Clinical trial NCT05080764: Study to Evaluate the Safety and Efficacy of BF-200 ALA (Ameluz®) and BF-RhodoLED® in the Treatment of Moderate to Severe Acne Vulgaris With Photodynamic Therapy in Adults
Official title: A Randomized, Double Blind, Vehicle-controlled, Multicenter Phase II Study to Evaluate the Safety and Efficacy of BF-200 ALA (Ameluz®) and BF-RhodoLED® in the Treatment of Moderate to Severe Acne Vulgaris in Adults With Photodynamic Therapy (PDT)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Acne Vulgaris
Keywords: ALA-PDT
Lead sponsor: Biofrontera Bioscience GmbH
Sponsor class: INDUSTRY
First posted: 2021-10-18
Enrollment: 126
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
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 and efficacy of photodynamic therapy (PDT) for the medication Ameluz® performed with the PDT-lamp BF-RhodoLED® in comparison to the respective placebo treatment for moderate to severe Acne vulgaris.


Eligibility criteria: Inclusion Criteria:

1. Willingness and ability of the subject to provide informed consent and to 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. Minors under 18 years of age must be accompanied by the parent(s) or legal guardian(s) at the time of consent signing. The parent(s) or legal guardian(s) must also provide informed consent/HIPAA for the subject.
2. Subjects with moderate to severe acne on the face (IGA ≥3).
3. Presence of ≥20 inflammatory and ≥20 non-inflammatory (open and closed comedones) Acne vulgaris lesions on the face (should be located within not more than 2 illumination areas) as assessed by investigator.
4. All sexes, ≥16 years of age.
5. Willingness and ability to comply with study procedures, particularly willingness to receive up to 3 PDTs within 8 to 10 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 topical facial treatments other than medical cleansers (i.e. face washes etc.) at least 14 days prior to randomization visit (Visit 2, baseline) and discontinue medical cleansers in the face at least 1 week prior to randomization visit (Visit 2, baseline) and thereafter until the end of study (use of soap is allowed but the product used should not be changed during the study).
8. Females of reproductive potential must have a negative serum pregnancy test and must use an adequate and highly effective or two effective methods of contraception throughout the study. (If hormonal contraception is used, the same product and dose should be taken for at least 6 months before the first treatment and throughout the entire 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) within or in close proximity (\< 5 cm distance) to treatment field. (Reassessment of subjects is allowed once if the sunburn or other confounding skin conditions is/are expected to resolve within the screening period.

   Reassessment can be done on the day of the actual treatment.)
4. Clinical diagnosis of atopic dermatitis and other cutaneous conditions (e.g. lupus erythematosus), Bowen's disease, BCC, eczema, psoriasis, acne conglobate, acne fulminans, or secondary acne (steroid-induced acne, perioral dermatitis, acne rosacea), squamous cell carcinoma, other malignant or benign tumors in the treatment field.
5. 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
6. Beard or other facial hair that might interfere with the study assessments unless subject agrees to be clean-shaven throughout the entire study period. (Reassessment of subjects is allowed once if assessment of acne lesions is impaired by facial hair at screening. Reassessment can be performed on the day of the actual treatment).
7. Facial procedures such as dermabrasion, chemical or laser peels as well as exposure to UV radiation (other than sunlight) at least 4 weeks prior to randomization visit (Visit 2, baseline).
8. Presence of strong artificial pigmentation (e.g. tattoos) or any other abnormality that may impact lesion assessment or light penetration in the treatment field.
9. Suspicion of drug or alcohol abuse.
10. Any topical medication of the skin prior to screening as defined below:

    1. Topical treatment with ALA or ALA-esters (e.g. MAL) or an investigational drug in- and outside the treatment field within 8 weeks prior to screening.
    2. Topical treatment with immunosuppressive, cytostatic or cytotoxic drugs inside the treatment field within 8 weeks prior to screening.
    3. Start of a regular and continuous topical administration of medication with hypericin or other drugs with phototoxic or photoallergic potential inside the treatment field within 4 weeks prior to screening. Subjects may, however, be eligible if such medication was regularly applied for more than 4 weeks prior to screening visit without evidence of an actual phototoxic/photoallergic reaction or if such medication is only administered for a limited time (e.g. an antibiotic)
11. Any use of the below specified systemic treatments within the designated periods:

    1. Systemic acne therapy (oral antibiotics within 8 weeks or oral isotretinoin within 6 months or start with hormonal therapy for acne within 6 months prior to Visit 2).
    2. Use of cytotoxic or cytostatic drugs within 6 months, or immunosuppressive therapies or use of ALA or ALA-esters (e.g. MAL) within 12 weeks, investigational drugs or drugs known to have major organ toxicity within 8 weeks, interferon or glycocorticosteroids (oral or injectable) within 6 weeks prior to screening.
    3. Start of long-term intake of medication with hypericin or systemically acting drugs with phototoxic or photoallergic potential within 8 weeks prior to screening. Subjects may, however, be screened and randomized if such medication was taken in or was regularly applied for more than 8 weeks prior to screening visit without evidence of an actual phototoxic/photoallergic reaction or if such a drug is only used for a limited time (e.g. an antibiotic).
12. Breast feeding women.
13. Subject 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.
14. Prior randomization in the study.
15. A member of study site staff or sponsor staff directly involved in the conduct of the protocol or a close relative thereof.
16. Simultaneous participation in a further clinical study.
17. Four or more nodular acne lesions on the face.
18. Unwillingness or inability to limit sun exposure for 48 hours post PDT treatment.

Dosing Day exclusion criteria:

1. Febrile or infectious disease within 7 days prior to PDT visits.
2. Subjects with sunburn, wounds, irritations, bleeding or other confounding skin conditions within illumination areas at PDT visits.
3. Application of topical glycocorticosteroids in- and outside the treatment field within 7 days prior to PDT visits
4. Administration of (topical or systemic) medication with phototoxic/photoallergic potential for a limited time. After discontinuing the medication, a wash out period of the medications 5-fold half-life time should be applied prior to the next PDT.

Primary outcomes:
measure: Relative change in the number of inflammatory lesions (relative change from baseline) 8 weeks after the last PDT as assessed by investigator.
timeFrame: 8 weeks after the last PDT
measure: Treatment success defined by a minimum improvement of the modified investigator global assessment (mIGA) score by at least 2 assessed 8 weeks after the last PDT and resulting in an mIGA score of 0 (clear) or 1 (almost clear).
timeFrame: 8 weeks after the last PDT
Secondary outcomes:
measure: Absolute and/or percentage change from baseline in the number of lesions as assessed by investigator.
timeFrame: 4 or 8 weeks after the last PDT
measure: Absolute and percentage change from baseline in the number of lesions as assessed by investigator.
timeFrame: 4 or 8 weeks after the last PDT
measure: Absolute and percentage change from baseline in the number of lesions as assessed by investigator, only for responders at Visit 3 / 4 weeks after PDT-1.
timeFrame: 4 or 8 weeks after PDT-1
measure: Absolute and percentage change from baseline in the number of lesions as assessed by investigator, only for responders at Visit 4b / 4 weeks after PDT-2.
timeFrame: 4 or 8 weeks after PDT-2
measure: Absolute and percentage change in the number of lesions as assessed by investigator, only for responders at Visit 5b / 4 weeks after PDT-3.
timeFrame: 4 or 8 weeks after PDT-3
measure: Change in the number of nodules & cysts
timeFrame: 8 weeks after the last PDT
measure: Treatment success defined by a minimum improvement of the IGA by at least 2.
timeFrame: 8 weeks after the last PDT
measure: Improvement of the IGA.
timeFrame: 8 weeks after the last PDT
measure: Improvement of the mIGA.
timeFrame: 8 weeks after the last PDT
measure: Improvement of scar severity and overall esthetic appearance.
timeFrame: 8 weeks after last PDT
measure: Satisfaction regarding esthetic outcome and treatment.
timeFrame: 8 weeks after the last PDT.
Other outcomes:
measure: Frequency and severity of adverse events (AEs), serious AEs (SAEs), AEs of special interest (AESI) and treatment-emerged adverse events (TEAEs).
timeFrame: from screening to study completion, over a duration of up to approximately 25 weeks
measure: Application site skin reactions assessed by the investigator.
timeFrame: from screening to study completion, over a duration of up to approximately 25 weeks
measure: Application site discomfort reported by the subjects.
timeFrame: from screening to study completion, over a duration of up to approximately 25 weeks
measure: Pain during illumination reported by the subject.
timeFrame: from screening to study completion, over a duration of up to approximately 25 weeks
measure: Changes in blood pressure
timeFrame: at all clinic visits conducted over a duration of approximately 25 weeks
measure: Changes in heart rate
timeFrame: at all clinic visits conducted over a duration of approximately 25 weeks
measure: Investigation of clinical chemistry parameters
timeFrame: first and last visit conducted up to approximately 25 weeks apart
measure: Investigation of hematology parameters
timeFrame: first and last visit conducted up to approximately 25 weeks apart
measure: Investigation of urinalysis parameters
timeFrame: first and last visit conducted up to approximately 25 weeks apart
measure: Physical examination of head, neck, skin, lymph nodes, thorax including heart and lungs, abdomen, and musculoskeletal, peripheral vascular and nervous system status
timeFrame: first and last visit conducted up to approximately 25 weeks apart
Locations:
city: Fountain Valley
country: United States
facility: First OC Dermatology
state: California
city: San Diego
country: United States
facility: Cosmetic Laser Dermatology
state: California
city: Delray Beach
country: United States
facility: Dermatology Associates PA of the Palm Beaches
state: Florida
city: Tampa
country: United States
facility: ForCare Clinical Research
state: Florida
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: Charleston
country: United States
facility: Clinical Research Center of the Carolinas
state: South Carolina
city: Austin
country: United States
facility: DermResearch PA
state: Texas
city: Pflugerville
country: United States
facility: Austin Institute for Clinical Research Inc.
state: Texas
Study officials:
affiliation: Dermatology Cosmetic Laser Medical Associates of La Jolla, Inc.
name: Mitchel P Goldman, MD
role: PRINCIPAL_INVESTIGATOR
References: