A Randomized Placebo-controlled Clinical Trial of Topical Photodynamic Therapy With 5-aminolevulinic Acid for the Treatment of Actinic Keratosis
Overview
- Phase
- Phase 2
- Intervention
- BF-200 ALA 1%
- Conditions
- Actinic Keratosis
- Sponsor
- Biofrontera Bioscience GmbH
- Enrollment
- 105
- Primary Endpoint
- Total clearance rate of AK lesions
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This was a placebo controlled, double blind, randomized phase II dose-response study to evaluate the efficacy and safety of BF-200 ALA (containing the active ingredient 5 - aminolevulinic acid- ALA) used with photodynamic therapy (PDT) in patients with actinic keratosis (AK).
Detailed Description
The study was performed to define the effective therapeutic dose of the active pharmaceutical ingredient (ALA) in a nanoemulsion formulation in the treatment of actinic keratosis (AK) with topical PDT and to assess the efficacy of topical PDT with a new nanoemulsion formulation of ALA in the treatment of AK. The efficacy of BF-200 ALA was calculated by the AK clearance rate, defined as the proportion of AK lesions showing complete remission 12 weeks after PDT treatment. Subjects of two study centres provided plasma and urine samples for the quantification of ALA and its metabolite, the active photosensitizer protoporphyrin IX (PpIX).
Investigators
Eligibility Criteria
Inclusion Criteria
- •The subjects were willing and able to sign the informed consent form.
- •Men and women aged between 18 and 85 years.
- •Had a general good and stable health condition as confirmed by a physical examination and by medical history.
- •The subjects accepted to abstain from sunbathing and the solarium during the study.
- •The subjects had at least 3 but not more than 10 clinically confirmed AK target lesion of mild to moderate intensity within the face or bald scalp (excluding eyelids, lips and mucosa), i.e. AK grade I and II. Grade I AK lesions presented as flat, pink maculae without signs of hyperkeratosis and erythema.
- •The AK lesions had to be discrete and quantifiable; the distance from one lesion to its neighbour lesion was greater than 1.5 cm.
- •The diameter of each AK lesion was not less than 0.5 cm and not greater than 1.5 cm.
- •The subjects were free of any significant physical abnormalities (e.g., tattoos, dermatoses) in the potential treatment area that could cause difficulty with examination or final evaluation.
- •The subjects were willing to stop using moisturizers and any other topical treatments with anti-aging products, vitamin A, vitamin C, and/or vitamin E containing ointments and creams, and green tea preparations during the study within the treatment area. Sunscreens was allowed, but was not to be applied in the treatment area within approximately 24 hours of a clinic visit with lesion count.
- •Only women of childbearing potential who used a highly effective method of contraception and who had a negative serum pregnancy test were allowed to participate in this study.
Exclusion Criteria
- •Had a known hypersensitivity to ALA.
- •Had received any other medication known to affect AK 3 months before or during the study.
- •Were under immunosuppressive therapy.
- •Suffered from porphyria.
- •Showed hypersensitivity to porphyrins.
- •Suffered from photodermatoses.
- •Had inherited or acquired coagulation defects.
- •Received medication with hypericin or systemically acting drugs with phototoxic or photoallergic potential within 8 weeks prior to treatment with study drug and PDT
- •Had evidence of clinically significant, unstable medical conditions such as
- •a metastatic tumour or a tumour with a high probability of metastatic spread
Arms & Interventions
BF-200 ALA 0%
Topical application of matched placebo gel without containing 5-ALA. Application of a 1 mm thick layer covering each lesion and approximately 1 cm of the surrounding margin.
Intervention: BF-200 ALA 1%
BF-200 ALA 0%
Topical application of matched placebo gel without containing 5-ALA. Application of a 1 mm thick layer covering each lesion and approximately 1 cm of the surrounding margin.
Intervention: BF-200 ALA 3%
BF-200 ALA 0%
Topical application of matched placebo gel without containing 5-ALA. Application of a 1 mm thick layer covering each lesion and approximately 1 cm of the surrounding margin.
Intervention: BF-200 ALA 10%
BF-200 ALA 1%
Topical application of BF-200 ALA gel containing 0.78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and approximately 1 cm of the surrounding margin.
Intervention: BF-200 ALA 1%
BF-200 ALA 3%
Topical application of BF-200 ALA gel containing 3.8 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and approximately 1 cm of the surrounding margin.
Intervention: BF-200 ALA 3%
BF-200 ALA 10%
Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and approximately 1 cm of the surrounding margin.
Intervention: BF-200 ALA 10%
Outcomes
Primary Outcomes
Total clearance rate of AK lesions
Time Frame: 12 weeks after photodynamic therapy (PDT)
Total clearance rate of all AK lesions, defined as the percentage of baseline lesions within the target treatment areas showing complete remission at week 12 post treatment.
Secondary Outcomes
- Local Skin Reactions(during anf after PDT [3h - 4 h])
- Local discomfort(during and after PDT [3h - 4 h])
- Percentage of subjects totally cleared(12 weeks after PDT)
- Overall Cosmetic Outcome(12 weeks after PDT)
- related Adverse Events (AEs)(up to 12 weeks after PDT)
- Reduction of Total Lesion Area(12 weeks after PDT)
- Reduction of Lesion Size(12 weeks after PDT)