Evaluation of Safety and Efficacy of BF-200 ALA for the Treatment of Actinic Keratosis With Photodynamic Therapy

A Randomized, Observer Blind, Multinational Phase III Study to Evaluate the Safety and Efficacy of a Nanoemulsion Gel Formulation BF-200 ALA, in Comparison With Metvix® and Placebo, for the Treatment of Actinic Keratosis With PDT

The aim of the study is to evaluate the non-inferiority of BF-200 ALA (Ameluz) in the treatment of actinic keratosis (AK) with photodynamic therapy (PDT) compared to Metvix.

This was a randomized, observer-blind, multinational, comparator and placebo-controlled parallel group, (3:3:1 ratio) study to compare the efficacy and safety of BF-200 ALA with the comparator Metvix® (methyl-[5-amino-4-oxopentanoate]) and placebo, for the treatment of AK with PDT.

Main Inclusion Criteria:

• Written informed consent.
• Men and women between 18 and 85 years of age.
• 4-8 AK lesions of 0.5 to 1.5 cm diameter of mild to moderate intensity (Olsen grade 1 and 2) in the face and/or on the bald scalp. Lesions on the eyes, nostrils, ears and mouth were not considered for treatment during the planned study.
• Target AK lesions were to be discrete and quantifiable; adjacent AK lesions were to show a minimum distance of 1.0 cm from one another.
• Confirmation of AK by biopsy taken at screening.
• Free of significant physical abnormalities (e.g., tattoos, dermatoses) in the potential treatment region that could have caused difficulty with examination or final evaluation.
• Willingness to stop the use of moisturizers and any other topical treatments within the treatment region.
• Good general health condition.
• Healthy subjects and subjects with clinically stable medical conditions including, but not limited to the following diseases (controlled hypertension, diabetes mellitus type II, hypercholesterolemia, osteoarthritis) were permitted to be included in the study if the medication taken for the treatment of the disease did not match an exclusion criterion or was not specified as prohibited concomitant medication.
• No extensive sunbathing or solarium use during the trial.
• Negative pregnancy test at screening.

Main exclusion criteria:

• Known hypersensitivity to BF-200 ALA, MAL (methyl-aminolevulinic acid) and/or any of the ingredients of the formulations
• Clinically significant medical conditions (tumor disease etc.) making implementation of the protocol or interpretation of the study results difficult
• Presence of photodermatoses
• Presence of other tumors in the treatment areas within the last 4 weeks
• Start of treatment with phototoxic or photoallergic drugs within 8 weeks prior to screening
• Current treatment with immunosuppression therapy
• Hypersensitivity to porphyrins
• Presence of porphyria
• Presence of inherited or acquired coagulation defect
• Any topical treatment within the treatment area within 12 weeks before PDT1 (first PDT Treatment)
• Topical treatment with ALA or MAL outside the treatment area during participation in the study
• None of the specified systemic treatments within the designated period before PDT1