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

Phase 1

Completed

• Conditions: Keratosis, Actinic; Actinic Keratosis; Keratosis
• Interventions: Combination Product: BF-200 ALA and red light LED lamp

• Registration Number: NCT05060237
• Lead Sponsor: Biofrontera Bioscience GmbH

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-09-07
• Study First Submitted QC: 2021-09-17
• Study First Posted: 2021-09-29
• Study Start: 2021-12-01
• Primary Completion: 2023-04-20
• Study Completion: 2023-04-20
• Results First Submitted: 2023-10-31
• Status Verified: 2024-10
• Results First Submitted QC: 2024-10-16
• Last Update Submitted: 2024-10-16
• Results First Posted: 2024-10-17
• Last Update Posted: 2024-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 112

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BF-200 ALA	BF-200 ALA and red light LED lamp	Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT).

Primary Outcome Measures

Name	Time	Method
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs).	Through study completion, on average 6 weeks	TEAEs are defined as all AEs with onset or worsening after treatment with IMP up to Visit 5 (Final Visit). TEAEs are considered being related to IMP or medical device, if causal relationship between IMP or medical device and the TEAE is at least possible or relationship assessment is missing. If an AE occurs in different treatment areas (face, scalp, face and scalp), it is reported separately for each treatment area. Thus, some AEs are counted more than once.
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe).	From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)	The duration of TEAEs related to IMP and/or medical device which occurred in at least two subjects and with complete start and stop dates was analyzed. In addition, the proportion of the duration by severity was analyzed. Duration of severity per subject and preferred term is calculated in days counting all days and all episodes of one severity category together. Calculation is done referring to all subjects with occurrence of respective preferred term. If a severity category of a preferred term does not occur in a subject, the duration of this category is set to 0. If an AE occurs in different treatment areas, it is reported separately for each treatment area (face, scalp, face and scalp). Thus, some AEs are counted more than once for the analysis.
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, Visit 2) up to Visit 5 (approx. 28 days post treatment)	Assessed were newly occuring lesions of actinic keratosis (AK), non-melanoma skin cancer (NMSC) such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or Bowens disease, and melanoma inside the treatment field. Cumulative number of lesions is reported.
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, Visit 2) up to Visit 5 (approx. 28 days post treatment)	Assessed were newly occuring lesions of actinic keratosis (AK), non-melanoma skin cancer (NMSC) such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or Bowens disease, and melanoma inside the treatment field. Cumulative number of lesions is reported.
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator	From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)	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
Application Site Discomfort During and Post PDT, Reported by the Subjects	From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)	Application site discomfort categories: burning, hyperaesthesia, pain, paraesthesia, pruritus, stinging, warmth, other; severity of AE: mild, moderate or severe
Application Site Pain During Illumination	At treatment day (day 1, Visit 2) after end of illumination	Assessed by the subjects using an 11-point numeric rating scale (NRS), where a score of 0 means "no pain" and a score of 10 means "worst imaginable pain".
Changes in Blood Pressure (Systolic and Diastolic)	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	Change from baseline is presented. The first measurement at Visit 2 (arrival at site) was considered as baseline value for all following measurements. Blood pressure was measured in mmHg. At Visit 2, photodynamic therapy was performed.
Changes in Pulse Rate	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	Change from baseline is presented. The first measurement at Visit 2 (arrival at the site) was considered as baseline value for all following measurements. Pulse rate was measures in beats/min. At Visit 2, photodynamic therapy was performed.
Changes in Body Temperature	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	Change from baseline is presented. The first measurement at Visit 2 (arrival at site) was considered as baseline value for all following measurements. Body temperature was measured in °F and was converted to °C in the electronic Case Report Form. At Visit 2, photodynamic therapy was performed.
Investigation of Clinical Chemistry Parameters	At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)	Findings which differ from reference range and are considered to be clinically significant are to be reported. Clinical chemistry parameters include glucose, creatinine, total bilirubin, aspartate aminotransferase (AST), alanineaminotransferase (ALT), lactate dehydrogenase (LDH), alkalinephosphatase (AP),gamma glutamyl transferase (GGT), potassium, sodium, calcium, total protein, albumin.
Investigation of Hematology Parameters	At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)	Findings which differ from reference range and are considered to be clinically significant are to be reported. Hematology parameters include hemoglobin, hematocrit, red blood cell count, leukocyte count (white blood cells(WBC)) with differential count (neutrophils, lymphocytes, monocytes, eosinophils, basophils), and platelet count.
Investigation of Urinalysis Parameters	At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)	Findings which differ from reference range and are considered to be clinically significant (CS) are to be reported
Physical Examination of Head, Neck, Skin, Lymph Nodes, Thorax Including Heart and Lungs, Abdomen, and Musculoskeletal, Peripheral Vascular and Nervous System Status	At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)	Abnormal findings, considered to be clinically significant (CS), are to be reported
Memory Tests	At screening (Visit 1, up to 14 days before treatment) and at Visit 2 (treatment day 1)	Including picture- and question-based memory tasks; abnormal findings that are considered clinically significant will be documented
Neurological Investigations	At screening (Visit 1, up to 14 days before treatment) and at Visit 2 (treatment day 1)	Including investigation of pupils (equality), coordination (finger-nose test), gait (balance), and sensitivity (cheeks, arms, legs); abnormal findings that are considered clinically significant (CS) will be documented

Trial Locations

Locations (9)

Clinical Research Center of the Carolinas; 🇺🇸 Charleston, South Carolina, United States

Laser and Skin Surgery Center of Indiana; 🇺🇸 Indianapolis, Indiana, United States

Dermatology Practice; 🇺🇸 Greenwood Village, Colorado, United States

Medical Dermatology Specialists; 🇺🇸 Phoenix, Arizona, United States

Alliance Dermatology & Mohs Center; 🇺🇸 Phoenix, Arizona, United States

Skin Search of Rochester, Inc; 🇺🇸 Rochester, New York, United States

Rochester Dermatologic Surgery; 🇺🇸 Victor, New York, United States

Austin Institute for Clinical Research Inc.; 🇺🇸 Pflugerville, Texas, United States

Austin Institute for Clinical Research; 🇺🇸 Houston, Texas, United States