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

• ClinicalTrials.gov Identifier: NCT05060237
• Recruitment Status: Recruiting
• First Posted: September 29, 2021
• Last Update Posted: February 10, 2023
• Sponsor: Biofrontera Bioscience GmbH
• Information provided by (Responsible Party): Biofrontera Bioscience GmbH

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Actinic Keratosis; Keratosis, Actinic; Keratosis	Combination Product: BF-200 ALA and red light LED lamp	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: December 1, 2021
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: March 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Frequency and severity of adverse events (AEs), serious AEs (SAEs), and treatment emergent adverse events (TEAEs). [ Time Frame: through study completion, an average 6 weeks ]
   TEAEs are defined as all AEs with onset or worsening after treatment with IMP up to Visit 5 (approx. 28 days post treatment)
2. Duration of TEAEs including the breakdown of severity category (mild, moderate, severe). [ Time Frame: from treatment day (day 1) up to Visit 5 (approx. 28 days post treatment) ]
3. Assessment of new lesions (AK, NMSC such as BCC, SCC or Bowens disease, and melanoma) if they occur inside the treatment field [ Time Frame: from treatment day (day 1) up to Visit 5 (approx. 28 days post treatment) ]
4. Assessment of new lesions (AK, NMSC, and melanoma) if they occur around the treatment field at a distance of <10 cm [ Time Frame: from treatment day (day 1) up to Visit 5 (approx. 28 days post treatment) ]
5. Application site skin reactions during and post PDT, assessed by the investigator [ Time Frame: from treatment day (day 1) 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
6. Application site discomfort during and post PDT, reported by the subjects [ Time Frame: from treatment day (day 1) 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
7. Application site pain during illumination [ Time Frame: at treatment day (day 1) after end of 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".
8. Changes in blood pressure (systolic and diastolic) [ Time Frame: at all clinical visits through study completion, on average 6 weeks ]
   [mmHg]
9. Changes in pulse rate [ Time Frame: at all clinical visits through study completion, on average 6 weeks ]
   [beats/min]
10. Changes in body temperature [ Time Frame: at all clinical visits through study completion, on average 6 weeks ]
    [°C]
11. Investigation of clinical chemistry parameters [ Time Frame: At screening (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
12. Investigation of hematology parameters [ Time Frame: At screening (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
13. Investigation of urinalysis parameters [ Time Frame: At screening (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
14. Physical examination of head, neck, skin, lymph nodes, thorax including heart and lungs, abdomen, and musculoskeletal, peripheral vascular and nervous system status [ Time Frame: At screening (up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment) ]
    Abnormal findings, considered to be clinically significant, are to be reported
15. Memory tests [ Time Frame: At screening (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
16. Neurological investigations [ Time Frame: At screening (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 will be documented

Eligibility Criteria

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

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.

Contacts and Locations

Contacts

Contact: Corinna Zogel, Dr.; +49 214 3119772207; c.zogel@biofrontera.com

Locations

United States, Arizona

Medical Dermatology Specialists; Recruiting

Phoenix, Arizona, United States, 85006

Contact: Nathalie Zeitouni, MD 602-354-5770

Alliance Dermatology & Mohs Center; Recruiting

Phoenix, Arizona, United States, 85032

Contact: Sasha Jazayeri, MD 602-971-0268

United States, Colorado

Dermatology Practice; Recruiting

Greenwood Village, Colorado, United States, 80111

United States, Indiana

Laser and Skin Surgery Center of Indiana; Recruiting

Indianapolis, Indiana, United States, 46260

Contact: C. William Hanke, MD 317-660-4900

United States, New York

Skin Search of Rochester, Inc; Recruiting

Rochester, New York, United States, 14623

Contact: John H. Tu, MD 585-697-1818

Rochester Dermatologic Surgery; Recruiting

Victor, New York, United States, 14564

Contact: Sherrif F Ibrahim, MD 585-222-1400

United States, South Carolina

Clinical Research Center of the Carolinas; Recruiting

Charleston, South Carolina, United States, 29407

Contact: Todd E. Schlesinger, MD 843-556-8886

United States, Texas

Austin Institute for Clinical Research; Recruiting

Houston, Texas, United States, 77056

Contact: Megan Poynot Couvillion, MD 713-985-0210

Austin Institute for Clinical Research Inc.; Recruiting

Pflugerville, Texas, United States, 78660

Contact: Edward L Lain, MD 512-279-2545

Sponsors and Collaborators

Biofrontera Bioscience GmbH

Investigators

• Principal Investigator: Todd Schlesinger, MD; Clinical Research Center of the Carolinas, 1364 Ashley River Road, Charleston, SC 29407, USA

More Information

• Responsible Party: Biofrontera Bioscience GmbH
• ClinicalTrials.gov Identifier: NCT05060237
• Other Study ID Numbers: ALA-AK-CT018
• First Posted: September 29, 2021
• Last Update Posted: February 10, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Biofrontera Bioscience GmbH:

Actinic keratosis; Photodynamic therapy; 5-aminolevulinic acid; Photosensitizing Agents; Dermatologic Agents; Precancerous condition; Skin Disease

Additional relevant MeSH terms:

Keratosis, Actinic; Keratosis; Skin Diseases; Precancerous Conditions; Neoplasms; Aminolevulinic Acid; Photosensitizing Agents; Dermatologic Agents