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Safety and Efficacy Study for the Field-directed Treatment of Actinic Keratosis (AK) With Photodynamic Therapy (PDT)

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ClinicalTrials.gov Identifier: NCT01966120
Recruitment Status : Completed
First Posted : October 21, 2013
Results First Posted : December 19, 2016
Last Update Posted : December 19, 2016
Sponsor:
Information provided by (Responsible Party):
Biofrontera Bioscience GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Actinic Keratosis
Interventions Drug: BF-200 ALA gel
Drug: Placebo to BF-200 ALA gel
Procedure: Photodynamic therapy with BF-RhodoLED
Enrollment 87
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).
Arm/Group Title BF-200 ALA Placebo to BF-200 ALA
Hide Arm/Group Description

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.

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.

Period Title: Overall Study
Started 55 32
Completed 54 26
Not Completed 1 6
Reason Not Completed
Withdrawal by Subject             0             5
Lost to Follow-up             1             1
Arm/Group Title BF-200 ALA Placebo to BF-200 ALA Total
Hide Arm/Group Description

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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 55 32 87
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 32 participants 87 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
9
  16.4%
4
  12.5%
13
  14.9%
>=65 years
46
  83.6%
28
  87.5%
74
  85.1%
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 32 participants 87 participants
Female
5
   9.1%
3
   9.4%
8
   9.2%
Male
50
  90.9%
29
  90.6%
79
  90.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 32 participants 87 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
55
 100.0%
32
 100.0%
87
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 32 participants 87 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
55
 100.0%
32
 100.0%
87
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Germany Number Analyzed 55 participants 32 participants 87 participants
55 32 87
1.Primary Outcome
Title Overall Patient Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT)
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title BF-200 ALA Placebo to BF-200 ALA
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 55 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
90.9
(80 to 97)
21.9
(9.3 to 40)
2.Primary Outcome
Title Overall Patient Complete Response 12 Weeks After the Last PDT (PP)
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PP)
Arm/Group Title BF-200 ALA Placebo to BF-200 ALA
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 50 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
90.0
(78.2 to 96.7)
25.9
(11.1 to 46.3)
3.Secondary Outcome
Title Patient Histopathological Confirmed Response Rate
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title BF-200 ALA Placebo to BF-200 ALA
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 54 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
77.8
(64.4 to 88)
22.2
(8.6 to 42.3)
4.Secondary Outcome
Title Patient Complete Response 12 Weeks After PDT 1
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title BF-200 ALA Placebo to BF-200 ALA
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 55 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
61.8
(47.7 to 74.6)
9.4
(2 to 25)
5.Secondary Outcome
Title Lesion Complete Response 12 Weeks After Last PDT
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title BF-200 ALA Placebo to BF-200 ALA
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 55 32
Overall Number of Units Analyzed
Type of Units Analyzed: Number of Lesions Analyzed
298 173
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of lesions
94.3
(91 to 96.6)
32.9
(26 to 40.5)
6.Secondary Outcome
Title Patient Partial Response 12 Weeks After Last PDT
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title BF-200 ALA Placebo to BF-200 ALA
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 55 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
94.5
(84.9 to 98.9)
25
(11.5 to 43.4)
7.Secondary Outcome
Title Change of Total Lesion Area 12 Weeks After Last PDT
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title BF-200 ALA Placebo to BF-200 ALA
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 55 32
Mean (Standard Deviation)
Unit of Measure: percentage of lesion area change
-98.2  (9.65) -45.5  (42.96)
8.Secondary Outcome
Title Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title BF-200 ALA Placebo to BF-200 ALA
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 54 29
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Very good
35.2
(22.7 to 49.4)
17.2
(5.8 to 35.8)
Good
24.1
(13.5 to 37.6)
13.8
(3.9 to 31.7)
Satisfactory
24.1
(13.5 to 37.6)
20.7
(8 to 39.7)
Unsatisfactory
11.1
(4.2 to 22.6)
27.6
(12.7 to 47.2)
Impaired
5.6
(1.2 to 15.4)
20.7
(8 to 39.7)
9.Secondary Outcome
Title Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3
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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
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Full Analysis Set (FAS)
Arm/Group Title BF-200 ALA Placebo to BF-200 ALA
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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.

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.

Overall Number of Participants Analyzed 48 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Very good
39.6
(25.8 to 54.7)
19.2
(6.6 to 39.4)
Good
27.1
(15.3 to 41.8)
15.4
(4.4 to 34.9)
Satisfactory
22.9
(12 to 37.3)
23.1
(9 to 43.6)
Unsatisfactory
6.3
(1.3 to 17.2)
26.9
(11.6 to 47.8)
Impaired
4.2
(0.5 to 14.3)
15.4
(4.4 to 34.9)
Time Frame up to 11 months
Adverse Event Reporting Description 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.
 
Arm/Group Title BF-200 ALA Placebo to BF-200 ALA
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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.

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.

All-Cause Mortality
BF-200 ALA Placebo to BF-200 ALA
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
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BF-200 ALA Placebo to BF-200 ALA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/55 (3.64%)      0/32 (0.00%)    
Cardiac disorders     
Acute myocardial infarction  1  1/55 (1.82%)  1 0/32 (0.00%)  0
Injury, poisoning and procedural complications     
Femoral neck fracture  1  1/55 (1.82%)  1 0/32 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Bursitis  1  1/55 (1.82%)  1 0/32 (0.00%)  0
Nervous system disorders     
Cerebrovascular accident  1  1/55 (1.82%)  1 0/32 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BF-200 ALA Placebo to BF-200 ALA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   55/55 (100.00%)      22/32 (68.75%)    
General disorders     
Application site pain  1  53/55 (96.36%)  162 16/32 (50.00%)  30
Application site erythema  1  51/55 (92.73%)  76 11/32 (34.38%)  14
Application site pruritus  1  21/55 (38.18%)  25 9/32 (28.13%)  10
Application site scab  1  20/55 (36.36%)  26 1/32 (3.13%)  1
Application site exfoliation  1  17/55 (30.91%)  21 1/32 (3.13%)  1
Application site oedema  1  12/55 (21.82%)  14 1/32 (3.13%)  1
Application site vesicles  1  6/55 (10.91%)  6 0/32 (0.00%)  0
Application site discomfort  1  5/55 (9.09%)  7 0/32 (0.00%)  0
Application site discharge  1  3/55 (5.45%)  5 0/32 (0.00%)  0
Infections and infestations     
Nasopharyngitis  1  6/55 (10.91%)  7 0/32 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Clinical Trial Department,
Organization: Biofrontera Bioscience GmbH
Phone: +49 2148763226
Responsible Party: Biofrontera Bioscience GmbH
ClinicalTrials.gov Identifier: NCT01966120     History of Changes
Other Study ID Numbers: ALA-AK-CT007
2013-002510-12 ( EudraCT Number )
First Submitted: October 17, 2013
First Posted: October 21, 2013
Results First Submitted: June 10, 2016
Results First Posted: December 19, 2016
Last Update Posted: December 19, 2016