overview
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Brief Summary
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This study compares two photosensitizing creams' BF-200 ALA's (aminolevulinic acid, Ameluz®) and MAL's (methyl 5-aminolevulinate, Metvix®) efficacy on actinic keratoses in natural daylight photodynamic therapy (NDL-PDT). The participants' facial skin or scalp will be randomized in two sides and one side is treated with BF-200 ALA and the other side with MAL. Result of the treatment is assessed with clinical examination 12 months after treatment. The investigators will also compare delayed skin reactions after treatment and cost-effectiveness of both photosensitizer creams.

Detailed Description
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Photodynamic therapy (PDT) is a widely used method in dermatology clinics for treatment of superficial skin cancers and premalignant lesions. Actinic keratoses (AKs) are premalignant skin lesions which develop due to long-lasting sun exposure and in time can progress into squamocellular skin cancer if left untreated. The incidence of AKs and skin cancers is rapidly booming as the elderly population increases in western countries. It is crucial to treat AKs early and effectively considering their tendency to progress into malign cancer. The current general consensus for treating AKs is to treat large sun-damaged skin areas simultaneously instead of separate AK lesions. Term skin field cancerization refers to presence of different degrees of visible and invisible dysplastic changes in widely sun-damaged skin. Natural daylight mediated photodynamic therapy (NDL-PDT) is a well-suited method for treating large field-cancerized skin areas. In PDT a photosensitizing cream is applied on the skin and let to absorb. After absorption to the skin cells the photosensitizer changes into protoporphyrin IX (PpIX). PpIX reacts with visible light causing a phototoxic reaction which destroys cancer cells targetedly. After absorption the skin can be illuminated using a red lamp (conventional PDT) or natural daylight (NDL-PDT) as the absorption spectrum peaks of PpIX are within the visual spectrum of light. In Finland the approved photosensitizers for PDT are methyl 5-aminolevulinate cream (MAL, Metvix®, Galderma) and aminolevulinic acid gel (BF-200 ALA, Ameluz®, Biofrontera AG). They both have been clinically studied and proved effective in conventional PDT but in NDL-PDT mainly MAL has been in focus of studies. To our knowledge there is only research report concerning the use of BF-200 ALA in NDL-PDT (Neittaanmaki-Perttu et al 2014) which is a study of our own research group. In this study BF-200 ALA appeared to be more effective than MAL.

Official Title
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Daylight Mediated Photodynamic Therapy for Actinic Keratoses: a Multicentre Study Comparing Two Photosensitizers (BF-200 ALA Versus MAL)

Conditions
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Actinic Keratosis, Natural Daylight Photodynamic Therapy

Intervention / Treatment
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* Drug: Aminolevulinic Acid
* Drug: Methyl 5-aminolevulinate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with widespread AK lesions symmetrically on face or scalp (at least 3 actinic keratoses symmetrically on face or scalp) AKs of grade I-II Exclusion Criteria: Thick grade III AKs Previous treatment for actinic keratosis on the same skin area during preceding 6 months Porfyria or solar dermatitis Allergy for photosensitizers used in the study Pregnant or breastfeeding patients Impaired general condition (patient can't manage required 2 hours in sunlight outdoors)

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Actinic keratosis patients<br>Participant's AKs in facial skin or scalp are first clinically graded and demarcated in two symmetric treatment areas on different sides of face. The areas will be curettaged thinly and next a SPF20 sun protection cream is applied on all sun-exposed areas of the skin. Then a 0,25mm-thick layer of BF-200 ALA (aminolevulinic acid) gel is applied on one treatment side and MAL (methyl 5-aminolevulinate) cream on the other side. The sides will be randomized and the participant doesn't know which side is treated with which light sensitizer. After appropriate absorption time of 30 minutes the patients will be taken to the hospital balcony or yard for 2 hour illumination with natural daylight to accomplish the phototoxic reaction. Maximum dosage of light sensitizer will be 2 grams. | Drug: Aminolevulinic Acid<br>* A 0,25mm-thick layer of BF-200 ALA (aminolevulinic acid, Ameluz®) light sensitizer gel is applied on one randomized treatment side of face.<br>* Other names: Ameluz®;Drug: Methyl 5-aminolevulinate<br>* A 0,25mm-thick layer of MAL (methyl 5-aminolevulinate, Metvix®) light sensitizer cream is applied on one randomized treatment side of face.<br>* Other names: Metvix®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical healing of actinic keratoses | Participant's AKs in the treatment areas are counted and categorized clinically in three grades I-III (Olsen et al. 1991) before the NDL-PDT treatment. The clinical healing of actinic keratoses will be assessed by a dermatologist 12 months after the treatment. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessing pain experienced by participants: comparing the difference in symmetrical treatment areas of face or scalp | Participants will be asked to fill visual analogue scales (VAS) about pain experienced on both treatment sides of the face or scalp. Pain is assessed during the DL-PDT and after the treatment until the evening. | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Actinic Keratosis, Photodynamic Therapy, Natural Daylight