Investigation of the effective and safe use of the drug product Ameluz in the treatment of actinic keratosis (solar keratosis)
- Conditions
- Actinic keratosis (AK)MedDRA version: 16.0Level: PTClassification code 10000614Term: Actinic keratosisSystem Organ Class: 10040785 - Skin and subcutaneous tissue disordersTherapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2013-002510-12-DE
- Lead Sponsor
- Biofrontera Bioscience GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
• Males or females between 18 and 85 years of age (inclusive)
• Willing and able to sign the informed consent form. A study-specific informed consent must be obtained in writing for all patients before any study procedures
• Presence of 4 to 8 clinically confirmed AK target lesions of mild to moderate intensity within 1-2 fields in the face or bald scalp (excluding eyes, nostrils, ears, and mouth), ie AK grade 1 and 2 according to Olsen et al 1991(1) (for description and grading of AK see Chapter 7.3.1 of the protocol).
To document and confirm the diagnosis of the investigators:
- A pre study biopsy must be taken from a representative AK lesion at the screening visit (Visit 1). The biopsy material will be histopathologically evaluated at a central laboratory by a dermatopathological expert according to the keratinocytic intraepithelial neoplasm (KIN) classification(3-5); (for description and grading of KIN see Chapter 7.3.1 of the protocol).
The result of the biopsy will ultimately determine whether the patient is eligible for participation in this study. Patients may enroll only if the investigator´s clinical diagnosis of AK is confirmed by the histopathological evaluation.
• Willingness to undergo a second biopsy of a representative lesion at the end of study visit (12 weeks after the last PDT) for evaluation
• AK lesions must be discrete and measurable; the lesions have to be located within 1-2 fields of an overall size of approximately 20 cm2
• The diameter of each AK lesion must be between 0.5 cm and 1.5 cm
The size of each baseline AK lesion is determined by measuring the two largest perpendicular diameters. To describe irregular lesions (eg elipsoidal shape), investigators must measure the major and minor axes. The total area of the fields, where the lesions are located, must not exceed 20 cm2.
• Free of significant physical abnormalities (eg tattoos, dermatoses) in the potential treatment region that may complicate examinations or final evaluations
• Willingness to stop using moisturizers, ointments, creams, and any other topical treatments within the treatment region, including anti aging products, or products that contain vitamin A, vitamin D, and/or vitamin E- and green tea preparations, during the study. Sunscreens will be allowed, but they should not be applied to the treatment area within approximately 24 h before a clinical visit that involves lesion counts
• Accept to abstain from extensive sunbathing and the use of a solarium during the period of the clinical visits. Patients experiencing sunburn within the treatment areas cannot be included until they have fully recovered
• Good general health and/or stable health condition, as confirmed by a physical examination and medical history
• Healthy patients or patients with clinically stable medical conditions, including but not limited to the following diseases, will be allowed to participate in the study if their medication is not prohibited by this protocol:
- controlled hypertension
- diabetes mellitus type II
- hypercholesterolemia
- osteoarthritis
• Women of childbearing potential can participate in this study only if they have a negative serum pregnancy test at screening, and are willing to use a highly effective method of contraception. A female is considered to be of childbearing potential if she has a uterus and at least one ovary, has not had a tubal ligation, or is postmenopausal for less than 3 years. Highly effective methods of birth contro
• History of hypersensitivity to 5-ALA or any ingredient of BF-200 ALA
• Current treatment with immunosuppressive therapy
• Presence of porphyria
• Hypersensitivity to porphyrins
• Presence of photodermatoses
• Presence of other malignant or benign tumors of the skin within the treatment area (eg malignant melanoma, BCC or SCC) within the last 4 weeks
• Confirmed diagnosis of SCC for the representative lesion by screening biopsy
• Presence of an inherited or acquired coagulation defect
• Start of intake of medication with hypericin or systemically-acting drugs with phototoxic or photoallergic potential, such as psoralenes, tetracyclines, nalidixic acid, furosemide, amiodarone, phenothiacines, chinolones, fibrates, or phytotherapy with St. John’s wort, arnica, or valerian, or topically applied phototoxic substances like tar, pitch, psoralenes or some dyes like thiazide, methylene blue, toluidine blue, eosine, rose bengal, or acridine within 8 weeks prior to screening. Patients may, however, be enrolled if such medication was stopped 8 weeks prior to screening without evidence for an actual phototoxic/photoallergic reaction. Within 8 weeks prior to screening, such medication must not be newly prescribed. Should such a prescription become unavoidable for medical reasons during the clinical part of the trial, the investigator has to consult with the sponsor, who may discontinue the patient´s study participation, if deemed necessary. Clinically relevant cardiovascular, hepatic, renal, neurologic, endocrine, or other major systemic diseases making the implementation of the protocol or interpretation of the study results difficult
• Evidence of clinically significant (CS), unstable medical conditions such as:
- metastatic tumor or tumor with high probability of metastasis
- cardiovascular disease (New York Heart Association [NYHA] class III, IV)
- immunosuppressive condition
- hematologic, hepatic, renal, neurologic, or endocrine condition
- collagen-vascular condition
- gastrointestinal condition
• Any topical treatment within the treatment area within 12 weeks prior to the first PDT session
• Topical treatment with ALA outside the treatment area during participation in the study
• Topical treatment with MAL during participation in the study
• Topical treatment with immunomodulatory agents (eg imiquimod, ingenol mebutate) 4 weeks prior to the first PDT session
None of the following systemic treatments within the designated period prior to the first PDT session:
Interferon (6 weeks), Immunomodulators or immunosuppressive therapies (10 weeks), Cytotoxic drugs (6 months), Investigational drugs (8 weeks), Drugs known to have major organ toxicity (8 weeks), Corticosteroids (oral or injectable) (6 weeks), Inhaled corticosteroids (>1200 mcg/day for beclomethasone, or >600 mcg/day for fluticasone) (4 weeks), MAL or ALA (12 weeks)
• Pregnancy
• Breast feeding
• Patients with any dermatological disease in the treatment area or surrounding region that may be exacerbated by treatment with topical 5-ALA, or that may cause difficulty with examinations (eg psoriasis, eczema)
• Patients showing cornu cutaneum-like alterations of the skin in the face or on the bald scalp (ie target region)
• Participation in a clinical study within 2 months prior to screening
• Drug or alcohol abuse in the preceding 2 years
• If the patient is the investigator or any sub investigator, research assistant, pharmacist, study coordinator, other st
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to compare the efficacy of BF-200 ALA with placebo, for the field-directed treatment of mild to moderate AK with PDT when using the BF RhodoLED® lamp. <br>;Secondary Objective: To evaluate the safety and secondary efficacy parameters related to BF 200 ALA for field-directed treatment of AK with PDT when using the BF-RhodoLED® lamp. <br>;Primary end point(s): The primary efficacy variable will be the overall patient complete response rate, ie the percentage of patients in which all treated lesions are completely cleared at the assessments performed 12 weeks after the last PDT. ;Timepoint(s) of evaluation of this end point: See definition in sec. E.5.1
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Patient histopathological confirmed response rate<br>2. Patient complete response (complete clearance of all treated lesions) assessed 12 weeks after PDT-1<br>3. Lesion complete response (completely cleared individual lesions) assessed 12 weeks after the last PDT<br>4. Patient partial response (complete clearance of at least 75% of the treated lesions) assessed 12 weeks after the last PDT<br>5. Reduction of total lesion area (the size of all treated lesions added up) per patient 12 weeks after the last PDT<br>6. Overall cosmetic outcome 12 weeks after the last PDT<br>;Timepoint(s) of evaluation of this end point: See definition in sec. E.5.2