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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-002510-12 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BF-200 ALA gel | Active Comparator | Photodynamic therapy with BF-RhodoLED in combination with BF-200 ALA. |
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| Placebo to BF-200 ALA gel | Placebo Comparator | Photodynamic therapy with BF-RhodoLED in combination with a nanoemulsion gel formulation similar to BF-200 ALA, but without the active ingredient 5-aminolevulinic acid. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BF-200 ALA gel | Drug | BF-200 ALA was applied over 1-2 fields of approximately 20 cm² in total, allowed to dry for approximately 10 minutes, and covered with occlusive tape material for 3 h. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
| 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Uwe Reinhold, Prof. Dr. | Dermatologisches Zentrum Bonn | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dermatologisches Zentrum Bonn Friedensplatz | Bonn | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39666443 | Derived | Reinhold U, Philipp-Dormston WG, Dirschka T, Ostendorf R, Aschoff R, Berking C, Jager A, Schmitz B, Foguet M, Szeimies RM. Long-term follow-up of a randomized, double-blind, phase III, multi-centre study to evaluate the safety and efficacy of field-directed photodynamic therapy (PDT) of mild to moderate actinic keratosis using BF-200 ALA versus placebo and the BF-RhodoLED(R) lamp. J Eur Acad Dermatol Venereol. 2025 Aug;39(8):1449-1459. doi: 10.1111/jdv.20452. Epub 2024 Dec 12. |
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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).
Trial was conducted in Germany with 7 study sites (Bonn, Dresden, Munich, Wuppertal, Mönchengladbach, Cologne, and Recklinghausen) who recruited patients.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 investigational medicinal product (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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo to BF-200 ALA gel | Drug | The reference product was a placebo (a nanoemulsion gel formulation similar to the Investigational Medicinal Product (IMP), but without the active ingredient). The placebo was packaged, assigned to each patient, and administered in the same way as the IMP. |
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| Photodynamic therapy with BF-RhodoLED | Procedure | After cleaning the lesions, the entire treatment field(s) were illuminated using the novel narrow spectrum BF-RhodoLED lamp, a red light illumination source (approximately 635 nm) developed by Biofrontera, until a total light dose of 37 J/cm² (per treated field) was achieved. |
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| 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 |
| 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. | 12 weeks after PDT 1 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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). | 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 |
| 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). | 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 |
| 12 months after last treatment (PDT-1 or PDT-2, if re-treated) |
| 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). | 12 months after last treatment (PDT-1 or PDT-2, if retreated) |
| 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. | 6 months after last treatment (PDT-1 or PDT-2, if re-treated) |
| 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. | 12 months after last treatment (PDT-1 or PDT-2, if re-treated) |
| 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. | 6 months after last treatment (PDT-1 or PDT-2, if re-treated) |
| 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. | 12 months after last treatment (PDT-1 or PDT-2, if re-treated) |
| FG001 | 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
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| 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. | Full Analysis Set (FAS) | Posted | Number | 95% Confidence Interval | percentage of participants | 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 |
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| 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. | Per Protocol Set (PP) | Posted | Number | 95% Confidence Interval | percentage of participants | 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 |
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| 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 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 |
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| 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. | Full Analysis Set (FAS) | Posted | Number | 95% Confidence Interval | percentage of participants | 12 weeks after PDT 1 |
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| 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. | Full Analysis Set (FAS) | Posted | Number | 95% Confidence Interval | percentage of lesions | 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 | Number of Lesions Analyzed | Number of Lesions Analyzed |
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| 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. | Full Analysis Set (FAS) | Posted | Number | 95% Confidence Interval | percentage of participants | 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 |
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| 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. | Full Analysis Set (FAS) | Posted | Mean | Standard Deviation | percentage of lesion area change | 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 |
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| 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). | Full Analysis Set (FAS) | Posted | Number | 95% Confidence Interval | percentage of participants | 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 |
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| 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). | Full Analysis Set (FAS) | Posted | Number | 95% Confidence Interval | percentage of participants | 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 |
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| 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). | 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). | Posted | Count of Participants | Participants | 12 months after last treatment (PDT-1 or PDT-2, if re-treated) |
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| 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). | 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). | Posted | Number | AK lesions | 12 months after last treatment (PDT-1 or PDT-2, if retreated) | AK Lesions | AK Lesions |
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| 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. | Full analysis set in follow-up (FAS-FUP), considering only patients with data at 6-months follow-up. | Posted | Count of Participants | Participants | 6 months after last treatment (PDT-1 or PDT-2, if re-treated) |
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| 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. | Full analysis set in follow-up (FAS-FUP), considering only patients with data at 12-months follow-up. | Posted | Count of Participants | Participants | 12 months after last treatment (PDT-1 or PDT-2, if re-treated) |
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| 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. | Full analysis set in follow-up (FAS-FUP), considering only patients with data at 6-months follow-up. | Posted | Number | 95% Confidence Interval | percentage of patients | 6 months after last treatment (PDT-1 or PDT-2, if re-treated) |
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| 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. | Full analysis set in follow-up (FAS-FUP), considering only patients with data at 12-months follow-up. | Posted | Number | 95% Confidence Interval | percentage of patients | 12 months after last treatment (PDT-1 or PDT-2, if re-treated) |
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up to 11 months
Adverse Events (AEs) expected to occur as local discomfort were reported via patient questionnaires, local skin reactions expected to occur were to be assessed by the assigned study team, any other AEs were to be reported by the patient or according to the assessment of the investigator.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 2 | 55 | 55 | 55 | ||
| EG001 | 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. | 0 | 32 | 22 | 32 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Application site pain | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Application site erythema | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Application site pruritus | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Application site scab | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Application site exfoliation | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Application site oedema | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Application site vesicles | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Application site discomfort | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Application site discharge | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
The only disclosure restriction on the PI is that the sponsor will review results communications prior to public release and has to approve in order to ensure the adequate reporting of study results. The sponsor can't refuse publication for unfair reasons.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Department, | Biofrontera Bioscience GmbH | +49 2148763226 | ameluz@biofrontera.com |
| ID | Term |
|---|---|
| D055623 | Keratosis, Actinic |
| ID | Term |
|---|---|
| D011230 | Precancerous Conditions |
| D009369 | Neoplasms |
| D007642 | Keratosis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000622 | Aminolevulinic Acid |
| D010778 | Photochemotherapy |
| C008848 | 1-phenyl-3,3-dimethyltriazene |
| ID | Term |
|---|---|
| D007982 | Levulinic Acids |
| D007651 | Keto Acids |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
| D004358 | Drug Therapy |
| D010789 | Phototherapy |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG001 | 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. |
|
|
| OG001 | 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. |
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|
|
|
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|
| OG001 | 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. |
|
|
| OG001 | 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. |
|
|
| OG001 | 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. |
|
|
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. |
|
|
| OG001 | 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. |
|
|
| OG001 | 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. |
|
|
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.
|
|
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.
|
|
| Moderate |
|
| Severe |
|
| Moderate |
|
| Severe |
|
| Moderate |
|
| Severe |
|
| Moderate |
|
| Severe |
|
| Moderate |
|
| Severe |
|
| Moderate |
|
| Severe |
|
| Moderate |
|
| Severe |
|
| Moderate |
|
| Severe |
|
| Moderate |
|
| Severe |
|
| Moderate |
|
| Severe |
|