Clinical trial NCT05662202: Study to Evaluate the Safety, Tolerability and Efficacy of BF-200 ALA (Ameluz®) in the Field-directed Treatment of Actinic Keratosis (AK) on the Extremities and Neck/Trunk With Photodynamic Therapy (PDT) Using a RhodoLED Lamp
Official title: A Randomized, Double-blind, Vehicle-controlled, Multicenter Phase III Study to Evaluate the Safety, Tolerability, and Efficacy of BF-200 ALA (Ameluz®) in the Field-directed Treatment of Actinic Keratosis on the Extremities and Neck/Trunk With Photodynamic Therapy (PDT) Using the BF-RhodoLED® XL or BF-RhodoLED® Lamp
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Actinic Keratoses
Keywords: Actinic keratosis
Photodynamic therapy
5-aminolevulinic acid
Photosensitizing Agents
Lead sponsor: Biofrontera Bioscience GmbH
Sponsor class: INDUSTRY
First posted: 2022-12-22
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to test the safety. tolerability and efficacy of field-directed photodynamic therapy (PDT) with 10% aminolevulinic acid gel (Ameluz®, BF-200 ALA) in combination with one of the narrow spectrum red light RhodoLED lamps in comparison to vehicle treatment for actinic keratosis (AK) on the extremities and neck/trunk.


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. 4 - 15 mild to moderate clinically confirmed AK lesions according to Olsen either on the extremities or on the neck/trunk with a diameter of ≥ 4 mm that must be present in the treatment field (defined as AK target lesions). In addition, non-target AK lesions may be present in the treatment field, including up to two severe AK lesions ≥ 4 mm. For each severe AK lesion (≥ 4 mm), a biopsy must be taken for confirmation of diagnosis. The treatment field (continuous or in several patches) totaling approx. either 80 cm², 160 cm² or 240 cm2 must be within one effective illumination area of the BF-RhodoLED® XL but may require up to three illuminations with the BF-RhodoLED®. All AK target lesions and, if applicable, severe AK lesions ≥ 4 mm located in the treatment field should be clearly distinguishable, without restrictions on the distance between lesions, and should have a minimal distance of 1 cm to the border of the treatment field.
3. All sexes, ≥ 18 years of age.
4. Willingness to undergo a 2 mm punch biopsy for each (up to two) severe AK lesion ≥ 4 mm, if applicable, at the screening visit.
5. Willingness and ability to comply with study procedures, particularly willingness to receive up to 2 PDTs within approximately 12 weeks.
6. Subjects with good general health or with clinically stable medical conditions will be permitted to be included in the study.
7. 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 next clinical visit.
8. Acceptance to abstain from extensive sunbathing and the use of a solarium or tanning beds during the treatment phase.
9. For female subjects with reproductive potential: Negative serum pregnancy test.
10. For female subjects with reproductive potential: Effective contraception at screening visit and throughout the treatment phase of the study (until Visit 4 or Visit 6).

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. Sunburn or other possible confounding skin conditions (e.g., wounds, irritations, bleeding, or skin infections) inside or in close proximity (\< 2 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 (BD), basal cell carcinoma (BCC), eczema, psoriasis, rosacea, squamous cell carcinoma (SCC), other malignant or benign tumors inside or in close proximity (\< 2 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 cryotherapy, 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)) inside the treatment field within 3 months.
   2. Topical treatment with immunomodulatory, cytostatic, or cytotoxic drugs inside or in close proximity (\< 10 cm distance) to the treatment field within 3 months.
   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 ALA or ALA esters (e.g., MAL) within 12 weeks.
   3. Drugs known to have major organ toxicity within 8 weeks.
   4. Interferon or glucocorticosteroids within 6 weeks.
   5. Start of intake of medication with hypericin or 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. Receipt of any investigational drug or medical product within 8 weeks before screening or simultaneous participation in another clinical study.

Reassessment of subjects is allowed once in case exclusion criterion 3 is met and eligibility can be achieved within 4 weeks. Reassessment can be done on the day of the actual treatment.

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 (\< 2 cm distance) to the treatment field. Reassessment of subjects is allowed once if the sunburn or other confounding skin conditions is/are expected to resolve within 2 weeks.

At Visit 4 (PDT-2)

Subjects with sunburn or other possibly confounding skin conditions (e.g., wounds, irritations, bleeding, or skin infections) inside or in close proximity (\< 2 cm distance) to the treatment field. Rescheduling of PDT-2 can be performed once at the earliest possibility after resolution, but rescheduling should not exceed 2 weeks.

Primary outcomes:
measure: Overall subject complete response rate
timeFrame: 12 weeks after the last PDT (Visit 4 or Visit 6)
Secondary outcomes:
measure: Overall subject complete response rate for subjects with lesions treated on extremities
timeFrame: 12 weeks after the last PDT (Visit 4 or Visit 6)
measure: Overall subject complete response rate for subjects with lesions treated on neck/trunk
timeFrame: 12 weeks after the last PDT (Visit 4 or Visit 6)
measure: Lesion complete response rate
timeFrame: 12 weeks after the last PDT (Visit 4 or Visit 6)
measure: Complete response rate for severe lesions
timeFrame: 12 weeks after the last PDT (Visit 4 or Visit 6)
measure: Subject complete response rate after PDT-1
timeFrame: 12 weeks after PDT-1 (Visit 4)
measure: Lesion complete response rate after PDT-1
timeFrame: 12 weeks after PDT-1 (Visit 4)
measure: Complete response rate for severe lesions after PDT-1
timeFrame: 12 weeks after PDT-1 (Visit 4)
measure: Esthetic appearance at the end of treatment phase assessed by the investigator
timeFrame: On final visit of the treatment phase, 12 weeks after the last PDT (Visit 4 or Visit 6)
measure: Esthetic outcome at the end of treatment phase assessed by the subject
timeFrame: On final visit of the treatment phase, 12 weeks after the last PDT (Visit 4 or Visit 6)
measure: Satisfaction with PDT at the end of treatment phase
timeFrame: On final visit of the treatment phase, 12 weeks after the last PDT (Visit 4 or Visit 6)
measure: Frequency and extent of adverse events (AEs), AEs of Special Interest (AESIs), serious AEs (SAEs) and treatment-emergent AEs (TEAEs) during treatment phase
timeFrame: Entire study duration, approx. 16 weeks for subjects requiring 1 PDT (until Visit 4) and approx. 28 weeks for subjects with 2 PDTs (until Visit 6)
measure: New lesions inside the treatment field during treatment phase
timeFrame: All clinical visits throughout entire study duration, approx. 16 weeks for subjects requiring 1 PDT (until Visit 4) and approx. 28 weeks for subjects with 2 PDTs (until Visit 6)
measure: Assessment of application site reactions
timeFrame: All visits (except screening, Visit 1) throughout entire study duration, approx. 16 weeks for subjects requiring 1 PDT (until Visit 4) and approx. 28 weeks for subjects with 2 PDTs (until Visit 6)
measure: Application site pain during illumination
timeFrame: During treatment (illumination) on treatment day for PDT-1 (Visit 2, up to 4 weeks after screening) and during treatment (illumination) on treatment day for PDT-2 (Visit 4; if applicable; 12 weeks after PDT-1)
measure: Number of patients with significant changes of vital signs
timeFrame: All clinical visits throughout entire study duration, approx. 16 weeks for subjects requiring 1 PDT (until Visit 4) and approx. 28 weeks for subjects with 2 PDTs (until Visit 6)
measure: Number of patients with significant changes in safety laboratory
timeFrame: All clinical visits throughout entire study duration, approx. 16 weeks for subjects requiring 1 PDT (until Visit 4) and approx. 28 weeks for subjects with 2 PDTs (until Visit 6)
measure: Number of patients with abnormal findings in physical examination
timeFrame: At screening (up to 4 weeks before treatment) and 12 weeks after the last PDT (Visit 4 or Visit 6)
Other outcomes:
measure: Subject recurrence rate
timeFrame: On follow-up Visit 1 (6 months after last PDT) and follow-up Visit 2 (12 months after last PDT)
measure: Lesion recurrence rate
timeFrame: On follow-up Visit 1 (6 months after last PDT) and follow-up Visit 2 (12 months after last PDT)
measure: Recurrence rate of severe lesions
timeFrame: On follow-up Visit 1 (6 months after last PDT) and follow-up Visit 2 (12 months after last PDT)
measure: Esthetic appearance at follow-up visits assessed by the investigator
timeFrame: On follow-up Visit 1 (6 months after last PDT) and follow-up Visit 2 (12 months after last PDT)
measure: Esthetic outcome at follow-up visits assessed by the subject
timeFrame: On follow-up Visit 1 (6 months after last PDT) and follow-up Visit 2 (12 months after last PDT)
measure: Satisfaction with PDT at follow-up visits
timeFrame: On follow-up Visit 1 (6 months after last PDT) and follow-up Visit 2 (12 months after last PDT)
measure: Any SAE and relevant AE
timeFrame: Entire follow-up duration, approx. 40 weeks
measure: New lesions inside the treatment field during follow-up
timeFrame: On follow-up Visit 1 (6 months after last PDT) and follow-up Visit 2 (12 months after last PDT)
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: Delray Beach
country: United States
facility: Dermatology Associates PA of the Palm Beaches
state: Florida
city: Snellville
country: United States
facility: Gwinnett Clinical Research Center, Inc.
state: Georgia
city: Indianapolis
country: United States
facility: Laser and Skin Surgery Center of Indiana
state: Indiana
city: Plainfield
country: United States
facility: The Indiana Clinical Trials Center, PC
state: Indiana
city: Baton Rouge
country: United States
facility: DelRicht Research
state: Louisiana
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: Austin
country: United States
facility: DermResearch, P.A.
state: Texas
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: Medical Dermatology Specialists; Phoenix, Arizona, United States
name: Nathalie Zeitouni, MD
role: PRINCIPAL_INVESTIGATOR
References: