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
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1h incubation BF-200 ALA Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid) red light photodynamic therapy (PDT) utilizing BF-RhodoLED® after 1h incubation. |
Combination Product: 1h Incubation Photodynamic therapy (PDT) (ALA-PDT, Ameluz®-PDT)
Facial acne lesions will be cleansed with gauze soaked with ethanol or isopropanol. Afterwards, approximately 1 tube of study medication will be applied as a thin layer to the whole face. After drug application, subjects should stay inside for 1 hour. Post incubation, red light illumination with BF-RhodoLED® will be performed according to the lamps user manual until a total light energy of 37 J/cm2 was applied. To cover the whole face 2 illuminations will be required which can either be performed subsequentially or in parallel (with 2 lamps).
Other Names:
ALA-PDT, Ameluz®-PDT
|
| Experimental: 3h incubation BF-200 ALA Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid) red light photodynamic therapy (PDT) utilizing BF-RhodoLED® after 3h incubation. |
Combination Product: 3h Incubation Photodynamic therapy (PDT) (ALA-PDT, Ameluz®-PDT)
Facial acne lesions will be cleansed with gauze soaked with ethanol or isopropanol. Afterwards, approximately 1 tube of study medication will be applied as a thin layer to the whole face. After drug application, subjects should stay inside for 3 hours. Post incubation, red light illumination with BF-RhodoLED® will be performed according to the lamps user manual until a total light energy of 37 J/cm2 was applied. To cover the whole face 2 illuminations will be required which can either be performed subsequentially or in parallel (with 2 lamps).
Other Names:
ALA-PDT, Ameluz®-PDT
|
| Placebo Comparator: 1h incubation vehicle Topical application of vehicle to BF-200 ALA red light photodynamic therapy (PDT) utilizing BF-RhodoLED® after 1h incubation. |
Combination Product: 1h Incubation Photodynamic therapy (PDT) (vehicle to BF-200 ALA containing no active ingredient)
Facial acne lesions will be cleansed with gauze soaked with ethanol or isopropanol. Afterwards, approximately 1 tube of study medication will be applied as a thin layer to the whole face. After drug application, subjects should stay inside for 1h. Post incubation, red light illumination with BF-RhodoLED® will be performed according to the lamps user manual until a total light energy of 37 J/cm2 was applied. To cover the whole face 2 illuminations will be required which can either be performed subsequentially or in parallel (with 2 lamps).
|
| Placebo Comparator: 3h incubation vehicle Topical application of vehicle to BF-200 ALA red light photodynamic therapy (PDT) utilizing BF-RhodoLED® after 3h incubation. |
Combination Product: 3h Incubation Photodynamic therapy (PDT) (vehicle to BF-200 ALA containing no active ingredient)
Facial acne lesions will be cleansed with gauze soaked with ethanol or isopropanol. Afterwards, approximately 1 tube of study medication will be applied as a thin layer to the whole face. After drug application, subjects should stay inside for 3h. Post incubation, red light illumination with BF-RhodoLED® will be performed according to the lamps user manual until a total light energy of 37 J/cm2 was applied. To cover the whole face 2 illuminations will be required which can either be performed subsequentially or in parallel (with 2 lamps).
|
Outcome Measures
Primary Outcome Measures
- Absolute change in the number of inflammatory lesions (absolute change from baseline) 8 weeks after the last PDT as assessed by investigator. [8 weeks after the last PDT]
Outcome 1 is the absolute change in the number of inflammatory lesions at the final visit with respect to baseline as assessed by the investigator.
- 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 at an mIGA score of 0 (clear) or 1 (almost clear). [8 weeks after the last PDT]
Treatment success is defined as a minimum improvement of the mIGA score by at least 2 and resulting at an mIGA score of 0 (clear) or 1 (almost clear).
Secondary Outcome Measures
- Relative change in the number of inflammatory lesions (percentage change from baseline) 8 weeks after the last PDT as assessed by investigator. [8 weeks after the last PDT]
Outcome 3 is the percentage change of inflammatory lesions from baseline as assessed by the investigator.
- Relative change in the number of inflammatory lesions (percentage change from baseline) 8 weeks after the last PDT as assessed by the Canfield algorithm. [8 weeks after the last PDT]
Outcome 4 is the percentage change of inflammatory lesions from baseline as assessed by an automated lesions count based on pictures taken by Canfields Visia-CR system
- Change in the number of inflammatory and/or non-inflammatory lesions (absolute change and/or percentage change from baseline) as assessed by investigator. [4 or 8 weeks after the last PDT]
In particular, the following will be assessed: Inflammatory lesions - 4 weeks after the last PDT Non-inflammatory lesions - 4 weeks after the last PDT Non-inflammatory lesions - 8 weeks after the last PDT Inflammatory & non-inflammatory lesions - 4 weeks after the last PDT Inflammatory & non-inflammatory lesions - 8 weeks after the last PDT
- Change in the number of inflammatory and/or non-inflammatory lesions (absolute change and/or percentage change from baseline) as assessed by the Canfield algorithm [8 weeks after the last PDT]
In particular, the following will be assessed: Inflammatory lesions - 8 weeks after the last PDT Non-inflammatory lesions - 8 weeks after the last PDT Inflammatory & non-inflammatory lesions - 8 weeks after the last PDT
- Change in the number of inflammatory and/or non-inflammatory lesions for subjects with no remaining inflammatory lesions (subjects receiving only 1 PDT; absolute change and percentage change from baseline) as assessed by investigator. [4 or 8 weeks after the 1st PDT]
In particular, the following will be assessed: Inflammatory lesions - 4 weeks after the 1st PDT Inflammatory lesions - 8 weeks after the 1st PDT Non-Inflammatory lesions - 4 weeks after the 1st PDT Non-Inflammatory lesions - 8 weeks after the 1st PDT Inflammatory & non-inflammatory lesions - 4 weeks after the 1st PDT Inflammatory & non-inflammatory lesions - 8 weeks after the 1st PDT
- Change in the number of inflammatory and/or non-inflammatory lesions for subjects with no remaining inflammatory lesions (subjects receiving 2 PDTs; absolute change and percentage change from baseline) as assessed by investigator. [4 or 8 weeks after the 2nd PDT]
In particular, the following will be assessed: Inflammatory lesions - 4 weeks after the 2nd PDT Inflammatory lesions - 8 weeks after the 2nd PDT Non-Inflammatory lesions - 4 weeks after the 2nd PDT Non-Inflammatory lesions - 8 weeks after the 2nd PDT Inflammatory & non-inflammatory lesions - 4 weeks after the 2nd PDT Inflammatory & non-inflammatory lesions - 8 weeks after the 2nd PDT
- Change in the number of inflammatory and/or non-inflammatory lesions for subjects with no remaining inflammatory lesions (subjects receiving 3 PDTs; absolute change and percentage change from baseline) as assessed by investigator. [4 or 8 weeks after the 3rd PDT]
In particular, the following be assessed: Inflammatory lesions - 4 weeks after the 3rd PDT Inflammatory lesions - 8 weeks after the 3rd PDT Non-Inflammatory lesions - 4 weeks after the 3rd PDT Non-Inflammatory lesions - 8 weeks after the 3rd PDT Inflammatory & non-inflammatory lesions - 4 weeks after the 3rd PDT Inflammatory & non-inflammatory lesions - 8 weeks after the 3rd PDT
- Treatment success defined by a minimum improvement of the PAS and mPAS equivalent to an improvement of IGA and mIGA by at least 2, assessed by the Canfield algorithm [8 weeks after the last PDT]
In particular, the following will be assessed: a. Across all subjects, irrespective of the final parametric acne score (PAS) and modified PAS (mPAS) PAS/mPAS are equivalent to the IGA/mIGA but results from the automated assessment of acne severity based on pictured taken with the canfield system
- Improvement of scar severity and overall esthetic appearance. [8 weeks after last PDT]
As assessed by the investigator via a physical global scale for acne scars (PGA)
- Improvement of texture as assessed by Canfield algorithm. [8 weeks after last PDT]
Based on pictures taken during the study visits. Pictures will be analyzed with respect to areas of facial roughness and raised topography of acne lesions.
- Satisfaction regarding esthetic outcome and treatment. [8 weeks after the last PDT.]
As reported by the subject.
Other Outcome Measures
- Frequency and severity of adverse events (AEs), serious AEs (SAEs), and treatment-emergent adverse events (TEAEs). TEAE are defined as all AEs with onset or worsening after first treatment with IMP up to the last visit of the subject. [from screening to study completion, over a duration of up to approximately 25 weeks]
TEAEs are defined as all AEs with onset or worsening after first treatment with IMP up to the last visit of the subject (approximately 8 weeks post last PDT).
- Application site skin reactions assessed by the investigator. [from screening to study completion, over a duration of up to approximately 25 weeks]
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 reported by the subjects. [from screening to study completion, over a duration of up to approximately 25 weeks]
pplication site discomfort categories: burning, hyperaesthesia, pain, paraesthesia, pruritus, stinging, warmth, other; severity of AE: mild, moderate or severe
- Pain during illumination reported by the subject. [from screening to study completion, over a duration of up to approximately 25 weeks]
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".
- Changes in blood pressure [at all clinic visits conducted over a duration of approximately 25 weeks]
systolic & diastolic [mmHg]
- Changes in heart rate [at all clinic visits conducted over a duration of approximately 25 weeks]
[bpm]
- Investigation of clinical chemistry parameters [first and last visit conducted up to approximately 25 weeks apart]
Findings which differ from reference range and are considered to be clinically significant are to be reported.
- Investigation of hematology parameters [first and last visit conducted up to approximately 25 weeks apart]
Findings which differ from reference range and are considered to be clinically significant are to be reported.
- Investigation of urinalysis parameters [first and last visit conducted up to approximately 25 weeks apart]
Findings which differ from reference range and are considered to be clinically significant 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 [first and last visit conducted up to approximately 25 weeks apart]
Abnormal findings, considered to be clinically significant, are to be reported.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
-
Subjects with moderate to severe acne on the face (IGA ≥3, PAS ≥0.5).
-
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. The investigator's lesion count should be confirmed by the automated lesion count via the Canfield algorithm (cutoff for Canfield is a number that is at maximum 20% below the investigator's assessment). As per investigator's assessment, the number of nodules and cysts should not exceed 5% of all inflammatory lesions.
-
All sexes, ≥16 years of age.
-
Willingness and ability to comply with study procedures, particularly willingness to receive up to 3 PDTs within 8 to 10 weeks.
-
Subjects with good general health or with clinically stable medical conditions will be permitted to be included in the study.
-
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).
-
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:
-
Any known history of hypersensitivity to ALA, porphyrins or excipients of BF-200 ALA.
-
History of soy or peanut allergy.
-
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.)
-
Clinical diagnosis of atopic dermatitis and other cutaneous conditions (e.g. lupus erythematosis), Bowen's disease, BCC, eczema, psoriasis, acne conglobata, acne fulminans, or secondary acne (steroid-induced acne, perioral dermatitis, acne rosacea), squamous cell carcinoma, other malignant or benign tumors in the treatment field.
-
Clinically significant (CS) medical conditions making implementation of the protocol or interpretation of the study results difficult or impairing subject's safety such as:
-
Presence of photodermatoses or porphyria
-
Metastatic tumor or tumor with high probability of metastasis
-
Infiltrating skin neoplasia (suspected or known)
-
Unstable cardiovascular disease (New York Heart Association class III, IV)
-
Unstable hematologic (including Myelodysplastic syndrome), hepatic, renal, neurologic, or endocrine condition
-
Unstable collagen-vascular condition
-
Unstable gastrointestinal condition
-
Immunosuppressive condition
-
Presence of clinically significant inherited or acquired coagulation defect
-
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).
-
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).
-
Presence of strong artificial pigmentation (e.g. tattoos) or any other abnormality that may impact lesion assessment or light penetration in the treatment field.
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Suspicion of drug or alcohol abuse.
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Any topical medication of the skin prior to screening as defined below:
-
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.
-
Topical treatment with immunosuppressive, cytostatic or cytotoxic drugsinside the treatment field within 8 weeks prior to screening.
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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 applied for more than 4 weeks prior to screening visit without evidence of an actual phototoxic/photoallergic reaction.
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Any use of the below specified systemic treatments within the designated periods:
-
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).
-
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.
-
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 screened and randomized if such medication wastaken in or applied for more than 8 weeks prior to screening visit without evidence of an actual phototoxic/photoallergic reaction.
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Breast feeding women.
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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.
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Prior randomization in the study.
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A member of study site staff or sponsor staff directly involved in the conduct of the protocol or a close relative thereof.
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Simultaneous participation in a further clinical study.
Dosing Day exclusion criteria:
-
Febrile or infectious disease within 7 days prior to PDT visits.
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Subjects with sunburn, wounds, irritations, bleeding or other confounding skin conditions within illumination areas at PDT visits.
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Application of topical glycocorticosteroids in- and outside the treatment field within 7 days prior to PDT visits
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | First OC Dermatology | Fountain Valley | California | United States | 92708 |
| 2 | Cosmetic Laser Dermatology | San Diego | California | United States | 92121 |
| 3 | Dermatology Associates PA of the Palm Beaches | Delray Beach | Florida | United States | 33445 |
| 4 | Skin Search of Rochester, Inc | Rochester | New York | United States | 14623 |
| 5 | Clinical Research Center of the Carolinas | Charleston | South Carolina | United States | 29407 |
| 6 | Austin Institute for Clinical Research Inc. | Pflugerville | Texas | United States | 78660 |
Sponsors and Collaborators
- Biofrontera Bioscience GmbH
Investigators
- Principal Investigator: Mitchel P Goldman, MD, Dermatology Cosmetic Laser Medical Associates of La Jolla, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ALA-ACV-CT014