Actinic Keratosis, Keratosis, Keratosis, Actinic
Conditions
Keywords
Actinic keratosis, Photodynamic therapy, 5-aminolevulinic acid, Photosensitizing Agents, Dermatologic Agents, Precancerous condition, Skin Disease
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.
Interventions
COMBINATION_PRODUCTBF-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.
Sponsors
Biofrontera Bioscience GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigation of Hematology Parameters | At screening (Visit 1, 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. 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. |
| Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Through study completion, on average 6 weeks | 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. |
| Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment) | 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. |
| Assessment of New Lesions (AK, NMSC Such as BCC, SCC or Bowens Disease, and Melanoma) if They Occur Inside the Treatment Field | From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment) | 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. |
| Assessment of New Lesions (AK, NMSC, and Melanoma) if They Occur Around the Treatment Field at a Distance of <10 cm | From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment) | 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 Reactions During and Post PDT, Assessed by the Investigator | From treatment day (day 1, Visit 2) 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 |
| Application Site Discomfort During and Post PDT, Reported by the Subjects | From treatment day (day 1, Visit 2) 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 |
| Application Site Pain During Illumination | At treatment day (day 1, Visit 2) after end of illumination | 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. |
| Changes in Blood Pressure (Systolic and Diastolic) | All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment | 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. |
| Changes in Pulse Rate | All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment | 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. |
| Changes in Body Temperature | All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment | 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. |
| Investigation of Clinical Chemistry Parameters | At screening (Visit 1, 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. 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. |
| Investigation of Urinalysis Parameters | At screening (Visit 1, 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 (CS) 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 | At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment) | Abnormal findings, considered to be clinically significant (CS), are to be reported |
| Memory Tests | At screening (Visit 1, 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 |
| Neurological Investigations | At screening (Visit 1, 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 (CS) will be documented |
Countries
United States
Participant flow
Pre-assignment details
According to protocol, 100 participants were planned to be dosed. To meet this requirement, 112 participants were enrolled, resulting in 100 participants to receive treatment.
Participants by arm
| Arm | Count |
|---|---|
| Face (BF-200 ALA) Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid).
One single photodynamic therapy (PDT).
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) on the face, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing. | 40 |
| Scalp (BF-200 ALA) Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid).
One single photodynamic therapy (PDT).
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) on the scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing. | 39 |
| Face and Scalp (BF-200 ALA) Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid).
One single photodynamic therapy (PDT).
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) on the face and scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing. | 21 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Screening failure | 8 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Face and Scalp (BF-200 ALA) | Total | Face (BF-200 ALA) | Scalp (BF-200 ALA) |
|---|---|---|---|---|
| Age, Continuous | 66.5 years STANDARD_DEVIATION 7.9 | 67.9 years STANDARD_DEVIATION 7.4 | 66.5 years STANDARD_DEVIATION 7.5 | 70.1 years STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 99 Participants | 40 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fitzpatrick skin type I-II | 14 Participants | 65 Participants | 31 Participants | 20 Participants |
| Fitzpatrick skin type III-IV | 7 Participants | 35 Participants | 9 Participants | 19 Participants |
| Number of AK lesions Diameter < 4 mm | 1.8 Number of AK lesions STANDARD_DEVIATION 3.9 | 3.7 Number of AK lesions STANDARD_DEVIATION 9.1 | 4.3 Number of AK lesions STANDARD_DEVIATION 9.9 | 4.1 Number of AK lesions STANDARD_DEVIATION 10.1 |
| Number of AK lesions Diameter ≥ 4 mm | 15.0 Number of AK lesions STANDARD_DEVIATION 11.4 | 13.0 Number of AK lesions STANDARD_DEVIATION 7.8 | 13.3 Number of AK lesions STANDARD_DEVIATION 7.9 | 11.6 Number of AK lesions STANDARD_DEVIATION 4.4 |
| Number of AK lesions Total | 16.8 Number of AK lesions STANDARD_DEVIATION 11.4 | 16.7 Number of AK lesions STANDARD_DEVIATION 11.1 | 17.6 Number of AK lesions STANDARD_DEVIATION 11 | 15.7 Number of AK lesions STANDARD_DEVIATION 11.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 99 Participants | 40 Participants | 39 Participants |
| Severity of AK target lesions ≥ 4 mm Mild/ grade 1 | 147 Number of AK lesions | 685 Number of AK lesions | 329 Number of AK lesions | 209 Number of AK lesions |
| Severity of AK target lesions ≥ 4 mm Moderate/ grade 2 | 165 Number of AK lesions | 599 Number of AK lesions | 203 Number of AK lesions | 231 Number of AK lesions |
| Severity of AK target lesions ≥ 4 mm Severe/ grade 3 | 3 Number of AK lesions | 15 Number of AK lesions | 0 Number of AK lesions | 12 Number of AK lesions |
| Sex: Female, Male Female | 0 Participants | 12 Participants | 12 Participants | 0 Participants |
| Sex: Female, Male Male | 21 Participants | 88 Participants | 28 Participants | 39 Participants |
| Total area of AK target lesions ≥ 4 mm | 626.8 mm ^2 STANDARD_DEVIATION 361 | 575.9 mm ^2 STANDARD_DEVIATION 579.3 | 426.5 mm ^2 STANDARD_DEVIATION 269.7 | 701.8 mm ^2 STANDARD_DEVIATION 830.6 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 100 |
| other Total, other adverse events | 100 / 100 |
| serious Total, serious adverse events | 0 / 100 |
Outcome results
Primary
Application Site Discomfort During and Post PDT, Reported by the Subjects
Application site discomfort categories: burning, hyperaesthesia, pain, paraesthesia, pruritus, stinging, warmth, other; severity of AE: mild, moderate or severe
Time frame: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total (BF-200 ALA) | Application Site Discomfort During and Post PDT, Reported by the Subjects | Application site hypoaesthesia | 1.0 percentage of participants |
| Total (BF-200 ALA) | Application Site Discomfort During and Post PDT, Reported by the Subjects | Application site pain | 96.0 percentage of participants |
| Total (BF-200 ALA) | Application Site Discomfort During and Post PDT, Reported by the Subjects | Any application site discomfort | 97.0 percentage of participants |
| Total (BF-200 ALA) | Application Site Discomfort During and Post PDT, Reported by the Subjects | Application site discomfort | 11.0 percentage of participants |
| Total (BF-200 ALA) | Application Site Discomfort During and Post PDT, Reported by the Subjects | Application site hyperaesthesia | 10.0 percentage of participants |
| Total (BF-200 ALA) | Application Site Discomfort During and Post PDT, Reported by the Subjects | Application site paraesthesia | 15.0 percentage of participants |
| Total (BF-200 ALA) | Application Site Discomfort During and Post PDT, Reported by the Subjects | Application site photosensitivity reaction | 1.0 percentage of participants |
| Total (BF-200 ALA) | Application Site Discomfort During and Post PDT, Reported by the Subjects | Application site pruritus | 65.0 percentage of participants |
| Total (BF-200 ALA) | Application Site Discomfort During and Post PDT, Reported by the Subjects | Application site warmth | 17.0 percentage of participants |
Primary
Application Site Pain During Illumination
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.
Time frame: At treatment day (day 1, Visit 2) after end of illumination
Population: For this study, concomitant medication as pain-relieving measure prior to illumination, concomitant medications given as pain-relieving measures during illumination and physical pain-relieving measures (i.e. interruption of the illumination and/or cooling with an air stream and/or nebulized water) were allowed. Subjects might have received a combination of medications (prior and/or during) and/or measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total (BF-200 ALA) | Application Site Pain During Illumination | With concomitant pain relieving medication during illumination | 8.4 score on a scale | Standard Deviation 1.9 |
| Total (BF-200 ALA) | Application Site Pain During Illumination | Overall | 7.4 score on a scale | Standard Deviation 2.1 |
| Total (BF-200 ALA) | Application Site Pain During Illumination | Without concomitant pain relieving medication prior to illumination | 7.6 score on a scale | Standard Deviation 1.8 |
| Total (BF-200 ALA) | Application Site Pain During Illumination | With concomitant pain relieving medication prior to illumination | 7.2 score on a scale | Standard Deviation 2.5 |
| Total (BF-200 ALA) | Application Site Pain During Illumination | Without concomitant pain relieving medication during illumination | 7.3 score on a scale | Standard Deviation 2.1 |
| Total (BF-200 ALA) | Application Site Pain During Illumination | Without physical pain relieving measures during illumination | 8.1 score on a scale | Standard Deviation 2 |
| Total (BF-200 ALA) | Application Site Pain During Illumination | With physical pain relieving measures during illumination | 7.3 score on a scale | Standard Deviation 2.2 |
Primary
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator
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
Time frame: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site erythema | 86.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Any application site skin reactions | 96.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site discharge | 4.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site discolouration | 6.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site dryness | 4.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site erosion | 16.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site exfoliation | 87.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site fissure | 1.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site haemorrhage | 10.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site induration | 18.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site oedema | 35.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site papules | 2.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site scab | 49.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site swelling | 6.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site vesicles | 14.0 percentage of partcipants |
| Total (BF-200 ALA) | Application Site Skin Reactions During and Post PDT, Assessed by the Investigator | Application site pustules | 3.0 percentage of partcipants |
Primary
Assessment of New Lesions (AK, NMSC, and Melanoma) if They Occur Around the Treatment Field at a Distance of <10 cm
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.
Time frame: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total (BF-200 ALA) | Assessment of New Lesions (AK, NMSC, and Melanoma) if They Occur Around the Treatment Field at a Distance of <10 cm | Any new lesions | 10 Number of lesions |
| Total (BF-200 ALA) | Assessment of New Lesions (AK, NMSC, and Melanoma) if They Occur Around the Treatment Field at a Distance of <10 cm | Seborrhoeic keratosis | 1 Number of lesions |
| Total (BF-200 ALA) | Assessment of New Lesions (AK, NMSC, and Melanoma) if They Occur Around the Treatment Field at a Distance of <10 cm | Squamous cell carcinoma | 1 Number of lesions |
| Total (BF-200 ALA) | Assessment of New Lesions (AK, NMSC, and Melanoma) if They Occur Around the Treatment Field at a Distance of <10 cm | Actinic keratosis | 8 Number of lesions |
Primary
Assessment of New Lesions (AK, NMSC Such as BCC, SCC or Bowens Disease, and Melanoma) if They Occur Inside the Treatment Field
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.
Time frame: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total (BF-200 ALA) | Assessment of New Lesions (AK, NMSC Such as BCC, SCC or Bowens Disease, and Melanoma) if They Occur Inside the Treatment Field | Any new lesions | 38 Number of lesions |
| Total (BF-200 ALA) | Assessment of New Lesions (AK, NMSC Such as BCC, SCC or Bowens Disease, and Melanoma) if They Occur Inside the Treatment Field | Milia | 1 Number of lesions |
| Total (BF-200 ALA) | Assessment of New Lesions (AK, NMSC Such as BCC, SCC or Bowens Disease, and Melanoma) if They Occur Inside the Treatment Field | Seborrhoeic keratosis | 1 Number of lesions |
| Total (BF-200 ALA) | Assessment of New Lesions (AK, NMSC Such as BCC, SCC or Bowens Disease, and Melanoma) if They Occur Inside the Treatment Field | Actinic keratosis | 36 Number of lesions |
Primary
Changes in Blood Pressure (Systolic and Diastolic)
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.
Time frame: All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment
Population: One subject had elevated systolic and diastolic blood pressure at Visit 1 which was considered clinically significant and thus documented as relevant medical history. At Visit 2, blood pressure data was missing for one subject for the timepoint 'within 10 min prior to illumination', and for two subjects for the timepoint '60 min after illumination'. One subject missed Visit 3 and thus had no vital sign measurements at Visit 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Diastolic blood pressure - Visit 2 : Within 10 min after illumination | 7.1 mmHg | Standard Deviation 9.3 |
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Systolic blood pressure - Visit 2 : Within 10 min before illumination | 5.7 mmHg | Standard Deviation 12.8 |
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Systolic blood pressure - Visit 2 : Within 10 min after illumination | 17.3 mmHg | Standard Deviation 16.5 |
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Systolic blood pressure - Visit 2 : 60 min after illumination | 10.8 mmHg | Standard Deviation 15 |
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Systolic blood pressure - Visit 3 | 1.1 mmHg | Standard Deviation 12.5 |
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Systolic blood pressure - Visit 4 | -1.1 mmHg | Standard Deviation 13.4 |
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Systolic blood pressure - Visit 5 | -0.9 mmHg | Standard Deviation 14.5 |
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Diastolic blood pressure - Visit 2 : Within 10 min before illumination | 2.3 mmHg | Standard Deviation 6.6 |
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Diastolic blood pressure - Visit 2 : 60 min after illumination | 4.4 mmHg | Standard Deviation 7.9 |
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Diastolic blood pressure - Visit 3 | 1.0 mmHg | Standard Deviation 8.8 |
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Diastolic blood pressure - Visit 4 | -0.6 mmHg | Standard Deviation 8.3 |
| Total (BF-200 ALA) | Changes in Blood Pressure (Systolic and Diastolic) | Diastolic blood pressure - Visit 5 | 0.8 mmHg | Standard Deviation 8.5 |
Primary
Changes in Body Temperature
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.
Time frame: All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment
Population: At Visit 2, body temperature data was missing for one subject for the timepoint 'within 10 min prior to illumination', and for three subjects for the timepoint '60 min after illumination'. One subject missed Visit 3 and thus had no vital sign measurement at Visit 3. For one other subject, no temperature data was available at Visit 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total (BF-200 ALA) | Changes in Body Temperature | Visit 2 : Within 10 min prior to illumination | -0.11 °C | Standard Deviation 0.41 |
| Total (BF-200 ALA) | Changes in Body Temperature | Visit 2 : Within 10 min after illumination | -0.17 °C | Standard Deviation 0.6 |
| Total (BF-200 ALA) | Changes in Body Temperature | Visit 2 : 60 min after illumination | -0.08 °C | Standard Deviation 0.43 |
| Total (BF-200 ALA) | Changes in Body Temperature | Visit 3 | 0.04 °C | Standard Deviation 0.4 |
| Total (BF-200 ALA) | Changes in Body Temperature | Visit 4 | -0.05 °C | Standard Deviation 0.39 |
| Total (BF-200 ALA) | Changes in Body Temperature | Visit 5 | -0.03 °C | Standard Deviation 0.39 |
Primary
Changes in Pulse Rate
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.
Time frame: All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment
Population: At Visit 2, pulse rate data was missing for one subject for the timepoint 'within 10 min prior to illumination', and for two subjects for the timepoint '60 min after illumination'. One subject missed Visit 3 and thus had no vital sign measurements at Visit 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total (BF-200 ALA) | Changes in Pulse Rate | Visit 3 | 0.7 beats per min | Standard Deviation 9.8 |
| Total (BF-200 ALA) | Changes in Pulse Rate | Visit 4 | 0.7 beats per min | Standard Deviation 10 |
| Total (BF-200 ALA) | Changes in Pulse Rate | Visit 2 : Within 10 min prior to illumination | -2.1 beats per min | Standard Deviation 10 |
| Total (BF-200 ALA) | Changes in Pulse Rate | Visit 2 : Within 10 min after illumination | -1.2 beats per min | Standard Deviation 10.2 |
| Total (BF-200 ALA) | Changes in Pulse Rate | Visit 2 : 60 min after illumination | -2.8 beats per min | Standard Deviation 9.5 |
| Total (BF-200 ALA) | Changes in Pulse Rate | Visit 5 | 1.0 beats per min | Standard Deviation 9.2 |
Primary
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe).
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.
Time frame: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site exfoliation : moderate | 2.79 days | Standard Deviation 6.16 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site haemorrhage : all severities | 3.33 days | Standard Deviation 2.74 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site haemorrhage : moderate | 1.06 days | Standard Deviation 2.65 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site induration : all severities | 15.71 days | Standard Deviation 29.67 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site induration : mild | 12.41 days | Standard Deviation 30.72 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site pain : mild | 4.19 days | Standard Deviation 6.17 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site papules : all severities | 8.50 days | Standard Deviation 4.95 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site papules : mild | 8.50 days | Standard Deviation 4.95 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site paraesthesia : mild | 2.13 days | Standard Deviation 2.29 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site paraesthesia : moderate | 0.47 days | Standard Deviation 0.83 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site scab : mild | 7.53 days | Standard Deviation 8.52 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site swelling : mild | 5.83 days | Standard Deviation 4.22 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site vesicles : moderate | 0.39 days | Standard Deviation 1 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Blood pressure increased : all severities | 5.50 days | Standard Deviation 2.12 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Chills : moderate | 0.40 days | Standard Deviation 0.89 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Dry Eye : mild | 5.00 days | Standard Deviation 2.65 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Headache : mild | 2.15 days | Standard Deviation 2.12 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Nausea : mild | 0.50 days | Standard Deviation 0.71 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site paraesthesia : severe | 0.40 days | Standard Deviation 1.55 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site pruritus : all severities | 9.29 days | Standard Deviation 7.3 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site pruritus : mild | 8.06 days | Standard Deviation 7.42 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site pruritus : moderate | 1.13 days | Standard Deviation 3.64 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site pruritus : severe | 0.10 days | Standard Deviation 0.6 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site pustules : all severities | 5.67 days | Standard Deviation 1.53 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site pustules : mild | 3.83 days | Standard Deviation 2.84 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site pustules : moderate | 1.83 days | Standard Deviation 1.61 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site scab : all severities | 10.81 days | Standard Deviation 7.42 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site scab : moderate | 3.17 days | Standard Deviation 4.83 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site scab : severe | 0.11 days | Standard Deviation 0.79 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site swelling : all severities | 6.50 days | Standard Deviation 3.33 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site swelling : moderate | 0.67 days | Standard Deviation 1.63 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site vesicles : all severities | 5.07 days | Standard Deviation 4.08 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site vesicles : mild | 4.68 days | Standard Deviation 4 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site warmth : all severities | 2.13 days | Standard Deviation 1.75 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site warmth : mild | 0.72 days | Standard Deviation 0.97 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site warmth : moderate | 0.94 days | Standard Deviation 1.06 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site warmth : severe | 0.47 days | Standard Deviation 1.12 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Blood pressure increased : mild | 3.50 days | Standard Deviation 4.95 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Blood pressure increased : moderate | 2.00 days | Standard Deviation 2.83 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Chills : all severities | 1.60 days | Standard Deviation 0.89 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Chills : mild | 1.20 days | Standard Deviation 0.45 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Dry Eye : all severities | 5.00 days | Standard Deviation 2.65 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Fatigue : all severities | 4.50 days | Standard Deviation 1.29 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Fatigue : mild | 2.25 days | Standard Deviation 2.87 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Fatigue : moderate | 2.25 days | Standard Deviation 2.63 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Headache : all severities | 2.71 days | Standard Deviation 1.79 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Headache : moderate | 0.56 days | Standard Deviation 0.9 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Nausea : all severities | 1.00 days | Standard Deviation 0 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Nausea : moderate | 0.50 days | Standard Deviation 0.71 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Poor quality sleep : all severities | 7.50 days | Standard Deviation 0.71 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Poor quality sleep : mild | 4.00 days | Standard Deviation 5.66 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Poor quality sleep : moderate | 3.50 days | Standard Deviation 4.95 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site discharge : all severities | 5.50 days | Standard Deviation 3.32 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site discharge : mild | 5.50 days | Standard Deviation 3.32 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site discolouration : all severities | 11.17 days | Standard Deviation 5.6 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site discolouration : mild | 4.33 days | Standard Deviation 4.97 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site discolouration : moderate | 6.83 days | Standard Deviation 8.82 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site discomfort : all severities | 4.55 days | Standard Deviation 2.84 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site discomfort : mild | 4.55 days | Standard Deviation 2.84 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site dryness : all severities | 12.33 days | Standard Deviation 10.02 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site dryness : mild | 8.00 days | Standard Deviation 12.17 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site dryness : moderate | 4.33 days | Standard Deviation 7.51 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site erosion : all severities | 8.88 days | Standard Deviation 5.07 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site erosion : mild | 5.59 days | Standard Deviation 4.78 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site erosion : moderate | 2.81 days | Standard Deviation 5.37 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site erosion : severe | 0.47 days | Standard Deviation 1.88 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site erythema : all severities | 19.04 days | Standard Deviation 12.78 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site erythema : mild | 10.09 days | Standard Deviation 13.6 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site erythema : moderate | 7.95 days | Standard Deviation 10.11 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site erythema : severe | 1.00 days | Standard Deviation 4.8 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site exfoliation : all severities | 13.62 days | Standard Deviation 9.81 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site exfoliation : mild | 10.48 days | Standard Deviation 8.65 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site exfoliation : severe | 0.35 days | Standard Deviation 1.46 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site haemorrhage : mild | 2.28 days | Standard Deviation 2.31 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site hyperaesthesia : all severities | 6.22 days | Standard Deviation 3.27 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site hyperaesthesia : mild | 3.61 days | Standard Deviation 2.69 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site hyperaesthesia : moderate | 2.44 days | Standard Deviation 4.45 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site hyperaesthesia : severe | 0.17 days | Standard Deviation 0.5 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site induration : moderate | 3.29 days | Standard Deviation 4.86 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site oedema : all severities | 9.76 days | Standard Deviation 4.97 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site oedema : mild | 6.93 days | Standard Deviation 5.8 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site oedema : moderate | 2.69 days | Standard Deviation 3.78 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site oedema : severe | 0.15 days | Standard Deviation 0.86 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site pain : all severities | 8.91 days | Standard Deviation 7.11 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site pain : moderate | 2.84 days | Standard Deviation 4.99 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site pain : severe | 1.87 days | Standard Deviation 3.47 |
| Total (BF-200 ALA) | Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). | Application site paraesthesia : all severities | 3.00 days | Standard Deviation 2.39 |
Primary
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs).
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.
Time frame: Through study completion, on average 6 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any AEs | 888 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any AEs : mild | 563 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any AEs : moderate | 242 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any AEs : severe | 83 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any serious AEs | 0 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any TEAEs | 871 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any TEAEs : mild | 546 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any TEAEs : moderate | 242 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any TEAEs : severe | 83 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any serious TEAEs | 0 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any TEAEs leading to death | 0 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any TEAEs related to IMP | 809 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any TEAEs related to medical device | 782 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any TEAEs related to IMP or medical device | 811 Number of events |
| Total (BF-200 ALA) | Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). | Any TEAEs leading to study discontinuation | 0 Number of events |
Primary
Investigation of Clinical Chemistry Parameters
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.
Time frame: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)
Population: Visit 1: For one subject, clinical chemistry but no hematology parameters were analyzed, as the sample arrived at the analyzing laboratory too late. However, no clinical chemistry measurements were documented for this subject. One other subject had no blood sample collected at Visit 1. Visit 5: One subject had no hematology and clinical chemistry assessment at Visit 5, as the blood sample was inadvertently not collected.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total (BF-200 ALA) | Investigation of Clinical Chemistry Parameters | Visit 1 (Overall) | 1 participants with findings considered CS |
| Total (BF-200 ALA) | Investigation of Clinical Chemistry Parameters | Visit 1 - elevated blood glucose | 1 participants with findings considered CS |
| Total (BF-200 ALA) | Investigation of Clinical Chemistry Parameters | Visit 5 (Overall) | 2 participants with findings considered CS |
| Total (BF-200 ALA) | Investigation of Clinical Chemistry Parameters | Visit 5 - elevated alanine aminotransferase | 1 participants with findings considered CS |
| Total (BF-200 ALA) | Investigation of Clinical Chemistry Parameters | Visit 5 - elevated aspartate aminotransferase | 1 participants with findings considered CS |
| Total (BF-200 ALA) | Investigation of Clinical Chemistry Parameters | Visit 5 - elevated gamma glutamyl transferase | 2 participants with findings considered CS |
| Total (BF-200 ALA) | Investigation of Clinical Chemistry Parameters | Visit 5 - elevated blood glucose | 1 participants with findings considered CS |
Primary
Investigation of Hematology Parameters
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.
Time frame: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)
Population: Visit 1: For one subject, clinical chemistry but no hematology parameters were analyzed, as the sample arrived at the analyzing laboratory too late. However, no clinical chemistry measurements were documented for this subject. One other subject had no blood sample collected at Visit 1. Visit 5: One subject had no hematology and clinical chemistry assessment at Visit 5, as the blood sample was inadvertently not collected.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total (BF-200 ALA) | Investigation of Hematology Parameters | Visit 1 | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Investigation of Hematology Parameters | Visit 5 | 0 participants with findings considered CS |
Primary
Investigation of Urinalysis Parameters
Findings which differ from reference range and are considered to be clinically significant (CS) are to be reported
Time frame: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)
Population: Reasons for missing urinalysis data for 3 subjects at Visit 5 were study coordinator error (n=2) and urinalysis inadvertently not collected (n=1).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total (BF-200 ALA) | Investigation of Urinalysis Parameters | Visit 1 | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Investigation of Urinalysis Parameters | Visit 5 | 0 participants with findings considered CS |
Primary
Memory Tests
Including picture- and question-based memory tasks; abnormal findings that are considered clinically significant will be documented
Time frame: At screening (Visit 1, up to 14 days before treatment) and at Visit 2 (treatment day 1)
Population: Four subjects had missing data at Visit 1.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - All pictures memorized correctly | No answer | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - All pictures memorized correctly | Yes | 99 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - All pictures memorized correctly | No answer | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - All pictures memorized correctly | Yes | 96 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - All pictures memorized correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - Questions on personal identification answered correctly | No answer | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - Questions on personal identification answered correctly | Yes | 96 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - Questions on personal identification answered correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - Day of the week answered correctly | No answer | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - Day of the week answered correctly | Yes | 96 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - Day of the week answered correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - Arrival at site answered correctly | No answer | 2 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - Arrival at site answered correctly | Yes | 94 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - Arrival at site answered correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - 'Why here' answered correctly | No answer | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - 'Why here' answered correctly | Yes | 96 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 1 - 'Why here' answered correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - All pictures memorized correctly | No answer | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - All pictures memorized correctly | Yes | 100 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - All pictures memorized correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - Questions on personal identification answered correctly | No answer | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - Questions on personal identification answered correctly | Yes | 100 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - Questions on personal identification answered correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - Day of the week answered correctly | No answer | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - Day of the week answered correctly | Yes | 99 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - Day of the week answered correctly | No | 1 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - Arrival at site answered correctly | No answer | 1 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - Arrival at site answered correctly | Yes | 99 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - Arrival at site answered correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - 'Why here' answered correctly | No answer | 5 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - 'Why here' answered correctly | Yes | 95 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; prior PDT - 'Why here' answered correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - All pictures memorized correctly | No | 1 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Questions on personal identification answered correctly | No answer | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Questions on personal identification answered correctly | Yes | 100 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Questions on personal identification answered correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Day of the week answered correctly | No answer | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Day of the week answered correctly | Yes | 100 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Day of the week answered correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Arrival at site answered correctly | No answer | 1 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Arrival at site answered correctly | Yes | 99 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Arrival at site answered correctly | No | 0 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Remembered PDT | No answer | 14 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Remembered PDT | Yes | 85 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - Remembered PDT | No | 1 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - 'Why here' answered correctly | No answer | 4 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - 'Why here' answered correctly | Yes | 96 Participants |
| Total (BF-200 ALA) | Memory Tests | Visit 2; after end of illumination - 'Why here' answered correctly | No | 0 Participants |
Primary
Neurological Investigations
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
Time frame: At screening (Visit 1, up to 14 days before treatment) and at Visit 2 (treatment day 1)
Population: One subject had no sensitivity assessment at Visit 1, and one other subject had no sensitivity assessment at Visit 2 after end of illumination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total (BF-200 ALA) | Neurological Investigations | Visit 1 - Coordination | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Neurological Investigations | Visit 1 - Gait | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Neurological Investigations | Visit 1 - Sensitivity | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Neurological Investigations | Visit 2 prior PDT - Gait | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Neurological Investigations | Visit 1 - Pupils | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Neurological Investigations | Visit 2 prior PDT - Pupils | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Neurological Investigations | Visit 2 prior PDT - Coordination | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Neurological Investigations | Visit 2 prior PDT - Sensitivity | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Neurological Investigations | Visit 2 after end of illumination - Pupils | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Neurological Investigations | Visit 2 after end of illumination - Coordination | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Neurological Investigations | Visit 2 after end of illumination - Gait | 0 participants with findings considered CS |
| Total (BF-200 ALA) | Neurological Investigations | Visit 2 after end of illumination - Sensitivity | 0 participants with findings considered CS |
Primary
Physical Examination of Head, Neck, Skin, Lymph Nodes, Thorax Including Heart and Lungs, Abdomen, and Musculoskeletal, Peripheral Vascular and Nervous System Status
Abnormal findings, considered to be clinically significant (CS), are to be reported
Time frame: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)
Population: At Visit 1, one participant had findings considered clinically significant. Of this 1 participant, these findings concerned the nervous system.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total (BF-200 ALA) | Physical Examination of Head, Neck, Skin, Lymph Nodes, Thorax Including Heart and Lungs, Abdomen, and Musculoskeletal, Peripheral Vascular and Nervous System Status | Visit 1 | 1 participants with findings considered CS |
| Total (BF-200 ALA) | Physical Examination of Head, Neck, Skin, Lymph Nodes, Thorax Including Heart and Lungs, Abdomen, and Musculoskeletal, Peripheral Vascular and Nervous System Status | Of these: Findings concerning the nervous system | 1 participants with findings considered CS |
| Total (BF-200 ALA) | Physical Examination of Head, Neck, Skin, Lymph Nodes, Thorax Including Heart and Lungs, Abdomen, and Musculoskeletal, Peripheral Vascular and Nervous System Status | Visit 5 | 0 participants with findings considered CS |