Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as BF-200 ALA gel, BF-200 ALA
BF-200 ALA and red light LED lamp · 7 trials · 5 indications
Percentage of subjects with all AK target lesions clinically cleared after last PDT
Overall patient complete response rate assessed 12 weeks after the last PDT. The indicated values give the percentage of overall complete responders. An overall complete responder is defined as a patient in whom all treated lesions were cleared. The PP set is the primary analysis set for the analyses of the primary endpoint.
All efficacy variables were evaluated for the FAS. The primary efficacy variable was also analyzed for the PP population. All subgroup analyses were carried out for the FAS. Data for size and grade of AK lesions were analyzed using the last observation carried forward (LOCF) approach, affecting the response rates evaluation. Due to the small amount of missing data in the study, which did not have any relevant impact on primary results, sensitivity analyses for missing data were not performed. The primary efficacy variable was the overall patient complete response 12 weeks after the last PDT. An overall complete responder was defined as a patient in whom all treated actinic keratosis (AK) lesions were cleared (Olsen score of 0) after the last PDT, i.e. after PDT 1 or after PDT 2 if re-treatment was performed.
All efficacy variables were evaluated for the FAS. The primary efficacy variable was also analyzed for the PP population. All subgroup analyses were carried out for the FAS. Data for size and grade of AK lesions were analyzed using the last observation carried forward (LOCF) approach, affecting the response rates evaluation. Due to the small amount of missing data in the study, which did not have any relevant impact on primary results, sensitivity analyses for missing data were not performed. The primary efficacy variable was the overall patient complete response 12 weeks after the last PDT. An overall complete responder was defined as a patient in whom all treated AK lesions were cleared (Olsen score of 0) after the last PDT, i.e. after PDT 1 or after PDT 2 if re-treatment was performed.
An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT. The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)
An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT. The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)
Subgroup analysis of patients treated with a narrow spectrum device for PDT Illumination (\~630 nm). An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT. The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)
AK clearance rate, defined as the percentage of subjects with complete remission of all AK lesions in the target area(s) assessed 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment).
AK clearance rate, defined as the percentage of subjects with complete remission of all AK lesions in the target area(s) assessed 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). Analysis was for the subgroup: treated by narrow spectrum lamps only \[n=15 (vehicle), n= 31 (BF-200 ALA)\]
TEAEs are defined as all AEs with onset or worsening after treatment with IMP up to Visit 5 (Final Visit). TEAEs are considered being related to IMP or medical device, if causal relationship between IMP or medical device and the TEAE is at least possible or relationship assessment is missing. If an AE occurs in different treatment areas (face, scalp, face and scalp), it is reported separately for each treatment area. Thus, some AEs are counted more than once.
The duration of TEAEs related to IMP and/or medical device which occurred in at least two subjects and with complete start and stop dates was analyzed. In addition, the proportion of the duration by severity was analyzed. Duration of severity per subject and preferred term is calculated in days counting all days and all episodes of one severity category together. Calculation is done referring to all subjects with occurrence of respective preferred term. If a severity category of a preferred term does not occur in a subject, the duration of this category is set to 0. If an AE occurs in different treatment areas, it is reported separately for each treatment area (face, scalp, face and scalp). Thus, some AEs are counted more than once for the analysis.
Assessed were newly occuring lesions of actinic keratosis (AK), non-melanoma skin cancer (NMSC) such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or Bowens disease, and melanoma inside the treatment field. Cumulative number of lesions is reported.
Assessed were newly occuring lesions of actinic keratosis (AK), non-melanoma skin cancer (NMSC) such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or Bowens disease, and melanoma inside the treatment field. Cumulative number of lesions is reported.
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 categories: burning, hyperaesthesia, pain, paraesthesia, pruritus, stinging, warmth, other; severity of AE: mild, moderate or severe
Assessed by the subjects using an 11-point numeric rating scale (NRS), where a score of 0 means "no pain" and a score of 10 means "worst imaginable pain".
Change from baseline is presented. The first measurement at Visit 2 (arrival at site) was considered as baseline value for all following measurements. Blood pressure was measured in mmHg. At Visit 2, photodynamic therapy was performed.
Change from baseline is presented. The first measurement at Visit 2 (arrival at the site) was considered as baseline value for all following measurements. Pulse rate was measures in beats/min. At Visit 2, photodynamic therapy was performed.
Change from baseline is presented. The first measurement at Visit 2 (arrival at site) was considered as baseline value for all following measurements. Body temperature was measured in °F and was converted to °C in the electronic Case Report Form. At Visit 2, photodynamic therapy was performed.
Findings which differ from reference range and are considered to be clinically significant are to be reported. Clinical chemistry parameters include glucose, creatinine, total bilirubin, aspartate aminotransferase (AST), alanineaminotransferase (ALT), lactate dehydrogenase (LDH), alkalinephosphatase (AP),gamma glutamyl transferase (GGT), potassium, sodium, calcium, total protein, albumin.
Findings which differ from reference range and are considered to be clinically significant are to be reported. Hematology parameters include hemoglobin, hematocrit, red blood cell count, leukocyte count (white blood cells(WBC)) with differential count (neutrophils, lymphocytes, monocytes, eosinophils, basophils), and platelet count.
Findings which differ from reference range and are considered to be clinically significant (CS) are to be reported
Abnormal findings, considered to be clinically significant (CS), are to be reported
Including picture- and question-based memory tasks; abnormal findings that are considered clinically significant will be documented
Including investigation of pupils (equality), coordination (finger-nose test), gait (balance), and sensitivity (cheeks, arms, legs); abnormal findings that are considered clinically significant (CS) will be documented
Blood samples for ALA analysis for each subject were collected, starting at Visit 1 and then 0.5h prior to BF-200 ALA application for up to 10h afterwards. The concentrations of ALA in plasma were measured by an analytical laboratory using validated, internally standardized liquid chromatography-tandem mass spectrometry methods.
Blood samples for PpIX analysis for each subject were collected, starting at Visit 1 and then 0.5h prior to BF-200 ALA application for up to 10h afterwards. The concentrations of PpIX in plasma were measured by an analytical laboratory using validated, internally standardized liquid chromatography-tandem mass spectrometry methods.
| Arm | Type | Description |
|---|---|---|
| BF-200 ALA | EXPERIMENTAL | Topical application of BF-200 ALA containing 10% 5-ALA HCl (5-aminolevulinic acid hydrochloride). Red light photodynamic therapy (PDT) |
| Vehicle | PLACEBO_COMPARATOR | Topical application of vehicle to BF-200 ALA containing no active ingredient. Red light photodynamic therapy (PDT) |
| methyl-aminolevulinate | ACTIVE_COMPARATOR | Topical application of Metvix creme containing 160 mg/g methyl-aminolevulinate. Application of a 1 mm thick layer covering each lesion and 0.5 to 1 cm of surrounding margin. |
| BF-200 ALA gel | ACTIVE_COMPARATOR | Photodynamic therapy with BF-RhodoLED in combination with BF-200 ALA. |
| Placebo to BF-200 ALA gel | PLACEBO_COMPARATOR | Photodynamic therapy with BF-RhodoLED in combination with a nanoemulsion gel formulation similar to BF-200 ALA, but without the active ingredient 5-aminolevulinic acid. |
| MAL Cream | ACTIVE_COMPARATOR | Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. |
| Name | Type | Description |
|---|---|---|
| BF-200 ALA and red light LED lamp | COMBINATION_PRODUCT | Up to two PDTs using a RhodoLED lamp (RhodoLED® XL or BF-RhodoLED®) (ALA-PDT, Ameluz®-PDT): Topical application of up to 3 tubes BF-200 ALA on the expanded treatment field (up to 240 cm²), followed by red light illumination with a RhodoLED lamp after 3 h incubation of study medication under occlusive dressing. PDT-1 will be performed at Visit 2. Clinical clearance will be assessed 12 weeks after PDT-1 (Visit 4). In case of remaining lesions at Visit 4, PDT-2 will be performed at the same visit. |
| Vehicle and red light LED lamp | COMBINATION_PRODUCT | Up to two PDTs using a RhodoLED lamp (RhodoLED® XL or BF-RhodoLED®) (Vehicle-PDT): Topical application of up to 3 tubes vehicle on the expanded treatment field (up to 240 cm²), followed by red light illumination with a RhodoLED lamp after 3 h incubation of study medication under occlusive dressing. PDT-1 will be performed at Visit 2. Clinical clearance will be assessed 12 weeks after PDT-1 (Visit 4). In case of remaining lesions at Visit 4, PDT-2 will be performed at the same visit. |
| BF-200 ALA | DRUG | Topical treatment for photodynamic therapy combining drug application and subsequent illumination with a narrow spectrum light source (after 3 h of drug incubation) |
| methyl-aminolevulinate | DRUG | Topical treatment for photodynamic therapy combining drug application and subsequent illumination with a narrow spectrum light source (after 3 h of drug incubation) |
| BF-200 ALA gel | DRUG | BF-200 ALA was applied over 1-2 fields of approximately 20 cm² in total, allowed to dry for approximately 10 minutes, and covered with occlusive tape material for 3 h. |
| Placebo to BF-200 ALA gel | DRUG | The reference product was a placebo (a nanoemulsion gel formulation similar to the Investigational Medicinal Product (IMP), but without the active ingredient). The placebo was packaged, assigned to each patient, and administered in the same way as the IMP. |
| Photodynamic therapy with BF-RhodoLED | PROCEDURE | After cleaning the lesions, the entire treatment field(s) were illuminated using the novel narrow spectrum BF-RhodoLED lamp, a red light illumination source (approximately 635 nm) developed by Biofrontera, until a total light dose of 37 J/cm² (per treated field) was achieved. |
| MAL Cream | DRUG | topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source. |
| Vehicle | DRUG | topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source. |
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 t...
BF-200 ALA is used with photodynamic therapy, delivered using a red light LED lamp, to treat actinic keratoses, a common skin condition caused by sun damage. It is also being studied in basal cell carcinoma. Treatment is field-directed, meaning it covers broader areas of skin rather than single lesions.
BF-200 ALA is developed by Biofrontera Inc., which trades on the Nasdaq under the ticker BFRI. The company is a dermatology-focused biopharmaceutical developer. BF-200 ALA is administered together with a red light LED lamp as part of photodynamic therapy.
BF-200 ALA is in Phase 3 clinical development. It is an investigational product and is not described as FDA approved. Four trials have been completed, including two Phase 3 studies and two Phase 1 studies, with no active trials currently listed.
Completed trials include NCT05662202, a Phase 3 study of field-directed treatment of actinic keratosis on the extremities and neck or trunk; NCT02799082, a Phase 3 efficacy and safety study in actinic keratosis; and two Phase 1 studies, NCT05060237 and NCT04319159, evaluating safety in expanded fields of actinic keratosis.
Yes. BF-200 ALA is also known as BF-200 ALA gel and is marketed under the name Ameluz. These names refer to the same product, which is used with photodynamic therapy and a red light LED lamp for the treatment of actinic keratoses.
Across four completed clinical trials, 892 patients were enrolled in total. The studies were randomized, double-blind, and placebo-controlled. Enrollment ranged from 48 patients in a Phase 1 safety study to 172 patients in a Phase 3 study of actinic keratosis on the extremities and neck or trunk.