Clinical trial NCT05060237: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Actinic Keratosis
Keratosis, Actinic
Keratosis
Keywords: Actinic keratosis
Photodynamic therapy
5-aminolevulinic acid
Photosensitizing Agents
Dermatologic Agents
Precancerous condition
Skin Disease
Lead sponsor: Biofrontera Bioscience GmbH
Sponsor class: INDUSTRY
First posted: 2021-09-29
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. All sexes, ≥18 years of age.
4. 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.
5. 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.
6. 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.
7. Acceptance to abstain from extensive sunbathing and the use of a solarium or tanning beds during the study.
8. For female subjects with reproductive potential: Negative serum pregnancy test.
9. For female subjects with reproductive potential: Effective contraception at screening visit and throughout the study.

Exclusion Criteria:

1. Any known history of hypersensitivity to ALA, porphyrins or excipients of BF-200 ALA.
2. History of soy or peanut allergy.
3. 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.
4. Clinically significant (CS) medical conditions making implementation of the protocol or interpretation of the study results difficult or impairing subject's safety such as:

   1. Presence of photodermatoses or porphyria
   2. Metastatic tumor or tumor with high probability of metastasis
   3. Infiltrating skin neoplasia (suspected or known)
   4. Unstable cardiovascular disease (New York Heart Association class III, IV)
   5. Unstable hematologic (including myelodysplastic syndrome), hepatic, renal, neurologic, or endocrine condition
   6. Unstable collagen-vascular condition
   7. Unstable gastrointestinal condition
   8. Immunosuppressive condition
   9. Presence of clinically significant inherited or acquired coagulation defect
5. 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.
6. Presence of strong artificial pigmentation (e.g. tattoos) or any other abnormality that may impact lesion assessment or light penetration in the treatment field.
7. 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.
8. Any of the topical treatments defined below within the designated periods prior to screening:

   1. 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.
   2. Topical treatment with immunosuppressive, cytostatic or cytotoxic drugs inside or in close proximity (\<10 cm distance) to the treatment field within 8 weeks.
   3. 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.
9. Any use of the systemic treatments within the designated periods prior to screening:

   1. Cytostatic or cytotoxic drugs within 6 months.
   2. Immunosuppressive therapies or use of ALA or ALA esters (e.g. MAL) within 12 weeks.
   3. Drugs known to have major organ toxicity within 8 weeks or an investigational drug.
   4. Interferon or glucocorticosteroids within 6 weeks.
   5. 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.
10. Breast feeding women.
11. Suspicion of drug or alcohol abuse.
12. 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.
13. A member of study site staff or sponsor staff directly involved in the conduct of the protocol or a close relative thereof.
14. 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.

Primary outcomes:
measure: Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs).
timeFrame: Through study completion, on average 6 weeks
measure: Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe).
timeFrame: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)
measure: Assessment of New Lesions (AK, NMSC Such as BCC, SCC or Bowens Disease, and Melanoma) if They Occur Inside the Treatment Field
timeFrame: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)
measure: Assessment of New Lesions (AK, NMSC, and Melanoma) if They Occur Around the Treatment Field at a Distance of <10 cm
timeFrame: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)
measure: Application Site Skin Reactions During and Post PDT, Assessed by the Investigator
timeFrame: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)
measure: Application Site Discomfort During and Post PDT, Reported by the Subjects
timeFrame: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)
measure: Application Site Pain During Illumination
timeFrame: At treatment day (day 1, Visit 2) after end of illumination
measure: Changes in Blood Pressure (Systolic and Diastolic)
timeFrame: All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment
measure: Changes in Pulse Rate
timeFrame: All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment
measure: Changes in Body Temperature
timeFrame: All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment
measure: Investigation of Clinical Chemistry Parameters
timeFrame: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)
measure: Investigation of Hematology Parameters
timeFrame: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)
measure: Investigation of Urinalysis Parameters
timeFrame: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)
measure: Physical Examination of Head, Neck, Skin, Lymph Nodes, Thorax Including Heart and Lungs, Abdomen, and Musculoskeletal, Peripheral Vascular and Nervous System Status
timeFrame: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)
measure: Memory Tests
timeFrame: At screening (Visit 1, up to 14 days before treatment) and at Visit 2 (treatment day 1)
measure: Neurological Investigations
timeFrame: At screening (Visit 1, up to 14 days before treatment) and at Visit 2 (treatment day 1)
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Medical Dermatology Specialists
state: Arizona
city: Phoenix
country: United States
facility: Alliance Dermatology & Mohs Center
state: Arizona
city: Greenwood Village
country: United States
facility: Dermatology Practice
state: Colorado
city: Indianapolis
country: United States
facility: Laser and Skin Surgery Center of Indiana
state: Indiana
city: Rochester
country: United States
facility: Skin Search of Rochester, Inc
state: New York
city: Victor
country: United States
facility: Rochester Dermatologic Surgery
state: New York
city: Charleston
country: United States
facility: Clinical Research Center of the Carolinas
state: South Carolina
city: Houston
country: United States
facility: Austin Institute for Clinical Research
state: Texas
city: Pflugerville
country: United States
facility: Austin Institute for Clinical Research Inc.
state: Texas
Study officials:
affiliation: Clinical Research Center of the Carolinas, 1364 Ashley River Road, Charleston, SC 29407, USA
name: Todd Schlesinger, MD
role: PRINCIPAL_INVESTIGATOR
References: