Actinic Keratosis
Conditions
Brief summary
The aim of the study was to evaluate the efficacy and safety of BF-200 ALA (Ameluz) used with photodynamic therapy (PDT) in patients suffering from actinic keratosis.
Detailed description
The treatment comprised of one PDT session. If 12 weeks after PDT all lesions were cleared the patient entered the follow-up period. In case of remaining lesions or not completely cleared lesions the patient received a second PDT on the same day. The final assessment was performed 12 weeks after the last PDT and the patient moved to the follow-up phase.
Interventions
DRUGVehicle
topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).
DRUGBF-200 ALA
topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).
Sponsors
Biofrontera Bioscience GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subjects were willing and able to sign informed consent form. * Men and women aged between 18 and 85 years inclusive. * Subjects had a general good and stable health condition as confirmed by a physical examination and by medical history. * Subjects with clinically stable medical conditions including, but not limited to the following diseases were allowed to be included into the study, if the medication taken for the treatment of the disease did not match the criteria of the excluded or disallowed medications listed in points 7, 10, 11 and 12 of the
Exclusion criteria
* controlled hypertension * diabetes mellitus type II * hypercholesterolemia * osteoarthritis * Subjects accepted to abstain from sunbathing and the solarium during the study. * Subjects had at least 4 but not more than 8 clinically confirmed actinic keratosis (AK) target lesions of mild to moderate intensity within the face or bald scalp (excluding eyelids, lips and mucosa), i.e. AK grade I and II according to Olsen et. al. 1991. * To document and confirm the diagnosis of the investigators: * Photodocumentation of a representative lesion had to be evaluated and confirmed by an independent expert. * A pre-study biopsy had to be taken from a second representative AK lesion and was histopathologically evaluated by a dermato-pathological expert. * If the evaluation of the photo by the independent reviewer could not confirm the diagnosis of the investigator, then the biopsy result decided whether the subject was eligible for the study. * The AK lesions had to be discrete and quantifiable; the distance from one lesion to its neighbor lesion was greater than 1.0 cm * The diameter of each AK lesion was not less than 0.5 cm and not greater than 1.5 cm. The size of each baseline AK lesion was recorded by measuring the two largest perpendicular diameters. To describe irregular lesions (ellipsoidal) investigators measured the major and minor axis. Both axes had to be above the minimum of 0.5 cm and less than 1.5 cm. * The subjects were free of any significant physical abnormalities (e.g., tattoos, dermatoses) in the potential treatment area that might cause difficulty with examination or final evaluation. * The subjects were willing to stop using moisturizers and any other topical treatments with anti-aging products, vitamin A, vitamin C, and/or vitamin E containing ointments and creams, and green tea preparations during the study within the treatment area. Sunscreens were allowed, but were not to be applied in the treatment area within approximately 24 hours before a clinical visit with lesion count. * Women of childbearing potential were only allowed to participate in this study, if they used a highly effective method of contraception and had a negative serum pregnancy test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Patient Clearance Rate 12 Weeks After the Last Photodynamic Therapy (PDT) | 12 weeks after the last photodynamic therapy (PDT), up to 24 weeks | 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). |
| Total Patient Clearance Rate Treated With Narrow Spectrum Lamp 12 Weeks After the Last Photodynamic Therapy (PDT) | 12 weeks after the last PDT, up to 24 weeks | 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 \[n=15 (vehicle), n= 31 (BF-200 ALA)\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Lesion Size 12 Weeks After the Last PDT | 12 weeks after the last PDT, up to 24 weeks | Change in the mean total lesion area 12 weeks per subject after the last PDT compared to baseline (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). The outcome measure describes the mean difference between total lesion size at baseline and 12 weeks after the last PDT. Negative values indicate a reduction in the total lesion area size compared to baseline. |
| Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Face) | 12 weeks after the last PDT, up to 24 weeks | Change in mean total lesion area within the target treatment area per subject 12 weeks after the last PDT compared to baseline (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). The outcome measure describes the mean difference between total lesion size at baseline and 12 weeks after the last PDT. Negative values indicate a reduction in the total lesion area size compared to baseline. Subgroup Analysis for patients with lesions located in the face only. |
| Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Scalp) | 12 weeks after the last PDT, up to 24 weeks | Change in mean total lesion area within the target treatment area per subject 12 weeks after the last PDT compared to baseline (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). The outcome measure describes the mean difference between total lesion size at baseline and 12 weeks after the last PDT. Negative values indicate a reduction in the total lesion area size compared to baseline. Subgroup Analysis for patients with lesions located in the scalp only. |
| Subjects With Complete Clearance 12 Weeks After the First PDT | 12 weeks after the first PDT | AK clearance rate, defined as the number of subjects with complete remission of all AK lesions assessed at 12 weeks after the first PDT |
| Percentage of AK Lesions Showing Complete Remission 12 Weeks After the Last PDT | 12 weeks after the last PDT, up to 24 weeks | Percentage of individual lesions completely cleared and with no adherent scaling plaques of AK that were visible any longer 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment); Overall population |
| Overall Cosmetic Outcome 12 Weeks After the Last PDT | 12 weeks after the last PDT, up to 24 weeks | Overall Cosmetic Outcome (CO) 12 weeks after PDT (12 weeks after 1st PDT or 12 weeks after 2nd PDT). The cosmetic outcome at the end-of-study visit was calculated on the basis of skin quality assessment: skin surface, hyperpigmentation, hypopigmentation, mottled/irregular pigmentation, degree of scarring, and atrophy. The CO was rated as very good if the sum score of the previously mentioned ratings (all ratings for each sign added up) has improved by at least 2 points as compared to baseline; the CO was rated as good if the sum score at a given visit has improved by at least 1 point as compared to baseline; the cosmetic outcome is rated as satisfactory if the sum score at a given visit is identical to the one at baseline; the cosmetic outcome is rated as unsatisfactory if the sum score at a given visit has worsened by 1 point compared to baseline, the cosmetic outcome is rated as impaired if the sum score at a given visit has worsened by at least 2 points compared to baseline. |
| Local Skin Reactions | during and after PDT [3h - 4 h] | Local skin reactions observed immediately after illumination by the investigator were documented using different categories (erythema, edema, induration, vesicles, erosion, ulceration, scaling/flanking, scabbing/crusting,weeping/exudates). |
| Discomfort During and After PDT | during and after PDT [3h - 4 h] | Local discomfort experienced by the patient after illumination were documented in three categories: itching, burning, pain. |
| Related Adverse Events /AEs) | up to 24 weeks after the 1st PDT | Related treatment-emerged-adverse events (TEAEs) until 12 weeks after the last PDT (\>=5%) TEAEs were reported from the day of the 1st PDT until the end-of-study (clinical part), i.e. 12 weeks after the last PDT (until 12 weeks after the 1st PDT or up to 24 weeks in case a 2nd PDT was applied). |
| Subjects With Partial Clearance 12 Weeks After the Last PDT | 12 weeks after the last PDT, up to 24 weeks | Percentage of subjects with clearance of at least 75% of lesions 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). |
| Percentage of AK Lesions Showing Complete Remission Treated With Narrow Spectrum Lamp 12 Weeks After the Last PDT | 12 weeks after the last PDT, up to 24 weeks | Percentage of individual lesions completely cleared and with no adherent scaling plaques of AK that were visible any longer 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). for subgroup analysis: patients treated with narrow spectrum lamp only. |
Participant flow
Recruitment details
Study period: December 13, 2007 to October 01, 2008. Patients were recruited at 8 study centers in Germany (hospitals and private practices).
Pre-assignment details
128 patients were screened, of whom 122 patients were randomized (41 patients to the vehicle/placebo group, 81 patients to the BF-200 ALA group); 6 patients were screening failures (3 patients refused to participate, 3 patients meet exclusion criteria).
Participants by arm
| Arm | Count |
|---|---|
| Vehicle Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.
Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation). | 40 |
| BF-200 ALA Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.
BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation). | 80 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Refused second PDT or withdraw consent | 4 | 3 |
Baseline characteristics
| Characteristic | BF-200 ALA | Total | Vehicle |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 70 Participants | 105 Participants | 35 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 15 Participants | 5 Participants |
| Age, Continuous | 70.4 years STANDARD_DEVIATION 5.2 | 70.5 years STANDARD_DEVIATION 5.7 | 70.8 years STANDARD_DEVIATION 6.7 |
| Maximal severity of AK at baseline mild | 19 participants | 30 participants | 11 participants |
| Maximal severity of AK at baseline moderate | 61 participants | 90 participants | 29 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 80 Participants | 120 Participants | 40 Participants |
| Region of Enrollment Germany | 80 participants | 120 participants | 40 participants |
| Sex: Female, Male Female | 8 Participants | 17 Participants | 9 Participants |
| Sex: Female, Male Male | 72 Participants | 103 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 41 | 78 / 81 |
| serious Total, serious adverse events | 2 / 41 | 0 / 81 |
Outcome results
Primary
Total Patient Clearance Rate 12 Weeks After the Last Photodynamic Therapy (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).
Time frame: 12 weeks after the last photodynamic therapy (PDT), up to 24 weeks
Population: Full analysis set (FAS), Overall
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle | Total Patient Clearance Rate 12 Weeks After the Last Photodynamic Therapy (PDT) | 12.5 percentage of participants |
| BF-200 ALA | Total Patient Clearance Rate 12 Weeks After the Last Photodynamic Therapy (PDT) | 66.3 percentage of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Primary
Total Patient Clearance Rate 12 Weeks After the Last Photodynamic Therapy (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).
Time frame: 12 weeks after the last PDT, up to 24 weeks
Population: per protocol population (PPP), (Overall)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle | Total Patient Clearance Rate 12 Weeks After the Last Photodynamic Therapy (PDT) | 10.8 percentage of participants |
| BF-200 ALA | Total Patient Clearance Rate 12 Weeks After the Last Photodynamic Therapy (PDT) | 63.6 percentage of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Primary
Total Patient Clearance Rate Treated With Narrow Spectrum Lamp 12 Weeks After the Last Photodynamic Therapy (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). Analysis was for the subgroup: treated by narrow spectrum lamps only \[n=15 (vehicle), n= 31 (BF-200 ALA)\]
Time frame: 12 weeks after the last PDT, up to 24 weeks
Population: FAS; subgroup analysis for patients only treated with narrow spectrum lamps
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle | Total Patient Clearance Rate Treated With Narrow Spectrum Lamp 12 Weeks After the Last Photodynamic Therapy (PDT) | 13.3 percentage of participants |
| BF-200 ALA | Total Patient Clearance Rate Treated With Narrow Spectrum Lamp 12 Weeks After the Last Photodynamic Therapy (PDT) | 87.1 percentage of participants |
Primary
Total Patient Clearance Rate Treated With Narrow Spectrum Lamp 12 Weeks After the Last Photodynamic Therapy (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). Analysis was for the subgroup: treated by narrow spectrum lamps only \[n=13 (vehicle), n= 28 (BF-200 ALA)\]
Time frame: 12 weeks after the last PDT, up to 24 weeks
Population: PPP; subgroup analysis for patients only treated with narrow spectrum lamps
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle | Total Patient Clearance Rate Treated With Narrow Spectrum Lamp 12 Weeks After the Last Photodynamic Therapy (PDT) | 15.4 percentage of patients |
| BF-200 ALA | Total Patient Clearance Rate Treated With Narrow Spectrum Lamp 12 Weeks After the Last Photodynamic Therapy (PDT) | 96.4 percentage of patients |
Secondary
Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Face)
Change in mean total lesion area within the target treatment area per subject 12 weeks after the last PDT compared to baseline (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). The outcome measure describes the mean difference between total lesion size at baseline and 12 weeks after the last PDT. Negative values indicate a reduction in the total lesion area size compared to baseline. Subgroup Analysis for patients with lesions located in the face only.
Time frame: 12 weeks after the last PDT, up to 24 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Face) | -94.1 mm² | Standard Deviation 213 |
| BF-200 ALA | Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Face) | -315.0 mm² | Standard Deviation 198.9 |
Secondary
Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Scalp)
Change in mean total lesion area within the target treatment area per subject 12 weeks after the last PDT compared to baseline (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). The outcome measure describes the mean difference between total lesion size at baseline and 12 weeks after the last PDT. Negative values indicate a reduction in the total lesion area size compared to baseline. Subgroup Analysis for patients with lesions located in the scalp only.
Time frame: 12 weeks after the last PDT, up to 24 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Scalp) | -112.3 mm² | Standard Deviation 154.5 |
| BF-200 ALA | Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Scalp) | -340.2 mm² | Standard Deviation 194.5 |
Secondary
Change in Total Lesion Size 12 Weeks After the Last PDT
Change in the mean total lesion area 12 weeks per subject after the last PDT compared to baseline (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). The outcome measure describes the mean difference between total lesion size at baseline and 12 weeks after the last PDT. Negative values indicate a reduction in the total lesion area size compared to baseline.
Time frame: 12 weeks after the last PDT, up to 24 weeks
Population: FAS (Overall)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change in Total Lesion Size 12 Weeks After the Last PDT | -110.3 mm² | Standard Deviation 207.9 |
| BF-200 ALA | Change in Total Lesion Size 12 Weeks After the Last PDT | -360.2 mm² | Standard Deviation 194.5 |
Secondary
Discomfort During and After PDT
Local discomfort experienced by the patient after illumination were documented in three categories: itching, burning, pain.
Time frame: during and after PDT [3h - 4 h]
Population: Safety Population (Overall reactions after first and/or second PDT)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vehicle | Discomfort During and After PDT | burning | 10 Participants |
| Vehicle | Discomfort During and After PDT | pain | 4 Participants |
| Vehicle | Discomfort During and After PDT | itching | 0 Participants |
| BF-200 ALA | Discomfort During and After PDT | burning | 70 Participants |
| BF-200 ALA | Discomfort During and After PDT | pain | 44 Participants |
| BF-200 ALA | Discomfort During and After PDT | itching | 23 Participants |
Secondary
Local Skin Reactions
Local skin reactions observed immediately after illumination by the investigator were documented using different categories (erythema, edema, induration, vesicles, erosion, ulceration, scaling/flanking, scabbing/crusting,weeping/exudates).
Time frame: during and after PDT [3h - 4 h]
Population: Safety Population, Overall reactions after first and/or second PDT
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vehicle | Local Skin Reactions | edema | 1 Participants |
| Vehicle | Local Skin Reactions | ulceration | 0 Participants |
| Vehicle | Local Skin Reactions | vesicles | 0 Participants |
| Vehicle | Local Skin Reactions | scaling/flaking | 0 Participants |
| Vehicle | Local Skin Reactions | induration | 0 Participants |
| Vehicle | Local Skin Reactions | scabbing/crusting | 0 Participants |
| Vehicle | Local Skin Reactions | erosion | 0 Participants |
| Vehicle | Local Skin Reactions | weeping/exudate | 0 Participants |
| Vehicle | Local Skin Reactions | erythema | 15 Participants |
| BF-200 ALA | Local Skin Reactions | weeping/exudate | 0 Participants |
| BF-200 ALA | Local Skin Reactions | erythema | 72 Participants |
| BF-200 ALA | Local Skin Reactions | edema | 32 Participants |
| BF-200 ALA | Local Skin Reactions | induration | 12 Participants |
| BF-200 ALA | Local Skin Reactions | vesicles | 0 Participants |
| BF-200 ALA | Local Skin Reactions | erosion | 0 Participants |
| BF-200 ALA | Local Skin Reactions | ulceration | 0 Participants |
| BF-200 ALA | Local Skin Reactions | scaling/flaking | 3 Participants |
| BF-200 ALA | Local Skin Reactions | scabbing/crusting | 2 Participants |
Secondary
Overall Cosmetic Outcome 12 Weeks After the Last PDT
Overall Cosmetic Outcome (CO) 12 weeks after PDT (12 weeks after 1st PDT or 12 weeks after 2nd PDT). The cosmetic outcome at the end-of-study visit was calculated on the basis of skin quality assessment: skin surface, hyperpigmentation, hypopigmentation, mottled/irregular pigmentation, degree of scarring, and atrophy. The CO was rated as very good if the sum score of the previously mentioned ratings (all ratings for each sign added up) has improved by at least 2 points as compared to baseline; the CO was rated as good if the sum score at a given visit has improved by at least 1 point as compared to baseline; the cosmetic outcome is rated as satisfactory if the sum score at a given visit is identical to the one at baseline; the cosmetic outcome is rated as unsatisfactory if the sum score at a given visit has worsened by 1 point compared to baseline, the cosmetic outcome is rated as impaired if the sum score at a given visit has worsened by at least 2 points compared to baseline.
Time frame: 12 weeks after the last PDT, up to 24 weeks
Population: FAS
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vehicle | Overall Cosmetic Outcome 12 Weeks After the Last PDT | good | 6 Participants |
| Vehicle | Overall Cosmetic Outcome 12 Weeks After the Last PDT | unsatisfactory | 5 Participants |
| Vehicle | Overall Cosmetic Outcome 12 Weeks After the Last PDT | satisfactory | 21 Participants |
| Vehicle | Overall Cosmetic Outcome 12 Weeks After the Last PDT | impaired | 4 Participants |
| Vehicle | Overall Cosmetic Outcome 12 Weeks After the Last PDT | very good | 4 Participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After the Last PDT | impaired | 1 Participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After the Last PDT | very good | 19 Participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After the Last PDT | good | 19 Participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After the Last PDT | satisfactory | 39 Participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After the Last PDT | unsatisfactory | 2 Participants |
Secondary
Percentage of AK Lesions Showing Complete Remission 12 Weeks After the Last PDT
Percentage of individual lesions completely cleared and with no adherent scaling plaques of AK that were visible any longer 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment); Overall population
Time frame: 12 weeks after the last PDT, up to 24 weeks
Population: FAS (Overall)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle | Percentage of AK Lesions Showing Complete Remission 12 Weeks After the Last PDT | 20.9 percentage of lesions |
| BF-200 ALA | Percentage of AK Lesions Showing Complete Remission 12 Weeks After the Last PDT | 81.1 percentage of lesions |
Secondary
Percentage of AK Lesions Showing Complete Remission Treated With Narrow Spectrum Lamp 12 Weeks After the Last PDT
Percentage of individual lesions completely cleared and with no adherent scaling plaques of AK that were visible any longer 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). for subgroup analysis: patients treated with narrow spectrum lamp only.
Time frame: 12 weeks after the last PDT, up to 24 weeks
Population: FAS, subgroup: lesions treated with narrow spectrum lamp only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle | Percentage of AK Lesions Showing Complete Remission Treated With Narrow Spectrum Lamp 12 Weeks After the Last PDT | 15.1 percentage of lesions |
| BF-200 ALA | Percentage of AK Lesions Showing Complete Remission Treated With Narrow Spectrum Lamp 12 Weeks After the Last PDT | 96.3 percentage of lesions |
Secondary
Related Adverse Events /AEs)
Related treatment-emerged-adverse events (TEAEs) until 12 weeks after the last PDT (\>=5%) TEAEs were reported from the day of the 1st PDT until the end-of-study (clinical part), i.e. 12 weeks after the last PDT (until 12 weeks after the 1st PDT or up to 24 weeks in case a 2nd PDT was applied).
Time frame: up to 24 weeks after the 1st PDT
Population: safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vehicle | Related Adverse Events /AEs) | Application site pain | 4 Participants |
| Vehicle | Related Adverse Events /AEs) | Application site pruritus | 0 Participants |
| Vehicle | Related Adverse Events /AEs) | Application site irritation | 10 Participants |
| Vehicle | Related Adverse Events /AEs) | Application site induration | 0 Participants |
| Vehicle | Related Adverse Events /AEs) | Application site oedema | 1 Participants |
| Vehicle | Related Adverse Events /AEs) | Application site reaction | 2 Participants |
| Vehicle | Related Adverse Events /AEs) | Application site erythema | 15 Participants |
| BF-200 ALA | Related Adverse Events /AEs) | Application site reaction | 9 Participants |
| BF-200 ALA | Related Adverse Events /AEs) | Application site erythema | 72 Participants |
| BF-200 ALA | Related Adverse Events /AEs) | Application site irritation | 70 Participants |
| BF-200 ALA | Related Adverse Events /AEs) | Application site pain | 44 Participants |
| BF-200 ALA | Related Adverse Events /AEs) | Application site oedema | 32 Participants |
| BF-200 ALA | Related Adverse Events /AEs) | Application site pruritus | 27 Participants |
| BF-200 ALA | Related Adverse Events /AEs) | Application site induration | 12 Participants |
Secondary
Subjects With Complete Clearance 12 Weeks After the First PDT
AK clearance rate, defined as the number of subjects with complete remission of all AK lesions assessed at 12 weeks after the first PDT
Time frame: 12 weeks after the first PDT
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle | Subjects With Complete Clearance 12 Weeks After the First PDT | 10.0 percentage of patients |
| BF-200 ALA | Subjects With Complete Clearance 12 Weeks After the First PDT | 47.5 percentage of patients |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Subjects With Partial Clearance 12 Weeks After the Last PDT
Percentage of subjects with clearance of at least 75% of lesions 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment).
Time frame: 12 weeks after the last PDT, up to 24 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle | Subjects With Partial Clearance 12 Weeks After the Last PDT | 17.5 percentage of patients |
| BF-200 ALA | Subjects With Partial Clearance 12 Weeks After the Last PDT | 78.8 percentage of patients |
p-value: <0.0001Cochran-Mantel-Haenszel