Actinic Keratosis
Conditions
Keywords
Photodynamic Therapy, Field-directed Treatment
Brief summary
The purpose of this study is to evaluate the safety and efficacy of BF-200 ALA (Ameluz) versus placebo in the field-directed treatment of mild to moderate actinic keratosis with photodynamic therapy (PDT) when using the BF-RhodoLED lamp.
Detailed description
The study was performed as a randomized, multicentre, double-blind, placebo- controlled, parallel-group, phase III trial with BF-200 ALA and placebo in seven centres in Germany. A total of 94 patients were screened in this study; 87 were randomized (55 patients received BF-200 ALA, 32 received placebo). Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Illumination was performed with the PDT lamp BF-RhodoLED.
Interventions
DRUGBF-200 ALA gel
BF-200 ALA was applied over 1-2 fields of approximately 20 cm² in total, allowed to dry for approximately 10 minutes, and covered with occlusive tape material for 3 h.
DRUGPlacebo to BF-200 ALA gel
The reference product was a placebo (a nanoemulsion gel formulation similar to the Investigational Medicinal Product (IMP), but without the active ingredient). The placebo was packaged, assigned to each patient, and administered in the same way as the IMP.
PROCEDUREPhotodynamic therapy with BF-RhodoLED
After cleaning the lesions, the entire treatment field(s) were illuminated using the novel narrow spectrum BF-RhodoLED lamp, a red light illumination source (approximately 635 nm) developed by Biofrontera, until a total light dose of 37 J/cm² (per treated field) was achieved.
Sponsors
Biofrontera Bioscience GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Males or females between 18 and 85 years of age (inclusive) * Presence of 4 to 8 clinically confirmed actinic keratosis (AK) target lesions of mild to moderate intensity within 1-2 fields
Exclusion criteria
* History of hypersensitivity to 5-ALA or any ingredient of BF-200 ALA * Current treatment with immunosuppressive therapy * Presence of other malignant or benign tumors of the skin within the treatment area (eg malignant melanoma, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)) within the last 4 weeks * Confirmed diagnosis of SCC for the representative lesion by screening biopsy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Patient Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT) | 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT | All efficacy variables were evaluated for the FAS. The primary efficacy variable was also analyzed for the PP population. All subgroup analyses were carried out for the FAS. Data for size and grade of AK lesions were analyzed using the last observation carried forward (LOCF) approach, affecting the response rates evaluation. Due to the small amount of missing data in the study, which did not have any relevant impact on primary results, sensitivity analyses for missing data were not performed. The primary efficacy variable was the overall patient complete response 12 weeks after the last PDT. An overall complete responder was defined as a patient in whom all treated actinic keratosis (AK) lesions were cleared (Olsen score of 0) after the last PDT, i.e. after PDT 1 or after PDT 2 if re-treatment was performed. |
| Overall Patient Complete Response 12 Weeks After the Last PDT (PP) | 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT | All efficacy variables were evaluated for the FAS. The primary efficacy variable was also analyzed for the PP population. All subgroup analyses were carried out for the FAS. Data for size and grade of AK lesions were analyzed using the last observation carried forward (LOCF) approach, affecting the response rates evaluation. Due to the small amount of missing data in the study, which did not have any relevant impact on primary results, sensitivity analyses for missing data were not performed. The primary efficacy variable was the overall patient complete response 12 weeks after the last PDT. An overall complete responder was defined as a patient in whom all treated AK lesions were cleared (Olsen score of 0) after the last PDT, i.e. after PDT 1 or after PDT 2 if re-treatment was performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3 | 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT | Study personnel assessed and recorded the skin quality of the treated field(s) at baseline and at the end-of-study visit including skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring and atrophy. Upon visual examination of the treated field(s), the investigator coded the intensity of each skin parameter on a scale of 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. The cosmetic outcome evaluations were based on the sum score of the skin quality assessment (sum of all ratings for each skin parameter) at the end-of-study visit (Visit 4 or Visit 6, if retreated). The outcome was calculated using a 5-point scale ranging from very good (0) to impaired (4) based on the change of the skin quality assessments compared to baseline (0 = 2 points improvement; 1 = 1 point improvement; 2 = no change; 3 = 1 point worsened; 4 = at least 2 points worsened). |
| Patient Histopathological Confirmed Response Rate | 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT | For the secondary confirmatory analysis, several superiority hypotheses were tested within a pre-defined hierarchic multiple testing procedure as described in the Statistical Analysis Protocoll (SAP). The key secondary efficacy variables were tested strictly in a pre-defined order to ensure the family-wise error rate (FWER) and the testing procedure had to be stopped once the first non-significant test was obtained. The results of the confirmatory analysis are presented in the order pre-defined by the confirmatory testing procedure. Assessments of the patient histopathological confirmed response (HCR) rates were based on the results from the biopsy taken 12 weeks after the last PDT from a representative AK lesion selected at screening. If the biopsy result for a patient revealed a residual AK, the patient was considered not cleared for the analysis irrespectively of the investigator's clinical assessment. |
| Patient Complete Response 12 Weeks After PDT 1 | 12 weeks after PDT 1 | The second key secondary efficacy variable in the hierarchic test procedure was the patient complete response (complete clearance of all treated AK lesions) assessed at 12 weeks after PDT 1. |
| Lesion Complete Response 12 Weeks After Last PDT | 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT | The third key secondary efficacy variable in the hierarchic test procedure was the lesion complete response (completely cleared individual AK lesions) assessed at 12 weeks after last PDT. |
| Patient Partial Response 12 Weeks After Last PDT | 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT | The fourth key secondary efficacy variable in the hierarchic test procedure was the patient partial response (defined as complete clearance of at least 75% of treated AK lesions) assessed at 12 weeks after last PDT. |
| Change of Total Lesion Area 12 Weeks After Last PDT | 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT | The fifth key secondary efficacy variable in the hierarchic test procedure was the change from baseline in the total lesion area per patient assessed at 12 weeks after last PDT. |
| Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 | 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT | Study personnel assessed and recorded the skin quality of the treated field(s) at baseline and at the end-of-study visit including skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring and atrophy. Upon visual examination of the treated field(s), the investigator coded the intensity of each skin parameter on a scale of 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. The cosmetic outcome evaluations were based on the sum score of the skin quality assessment (sum of all ratings for each skin parameter) at the end-of-study visit (Visit 4 or Visit 6, if retreated). The outcome was calculated using a 5-point scale ranging from very good (0) to impaired (4) based on the change of the skin quality assessments compared to baseline (0 = 2 points improvement; 1 = 1 point improvement; 2 = no change; 3 = 1 point worsened; 4 = at least 2 points worsened). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Patient Recurrence Rate in Follow-up (Cumulative) | 12 months after last treatment (PDT-1 or PDT-2, if re-treated) | Cumulative numbers of patients with complete response who showed recurrences 12 months after last treatment (PDT-1 or PDT-2, if re-treated). A patient with complete response was regarded as recurrent if at least one baseline AK lesion recurred during the follow-up (FU). Complete response was achieved if all treated lesions of the patient were cleared 12 weeks after the last treatment (PDT-1 or PDT-2, if re-treated). Lesions that showed recurrence at 6-months (FU1) were also defined as recurrent at 12-months follow-up (FU2). |
| Skin Quality in Follow-up (6 Months) | 6 months after last treatment (PDT-1 or PDT-2, if re-treated) | Frequency of skin quality changes in follow-up compared to baseline. Study personnel assessed and recorded the skin quality of the treated field(s) at baseline and at the follow up visit (6 months) including skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring and atrophy. Upon visual examination of the treated field(s), the investigator coded the intensity of each skin parameter on a scale of 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. |
| Skin Quality in Follow-up (12 Months) | 12 months after last treatment (PDT-1 or PDT-2, if re-treated) | Frequency of skin quality changes in follow-up compared to baseline. Study personnel assessed and recorded the skin quality of the treated field(s) at baseline and at the follow up visit (12 months) including skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring and atrophy. Upon visual examination of the treated field(s), the investigator coded the intensity of each skin parameter on a scale of 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. |
| Patients' Satisfaction in Follow-up (6 Months) | 6 months after last treatment (PDT-1 or PDT-2, if re-treated) | Patients' satisfaction of the overall cosmetic outcome was assessed at 6-months follow-up visit using a 5-point scale, where 0=very good, 1=good, 2=satisfactory, 3=unsatisfactory, and 4=impaired. The lowest rating is the best outcome, the highest rating is the worst outcome. |
| Patients' Satisfaction in Follow-up (12 Months) | 12 months after last treatment (PDT-1 or PDT-2, if re-treated) | Patients' satisfaction of the overall cosmetic outcome was assessed at 12-months follow-up visit using a 5-point scale, where 0=very good, 1=good, 2=satisfactory, 3=unsatisfactory, and 4=impaired. The lowest rating is the best outcome, the highest rating is the worst outcome. |
| Lesion Recurrence Rate in Follow-up (Cumulative) | 12 months after last treatment (PDT-1 or PDT-2, if retreated) | Cumulative recurrence rate in follow-up of baseline AK lesions that were cleared 12 weeks after the last treatment (PDT-1 or PDT-2, if re-treated) and recurred during 12 months follow-up. Lesions that showed recurrence at 6-months (FU1) were also defined as recurrent at 12-months follow-up (FU2). |
Countries
Germany
Participant flow
Recruitment details
Trial was conducted in Germany with 7 study sites (Bonn, Dresden, Munich, Wuppertal, Mönchengladbach, Cologne, and Recklinghausen) who recruited patients.
Pre-assignment details
94 patients were screened, 87 patients were randomized (55 patients to BF-200 ALA and 32 patients to placebo) and treated. 7 patients were screening failures: 3 withdrew consent, 2 did not meet the in- /exclusion criteria, and 2 failed for other reasons (recruitment stop).
Participants by arm
| Arm | Count |
|---|---|
| BF-200 ALA Photodynamic therapy with BF-200 ALA
After lesion preparation, the entire content of 1 tube of verum was applied to the treatment fields identified for this study at screening. The verum was applied to the entire field(s) covering a size of approx. 20 cm² with a film of about 1 mm thickness. Application near the eyes, nostrils, mouth, ears, or mucosa was to be avoided (by a distance of 1 cm). After application, the IMP was allowed to dry for approx. 10 minutes before occlusion.
Following incubation of 3 hours (+/- 10 minutes) the dressing was removed and the remnant gel wiped off with a 0.9% saline solution. Thereafter illumination was performed using BF-RhodoLED lamp (635 nm) applying a total light dose of 37 J/cm² (per treated field). This treatment was performed once and repeated after 12 weeks if no complete response was observed. | 55 |
| Placebo to BF-200 ALA Photodynamic therapy with a nanoemulsion gel formulation similar to BF-200 ALA, but without the active ingredient 5-aminolevulinic acid.
After lesion preparation, the entire content of 1 tube of verum was applied to the treatment fields identified for this study at screening. The verum was applied to the entire field(s) covering a size of approx. 20 cm² with a film of about 1 mm thickness. Application near the eyes, nostrils, mouth, ears, or mucosa was to be avoided (by a distance of 1 cm). After application, the IMP was allowed to dry for approx. 10 minutes before occlusion.
Following incubation of 3 hours (+/- 10 minutes) the dressing was removed and the remnant gel wiped off with a 0.9% saline solution. Thereafter illumination was performed using BF-RhodoLED lamp (635 nm) applying a total light dose of 37 J/cm² (per treated field). This treatment was performed once and repeated after 12 weeks if no complete response was observed. | 32 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 5 |
Baseline characteristics
| Characteristic | BF-200 ALA | Placebo to BF-200 ALA | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 46 Participants | 28 Participants | 74 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 4 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 32 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 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 | 55 Participants | 32 Participants | 87 Participants |
| Region of Enrollment Germany | 55 participants | 32 participants | 87 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 50 Participants | 29 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 55 / 55 | 22 / 32 |
| serious Total, serious adverse events | 2 / 55 | 0 / 32 |
Outcome results
Primary
Overall Patient Complete Response 12 Weeks After the Last PDT (PP)
All efficacy variables were evaluated for the FAS. The primary efficacy variable was also analyzed for the PP population. All subgroup analyses were carried out for the FAS. Data for size and grade of AK lesions were analyzed using the last observation carried forward (LOCF) approach, affecting the response rates evaluation. Due to the small amount of missing data in the study, which did not have any relevant impact on primary results, sensitivity analyses for missing data were not performed. The primary efficacy variable was the overall patient complete response 12 weeks after the last PDT. An overall complete responder was defined as a patient in whom all treated AK lesions were cleared (Olsen score of 0) after the last PDT, i.e. after PDT 1 or after PDT 2 if re-treatment was performed.
Time frame: 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT
Population: Per Protocol Set (PP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BF-200 ALA | Overall Patient Complete Response 12 Weeks After the Last PDT (PP) | 90.0 percentage of participants |
| Placebo to BF-200 ALA | Overall Patient Complete Response 12 Weeks After the Last PDT (PP) | 25.9 percentage of participants |
Primary
Overall Patient Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT)
All efficacy variables were evaluated for the FAS. The primary efficacy variable was also analyzed for the PP population. All subgroup analyses were carried out for the FAS. Data for size and grade of AK lesions were analyzed using the last observation carried forward (LOCF) approach, affecting the response rates evaluation. Due to the small amount of missing data in the study, which did not have any relevant impact on primary results, sensitivity analyses for missing data were not performed. The primary efficacy variable was the overall patient complete response 12 weeks after the last PDT. An overall complete responder was defined as a patient in whom all treated actinic keratosis (AK) lesions were cleared (Olsen score of 0) after the last PDT, i.e. after PDT 1 or after PDT 2 if re-treatment was performed.
Time frame: 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BF-200 ALA | Overall Patient Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT) | 90.9 percentage of participants |
| Placebo to BF-200 ALA | Overall Patient Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT) | 21.9 percentage of participants |
Secondary
Change of Total Lesion Area 12 Weeks After Last PDT
The fifth key secondary efficacy variable in the hierarchic test procedure was the change from baseline in the total lesion area per patient assessed at 12 weeks after last PDT.
Time frame: 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BF-200 ALA | Change of Total Lesion Area 12 Weeks After Last PDT | -98.2 percentage of lesion area change | Standard Deviation 9.65 |
| Placebo to BF-200 ALA | Change of Total Lesion Area 12 Weeks After Last PDT | -45.5 percentage of lesion area change | Standard Deviation 42.96 |
Secondary
Lesion Complete Response 12 Weeks After Last PDT
The third key secondary efficacy variable in the hierarchic test procedure was the lesion complete response (completely cleared individual AK lesions) assessed at 12 weeks after last PDT.
Time frame: 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BF-200 ALA | Lesion Complete Response 12 Weeks After Last PDT | 94.3 percentage of lesions |
| Placebo to BF-200 ALA | Lesion Complete Response 12 Weeks After Last PDT | 32.9 percentage of lesions |
Secondary
Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3
Study personnel assessed and recorded the skin quality of the treated field(s) at baseline and at the end-of-study visit including skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring and atrophy. Upon visual examination of the treated field(s), the investigator coded the intensity of each skin parameter on a scale of 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. The cosmetic outcome evaluations were based on the sum score of the skin quality assessment (sum of all ratings for each skin parameter) at the end-of-study visit (Visit 4 or Visit 6, if retreated). The outcome was calculated using a 5-point scale ranging from very good (0) to impaired (4) based on the change of the skin quality assessments compared to baseline (0 = 2 points improvement; 1 = 1 point improvement; 2 = no change; 3 = 1 point worsened; 4 = at least 2 points worsened).
Time frame: 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 | Good | 24.1 percentage of participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 | Unsatisfactory | 11.1 percentage of participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 | Satisfactory | 24.1 percentage of participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 | Impaired | 5.6 percentage of participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 | Very good | 35.2 percentage of participants |
| Placebo to BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 | Impaired | 20.7 percentage of participants |
| Placebo to BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 | Very good | 17.2 percentage of participants |
| Placebo to BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 | Good | 13.8 percentage of participants |
| Placebo to BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 | Satisfactory | 20.7 percentage of participants |
| Placebo to BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 | Unsatisfactory | 27.6 percentage of participants |
Secondary
Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3
Study personnel assessed and recorded the skin quality of the treated field(s) at baseline and at the end-of-study visit including skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring and atrophy. Upon visual examination of the treated field(s), the investigator coded the intensity of each skin parameter on a scale of 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. The cosmetic outcome evaluations were based on the sum score of the skin quality assessment (sum of all ratings for each skin parameter) at the end-of-study visit (Visit 4 or Visit 6, if retreated). The outcome was calculated using a 5-point scale ranging from very good (0) to impaired (4) based on the change of the skin quality assessments compared to baseline (0 = 2 points improvement; 1 = 1 point improvement; 2 = no change; 3 = 1 point worsened; 4 = at least 2 points worsened).
Time frame: 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3 | Good | 27.1 percentage of participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3 | Unsatisfactory | 6.3 percentage of participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3 | Satisfactory | 22.9 percentage of participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3 | Impaired | 4.2 percentage of participants |
| BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3 | Very good | 39.6 percentage of participants |
| Placebo to BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3 | Impaired | 15.4 percentage of participants |
| Placebo to BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3 | Very good | 19.2 percentage of participants |
| Placebo to BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3 | Good | 15.4 percentage of participants |
| Placebo to BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3 | Satisfactory | 23.1 percentage of participants |
| Placebo to BF-200 ALA | Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3 | Unsatisfactory | 26.9 percentage of participants |
Secondary
Patient Complete Response 12 Weeks After PDT 1
The second key secondary efficacy variable in the hierarchic test procedure was the patient complete response (complete clearance of all treated AK lesions) assessed at 12 weeks after PDT 1.
Time frame: 12 weeks after PDT 1
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BF-200 ALA | Patient Complete Response 12 Weeks After PDT 1 | 61.8 percentage of participants |
| Placebo to BF-200 ALA | Patient Complete Response 12 Weeks After PDT 1 | 9.4 percentage of participants |
Secondary
Patient Histopathological Confirmed Response Rate
For the secondary confirmatory analysis, several superiority hypotheses were tested within a pre-defined hierarchic multiple testing procedure as described in the Statistical Analysis Protocoll (SAP). The key secondary efficacy variables were tested strictly in a pre-defined order to ensure the family-wise error rate (FWER) and the testing procedure had to be stopped once the first non-significant test was obtained. The results of the confirmatory analysis are presented in the order pre-defined by the confirmatory testing procedure. Assessments of the patient histopathological confirmed response (HCR) rates were based on the results from the biopsy taken 12 weeks after the last PDT from a representative AK lesion selected at screening. If the biopsy result for a patient revealed a residual AK, the patient was considered not cleared for the analysis irrespectively of the investigator's clinical assessment.
Time frame: 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT
Population: Full Analysis Set (FAS) 6 patients (1 BF-200 ALA and 5 Placebo patients) had a missing evaluation of the second biopsy 12 weeks after PDT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BF-200 ALA | Patient Histopathological Confirmed Response Rate | 77.8 percentage of participants |
| Placebo to BF-200 ALA | Patient Histopathological Confirmed Response Rate | 22.2 percentage of participants |
Secondary
Patient Partial Response 12 Weeks After Last PDT
The fourth key secondary efficacy variable in the hierarchic test procedure was the patient partial response (defined as complete clearance of at least 75% of treated AK lesions) assessed at 12 weeks after last PDT.
Time frame: 12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BF-200 ALA | Patient Partial Response 12 Weeks After Last PDT | 94.5 percentage of participants |
| Placebo to BF-200 ALA | Patient Partial Response 12 Weeks After Last PDT | 25 percentage of participants |
Other Pre-specified
Lesion Recurrence Rate in Follow-up (Cumulative)
Cumulative recurrence rate in follow-up of baseline AK lesions that were cleared 12 weeks after the last treatment (PDT-1 or PDT-2, if re-treated) and recurred during 12 months follow-up. Lesions that showed recurrence at 6-months (FU1) were also defined as recurrent at 12-months follow-up (FU2).
Time frame: 12 months after last treatment (PDT-1 or PDT-2, if retreated)
Population: Full analysis set in follow-up phase (FAS-FUP). Lesion recurrence rate was only analyzed in lesions which were cleared 12 weeks after the last treatment (PDT-1 or PDT-2, if re-treated).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BF-200 ALA | Lesion Recurrence Rate in Follow-up (Cumulative) | Baseline AK lesions cleared 12 weeks after last PDT with recurrence during 12 months FU | 25 AK lesions |
| BF-200 ALA | Lesion Recurrence Rate in Follow-up (Cumulative) | Baseline AK lesions cleared 12 weeks after last PDT and are still completely cleared at 12 months FU | 251 AK lesions |
| Placebo to BF-200 ALA | Lesion Recurrence Rate in Follow-up (Cumulative) | Baseline AK lesions cleared 12 weeks after last PDT with recurrence during 12 months FU | 1 AK lesions |
| Placebo to BF-200 ALA | Lesion Recurrence Rate in Follow-up (Cumulative) | Baseline AK lesions cleared 12 weeks after last PDT and are still completely cleared at 12 months FU | 51 AK lesions |
Other Pre-specified
Patient Recurrence Rate in Follow-up (Cumulative)
Cumulative numbers of patients with complete response who showed recurrences 12 months after last treatment (PDT-1 or PDT-2, if re-treated). A patient with complete response was regarded as recurrent if at least one baseline AK lesion recurred during the follow-up (FU). Complete response was achieved if all treated lesions of the patient were cleared 12 weeks after the last treatment (PDT-1 or PDT-2, if re-treated). Lesions that showed recurrence at 6-months (FU1) were also defined as recurrent at 12-months follow-up (FU2).
Time frame: 12 months after last treatment (PDT-1 or PDT-2, if re-treated)
Population: Full analysis set in follow-up phase (FAS-FUP). Recurrence rate was only analyzed in patients with complete clearance/response 12 weeks after the last treatment (PDT-1 or PDT-2, if re-treated). Complete response was achieved if all treated lesions of the patient were cleared 12 weeks after the last treatment (PDT-1 or PDT-2, if re-treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BF-200 ALA | Patient Recurrence Rate in Follow-up (Cumulative) | Patients cleared 12 weeks after last PDT with any recurrent baseline AK lesion at 12-months FU | 18 Participants |
| BF-200 ALA | Patient Recurrence Rate in Follow-up (Cumulative) | Patients cleared 12 weeks after last PDT still completely cleared at 12 months FU | 31 Participants |
| Placebo to BF-200 ALA | Patient Recurrence Rate in Follow-up (Cumulative) | Patients cleared 12 weeks after last PDT with any recurrent baseline AK lesion at 12-months FU | 1 Participants |
| Placebo to BF-200 ALA | Patient Recurrence Rate in Follow-up (Cumulative) | Patients cleared 12 weeks after last PDT still completely cleared at 12 months FU | 6 Participants |
Other Pre-specified
Patients' Satisfaction in Follow-up (12 Months)
Patients' satisfaction of the overall cosmetic outcome was assessed at 12-months follow-up visit using a 5-point scale, where 0=very good, 1=good, 2=satisfactory, 3=unsatisfactory, and 4=impaired. The lowest rating is the best outcome, the highest rating is the worst outcome.
Time frame: 12 months after last treatment (PDT-1 or PDT-2, if re-treated)
Population: Full analysis set in follow-up (FAS-FUP), considering only patients with data at 12-months follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Very good or good | 77.8 percentage of patients |
| BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Very good | 35.2 percentage of patients |
| BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Good | 42.6 percentage of patients |
| BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Satisfactory | 18.5 percentage of patients |
| BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Unsatisfactory | 3.7 percentage of patients |
| BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Impaired | 0.0 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Unsatisfactory | 3.8 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Very good or good | 69.2 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Satisfactory | 26.9 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Very good | 26.9 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Impaired | 0.0 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (12 Months) | Good | 42.3 percentage of patients |
Other Pre-specified
Patients' Satisfaction in Follow-up (6 Months)
Patients' satisfaction of the overall cosmetic outcome was assessed at 6-months follow-up visit using a 5-point scale, where 0=very good, 1=good, 2=satisfactory, 3=unsatisfactory, and 4=impaired. The lowest rating is the best outcome, the highest rating is the worst outcome.
Time frame: 6 months after last treatment (PDT-1 or PDT-2, if re-treated)
Population: Full analysis set in follow-up (FAS-FUP), considering only patients with data at 6-months follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Very good or good | 79.6 percentage of patients |
| BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Very good | 27.8 percentage of patients |
| BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Good | 51.9 percentage of patients |
| BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Satisfactory | 16.7 percentage of patients |
| BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Unsatisfactory | 3.7 percentage of patients |
| BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Impaired | 0.0 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Unsatisfactory | 11.1 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Very good or good | 59.3 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Satisfactory | 25.9 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Very good | 33.3 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Impaired | 3.7 percentage of patients |
| Placebo to BF-200 ALA | Patients' Satisfaction in Follow-up (6 Months) | Good | 25.9 percentage of patients |
Other Pre-specified
Skin Quality in Follow-up (12 Months)
Frequency of skin quality changes in follow-up compared to baseline. Study personnel assessed and recorded the skin quality of the treated field(s) at baseline and at the follow up visit (12 months) including skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring and atrophy. Upon visual examination of the treated field(s), the investigator coded the intensity of each skin parameter on a scale of 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
Time frame: 12 months after last treatment (PDT-1 or PDT-2, if re-treated)
Population: Full analysis set in follow-up (FAS-FUP), considering only patients with data at 12-months follow-up.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Moderate | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Skin surface (roughness/dryness/scaliness) | Mild | 14 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Skin surface (roughness/dryness/scaliness) | Moderate | 1 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Skin surface (roughness/dryness/scaliness) | Severe | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | None | 41 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Mild | 13 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Skin surface (roughness/dryness/scaliness) | None | 39 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Severe | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | None | 48 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Mild | 6 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Moderate | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Severe | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | None | 44 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Mild | 9 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Moderate | 1 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Severe | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Degree of scarring (independent of pigmentary changes) | None | 50 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Degree of scarring (independent of pigmentary changes) | Mild | 4 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Degree of scarring (independent of pigmentary changes) | Moderate | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Degree of scarring (independent of pigmentary changes) | Severe | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Atrophy | None | 52 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Atrophy | Mild | 2 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Atrophy | Moderate | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (12 Months) | Atrophy | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Atrophy | Moderate | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Skin surface (roughness/dryness/scaliness) | None | 15 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | None | 19 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Skin surface (roughness/dryness/scaliness) | Mild | 9 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Degree of scarring (independent of pigmentary changes) | Moderate | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Skin surface (roughness/dryness/scaliness) | Moderate | 2 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Mild | 4 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Skin surface (roughness/dryness/scaliness) | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Atrophy | Mild | 2 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | None | 16 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Moderate | 3 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Mild | 9 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Degree of scarring (independent of pigmentary changes) | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Moderate | 1 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Atrophy | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | None | 18 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Degree of scarring (independent of pigmentary changes) | None | 23 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Mild | 7 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Atrophy | None | 24 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Moderate | 1 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Degree of scarring (independent of pigmentary changes) | Mild | 3 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (12 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Severe | 0 Participants |
Other Pre-specified
Skin Quality in Follow-up (6 Months)
Frequency of skin quality changes in follow-up compared to baseline. Study personnel assessed and recorded the skin quality of the treated field(s) at baseline and at the follow up visit (6 months) including skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring and atrophy. Upon visual examination of the treated field(s), the investigator coded the intensity of each skin parameter on a scale of 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
Time frame: 6 months after last treatment (PDT-1 or PDT-2, if re-treated)
Population: Full analysis set in follow-up (FAS-FUP), considering only patients with data at 6-months follow-up.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Moderate | 3 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Skin surface (roughness/dryness/scaliness) | Mild | 15 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Skin surface (roughness/dryness/scaliness) | Moderate | 4 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Skin surface (roughness/dryness/scaliness) | Severe | 1 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | None | 35 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Mild | 16 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Skin surface (roughness/dryness/scaliness) | None | 34 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Severe | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | None | 42 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Mild | 10 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Moderate | 2 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Severe | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | None | 37 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Mild | 13 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Moderate | 4 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Severe | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Degree of scarring (independent of pigmentary changes) | None | 44 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Degree of scarring (independent of pigmentary changes) | Mild | 8 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Degree of scarring (independent of pigmentary changes) | Moderate | 2 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Degree of scarring (independent of pigmentary changes) | Severe | 0 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Atrophy | None | 48 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Atrophy | Mild | 4 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Atrophy | Moderate | 2 Participants |
| BF-200 ALA | Skin Quality in Follow-up (6 Months) | Atrophy | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Atrophy | Moderate | 2 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Skin surface (roughness/dryness/scaliness) | None | 15 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | None | 14 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Skin surface (roughness/dryness/scaliness) | Mild | 9 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Degree of scarring (independent of pigmentary changes) | Moderate | 2 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Skin surface (roughness/dryness/scaliness) | Moderate | 3 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Mild | 9 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Skin surface (roughness/dryness/scaliness) | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Atrophy | Mild | 4 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | None | 13 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Moderate | 4 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Mild | 10 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Degree of scarring (independent of pigmentary changes) | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Moderate | 4 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Mottled or irregular pigmentation (both hyper- and hypopigmentation | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hyperpigmentation (independent of texture change or hypopigmentation) | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Atrophy | Severe | 0 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | None | 15 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Degree of scarring (independent of pigmentary changes) | None | 20 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Mild | 9 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Atrophy | None | 21 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Moderate | 3 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Degree of scarring (independent of pigmentary changes) | Mild | 5 Participants |
| Placebo to BF-200 ALA | Skin Quality in Follow-up (6 Months) | Hypopigmentation (independent of texture change or hyperpigmentation) | Severe | 0 Participants |