Study to Evaluate Safety and Tolerability of BF-200 ALA (Ameluz®) for Photodynamic Therapy in the Treatment of the Expanded Field of Actinic Keratosis on Face and Scalp

Study Overview
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Brief Summary
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The aim of the study is to evaluate the safety and tolerability of PDT for treatment of mild to severe actinic keratosis on the face and scalp in the expanded treatment field using 3 tubes of BF-200 ALA 10% gel (Ameluz®) in conjunction with the BF-RhodoLED® XL PDT lamp.

Official Title
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A Non-randomized, Open-label, Multicenter Study to Evaluate the Safety and Tolerability of BF-200 ALA (Ameluz®) in the Expanded Field-directed Treatment of Actinic Keratosis on the Face and Scalp With Photodynamic Therapy (PDT)

Conditions
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Actinic Keratosis, Keratosis, Actinic, Keratosis

Intervention / Treatment
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* Combination Product: BF-200 ALA and red light LED lamp


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willingness and ability of subjects to provide informed consent and sign the Health Insurance Portability and Accountability Act (HIPAA) form. A study-specific informed consent and HIPAA form must be obtained in writing prior to starting any study procedures. Subjects with mild to severe clinically confirmed AK lesions (according to Olsen) on the face and/or scalp. In case of severe AK lesions, a biopsy must be taken for confirmation of diagnosis. At least 8 mild to moderate AK lesions with a diameter of ≥4 mm must be present in the treatment field. The treatment field (continuous or in several patches) totaling about 60 cm2 must be located within one effective illumination area. The AK lesions should be clearly distinguishable, without restrictions on the distance between lesions. Lesions should have a minimal distance of 1 cm between the lesion margin and the border of the treatment field. All sexes, ≥18 years of age. Willingness and ability to comply with study procedures, particularly willingness to receive a PDT session and to undergo 2 mm punch biopsy/biopsies in case of severe AK lesion(s) at the screening visit. Subjects with good general health or with clinically stable medical conditions will be permitted to be included in the study. Subjects with clinically stable medical conditions will be permitted for inclusion into the study if not using prohibited medication. Willingness to stop the use of moisturizers and any other non-medical topical treatments within the treatment field at least 24 h prior to the visits. Acceptance to abstain from extensive sunbathing and the use of a solarium or tanning beds during the study. For female subjects with reproductive potential: Negative serum pregnancy test. For female subjects with reproductive potential: Effective contraception at screening visit and throughout the study. Exclusion Criteria: Any known history of hypersensitivity to ALA, porphyrins or excipients of BF-200 ALA. History of soy or peanut allergy. Subjects with sunburn or other possible confounding skin conditions (e.g. wounds, irritations, bleeding or skin infections) inside or in close proximity (<10 cm distance) to the treatment field. Clinically significant (CS) medical conditions making implementation of the protocol or interpretation of the study results difficult or impairing subject's safety such as: Presence of photodermatoses or porphyria Metastatic tumor or tumor with high probability of metastasis Infiltrating skin neoplasia (suspected or known) Unstable cardiovascular disease (New York Heart Association class III, IV) Unstable hematologic (including myelodysplastic syndrome), hepatic, renal, neurologic, or endocrine condition Unstable collagen-vascular condition Unstable gastrointestinal condition Immunosuppressive condition Presence of clinically significant inherited or acquired coagulation defect Clinical diagnosis of atopic dermatitis, Bowen's disease, basal cell carcinoma, eczema, psoriasis, rosacea, squamous cell carcinoma, other malignant or benign tumors inside or in close proximity (<10 cm distance) to the treatment field. Presence of strong artificial pigmentation (e.g. tattoos) or any other abnormality that may impact lesion assessment or light penetration in the treatment field. Any physical therapy such as cryosurgery, laser therapy, electrodessication, microdermabrasion, surgical removal of lesions, curettage, or treatment with chemical peels such as trichloroacetic acid inside or in close proximity (<10 cm distance) to the treatment field within 4 weeks prior to screening. Any of the topical treatments defined below within the designated periods prior to screening: Topical treatment with ALA or ALA esters (e.g. methyl aminolevulinic acid (MAL)) or an investigational drug in- and outside the treatment field within 8 weeks. Topical treatment with immunosuppressive, cytostatic or cytotoxic drugs inside or in close proximity (<10 cm distance) to the treatment field within 8 weeks. Start of topical administration of a medication with hypericin or other drugs with phototoxic or photoallergic potential inside or in close proximity (<10 cm distance) to the treatment field within 4 weeks. Subjects may, however, be eligible if such medication was applied for more than 4 weeks prior to screening without evidence of an actual phototoxic/photoallergic reaction. Any use of the systemic treatments within the designated periods prior to screening: Cytostatic or cytotoxic drugs within 6 months. Immunosuppressive therapies or use of ALA or ALA esters (e.g. MAL) within 12 weeks. Drugs known to have major organ toxicity within 8 weeks or an investigational drug. Interferon or glucocorticosteroids within 6 weeks. Start of intake of medication with hypericin or systemically acting drugs with phototoxic or photoallergic potential within 8 weeks prior to screening. Subjects may, however, be eligible if such medication was taken in for more than 8 weeks prior to the screening visit without evidence of an actual phototoxic/photoallergic reaction. Breast feeding women. Suspicion of drug or alcohol abuse. Subjects unlikely to comply with protocol, e.g. inability to return for visits, unlikely to complete the study, or inappropriate in the opinion of the investigator. A member of study site staff or sponsor staff directly involved in the conduct of the protocol or a close relative thereof. Simultaneous participation in another clinical study. Dosing day exclusion criteria: At Visit 2 (baseline, PDT-1) Subjects with sunburn or other possibly confounding skin conditions (e.g. wounds, irritations, bleeding or skin infections) inside or in close proximity (<10 cm distance) to the treatment field.

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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No

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BF-200 ALA<br>Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). | Combination Product: BF-200 ALA and red light LED lamp<br>* Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²), followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of adverse events (AEs), serious AEs (SAEs), and treatment emergent adverse events (TEAEs). | TEAEs are defined as all AEs with onset or worsening after treatment with IMP up to Visit 5 (approx. 28 days post treatment) | through study completion, an average 6 weeks | 
| Duration of TEAEs including the breakdown of severity category (mild, moderate, severe). |  | from treatment day (day 1) up to Visit 5 (approx. 28 days post treatment) | 
| Assessment of new lesions (AK, NMSC such as BCC, SCC or Bowens disease, and melanoma) if they occur inside the treatment field |  | from treatment day (day 1) up to Visit 5 (approx. 28 days post treatment) | 
| Assessment of new lesions (AK, NMSC, and melanoma) if they occur around the treatment field at a distance of <10 cm |  | from treatment day (day 1) up to Visit 5 (approx. 28 days post treatment) | 
| Application site skin reactions during and post PDT, assessed by the investigator | Application site skin reaction categories: discharge, erosion, erythema, exfoliation, fissure, induration, oedema, scabbing, skin flaking, ulceration, vesicles, other; severity of AE: mild, moderate or severe | from treatment day (day 1) up to Visit 5 (approx. 28 days post treatment) | 
| Application site discomfort during and post PDT, reported by the subjects | Application site discomfort categories: burning, hyperaesthesia, pain, paraesthesia, pruritus, stinging, warmth, other; severity of AE: mild, moderate or severe | from treatment day (day 1) up to Visit 5 (approx. 28 days post treatment) | 
| Application site pain during illumination | Assessed by the subjects using an 11-point numeric rating scale, where a score of 0 means no pain and a score of 10 means worst imaginable pain. | at treatment day (day 1) after end of illumination | 
| Changes in blood pressure (systolic and diastolic) | [mmHg] | at all clinical visits through study completion, on average 6 weeks | 
| Changes in pulse rate | [beats/min] | at all clinical visits through study completion, on average 6 weeks | 
| Changes in body temperature | [°C] | at all clinical visits through study completion, on average 6 weeks | 
| Investigation of clinical chemistry parameters | Findings which differ from reference range and are considered to be clinically significant are to be reported | At screening (up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment) | 
| Investigation of hematology parameters | Findings which differ from reference range and are considered to be clinically significant are to be reported | At screening (up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment) | 
| Investigation of urinalysis parameters | Findings which differ from reference range and are considered to be clinically significant are to be reported | At screening (up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment) | 
| Physical examination of head, neck, skin, lymph nodes, thorax including heart and lungs, abdomen, and musculoskeletal, peripheral vascular and nervous system status | Abnormal findings, considered to be clinically significant, are to be reported | At screening (up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment) | 
| Memory tests | Including picture- and question-based memory tasks; abnormal findings that are considered clinically significant will be documented | At screening (up to 14 days before treatment) and at Visit 2 (treatment day 1) | 
| Neurological investigations | Including investigation of pupils (equality), coordination (finger-nose test), gait (balance), and sensitivity (cheeks, arms, legs); abnormal findings that are considered clinically significant will be documented | At screening (up to 14 days before treatment) and at Visit 2 (treatment day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Actinic keratosis, Photodynamic therapy, 5-aminolevulinic acid, Photosensitizing Agents, Dermatologic Agents, Precancerous condition, Skin Disease