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

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)

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.

Study Overview

• Status: Completed
• Conditions: Keratosis; Actinic Keratosis; Keratosis, Actinic
• Intervention / Treatment: Combination product: BF-200 ALA and red light LED lamp

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Alliance Dermatology & MOHS Center
    • Phoenix, Arizona, United States, 85006
      • Medical Dermatology Specialists
  • Colorado
    • Greenwood Village, Colorado, United States, 80111
      • Dermatology Practice
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Laser and Skin Surgery Center of Indiana
  • New York
    • Rochester, New York, United States, 14623
      • Skin Search of Rochester, Inc
    • Victor, New York, United States, 14564
      • Rochester Dermatologic Surgery
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Clinical Research Center of the Carolinas
  • Texas
    • Houston, Texas, United States, 77056
      • Austin Institute for Clinical Research
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BF-200 ALA; 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; 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Biofrontera Bioscience GmbH

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): April 20, 2023
• Study Completion (Actual): April 20, 2023

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 17, 2021
• First Posted (Actual): September 29, 2021

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: May 3, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Photodynamic therapy; Actinic keratosis; Dermatologic Agents; 5-aminolevulinic acid; Skin Disease; Photosensitizing Agents; Precancerous condition
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: ALA-AK-CT018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes