Daylight-PDT for AKs: Comparing Two Photosensitizers (BF-200 ALA and MAL)

Phase 4

Completed

Conditions: Multiple Actinic Keratoses

Interventions: Drug: BF-200 ALA cream
Drug: MAL cream

Registration Number: NCT01893203

Lead Sponsor: Joint Authority for Päijät-Häme Social and Health Care

Brief Summary: The aim of the study is to compare the efficacy of two photosensitizers, methyl-aminolaevulinate (MAL) and 5-aminolaevulinic nanoemulsion (BF-200 ALA) in the treatment of facial actinic keratosis. We use randomized, double-blinded prospective study design. The efficacy will be assessed clinically, histopathologically and immunohistochemically.

Detailed Description: Actinic keratoses (AKs) are superficial premalignant skin lesions that can progress into an invasive or metastatic squamous cell carcinoma. AKs can be treated with photodynamic therapy (PDT), of which cure rate compares to cryo surgery with an excellent cosmesis. In PDT the AK lesions are first curettaged, then a photosensitizer is applied on the skin and let to absorb for 3 hours. The skin is illuminated using a blue or red light source light source depending on the photosensitizer, which induces activation of protoporphyrin IX (PpIX) and phototoxic reaction destroying the cancer cells.

The approved photosensitizers in Europe are methyl-aminolevulinic acid cream, (MAL, Metvix™, Galderma), a patch containing 5-aminolevulinic acid (5-ALA, Alacare®, Spirig AG) and 5-aminolevulinic acid gel (BF-200 ALA, Ameluz®, Biofrontera AG) to be used with a red LED light (630-635 nm). In North America a 5-aminolevulinic acid stick (5-ALA, Levulan® Kerastick) can also be used with a blue light source (417 nm).

PpIX absorption peaks are within the visual spectrum of light, which allows PpIX daylight activation. During natural daylight PDT (NDL-PDT) protocol, PpIX is continuously activated during its development, whereas in conventional PDT (LED-PDT) using red LED lamps, large amounts of accumulated PpIX are momentarily activated.

Since skin field cancerization refers to presence of different degrees of visible and invisible dysplastic changes, the whole area should be treated to prevent the development of non-melanoma skin cancers (NMSCs). NDL-PDT enables treatment of field cancerization in one sitting whereas LED-PDT may need repeated illuminations to cover the whole area. NDL-PDT results in enhanced cost-efficacy due to reduced staff expenses, since there's no need for sensitizer absorption and illumination.

At the moment two photosensitizers have marketing authorization in Finland, ALA (Ameluz®) and MAL (Metvix™). We are piloting a study comparing the efficacy of these two light sensitizers in NDL-PDT. The efficacy of the treatments will be assessed clinically, histopathologically and immunohistochemically.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

Inclusion Criteria

actinic keratoses symmetrically on face or scalp
age over 18 years
there must be at minumum one ak sized 6mm2 symmetrically on both sides
patients must be able to make the decision to attend independently

Exclusion Criteria

pregnancy
lactation
lack of compliance

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BF-200 ALA vs MAL	BF-200 ALA cream	BF-200 ALA cream and MAL (Metvix, Galderma) used in a randomized split-face design
BF-200 ALA vs MAL	MAL cream	BF-200 ALA cream and MAL (Metvix, Galderma) used in a randomized split-face design

Primary Outcome Measures

Name	Time	Method
Histological Lesion Clearance	0 (baseline) and 3 months	Punch biopsies were taken symmetrically on both treatment fields from equally graded \>6 mm AKs prior to treatment and again at 3 months, blinded observer (pathologist). HE- and p53-stainings. Samples not fulfilling the criteria of an AK were defined as healthy or completely cleared. The p53 reactivity expressed as average percentage of positive nuclei in three consecutive high power fields from the region of highest reactivity (\<10 % normal)

Secondary Outcome Measures

Name	Time	Method
Pain	12 hours	Pain using visual analog scale (VAS 0-10, where 0 is no pain and 10 is the worst pain imaginable) on both treatment sides is assessed in every 30 minutes during 2-hour sun-exposure and afterwards once in two hours until 9 p.m. (treatment day). Of these values, the mean maximal pain is assessed.
Clinical Lesion Clearance	3 months	Clinical lesion clearance is observed by a blinded observer