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Evaluation of Efficacy and Safety of BF-200 ALA Used With Photodynamic Therapy in Patients With Actinic Keratosis.

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ClinicalTrials.gov Identifier: NCT02799082
Recruitment Status : Completed
First Posted : June 14, 2016
Results First Posted : April 6, 2017
Last Update Posted : April 6, 2017
Sponsor:
Information provided by (Responsible Party):
Biofrontera Bioscience GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Actinic Keratosis
Interventions Drug: Vehicle
Drug: BF-200 ALA
Enrollment 122
Recruitment Details Study period: December 13, 2007 to October 01, 2008. Patients were recruited at 8 study centers in Germany (hospitals and private practices).
Pre-assignment Details 128 patients were screened, of whom 122 patients were randomized (41 patients to the vehicle/placebo group, 81 patients to the BF-200 ALA group); 6 patients were screening failures (3 patients refused to participate, 3 patients meet exclusion criteria).
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Period Title: Overall Study
Started 41 81
Completed 37 77
Not Completed 4 4
Reason Not Completed
Refused second PDT or withdraw consent             4             3
Protocol Violation             0             1
Arm/Group Title Vehicle BF-200 ALA Total
Hide Arm/Group Description

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Total of all reporting groups
Overall Number of Baseline Participants 40 80 120
Hide Baseline Analysis Population Description
Baseline description is given for the FAS (Full Analysis Set). One patient each in the vehicle/placebo groupd and in the BF-200 ALA group dropped out without a post-treatment assessment of the target lesions and thus were not considered for the FAS.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 80 participants 120 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
5
  12.5%
10
  12.5%
15
  12.5%
>=65 years
35
  87.5%
70
  87.5%
105
  87.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants 80 participants 120 participants
70.8  (6.7) 70.4  (5.2) 70.5  (5.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 80 participants 120 participants
Female
9
  22.5%
8
  10.0%
17
  14.2%
Male
31
  77.5%
72
  90.0%
103
  85.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 80 participants 120 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
40
 100.0%
80
 100.0%
120
 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 40 participants 80 participants 120 participants
40 80 120
Maximal severity of AK at baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 40 participants 80 participants 120 participants
mild 11 19 30
moderate 29 61 90
1.Primary Outcome
Title Total Patient Clearance Rate 12 Weeks After the Last Photodynamic Therapy (PDT)
Hide Description AK clearance rate, defined as the percentage of subjects with complete remission of all AK lesions in the target area(s) assessed 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment).
Time Frame 12 weeks after the last photodynamic therapy (PDT), up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS), Overall
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 40 80
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12.5
(4.2 to 26.8)
66.3
(54.8 to 76.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vehicle, BF-200 ALA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments

The percentages stated relate to the total number of subjects for the respective week and treatment.

Cochran-Mantel-Haenszel Test stratified by center

Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Primary Outcome
Title Total Patient Clearance Rate 12 Weeks After the Last Photodynamic Therapy (PDT)
Hide Description AK clearance rate, defined as the percentage of subjects with complete remission of all AK lesions in the target area(s) assessed 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment).
Time Frame 12 weeks after the last PDT, up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
per protocol population (PPP), (Overall)
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 37 77
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
10.8
(3.0 to 25.4)
63.6
(51.9 to 74.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vehicle, BF-200 ALA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
3.Primary Outcome
Title Total Patient Clearance Rate Treated With Narrow Spectrum Lamp 12 Weeks After the Last Photodynamic Therapy (PDT)
Hide Description

AK clearance rate, defined as the percentage of subjects with complete remission of all AK lesions in the target area(s) assessed 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment).

Analysis was for the subgroup: treated by narrow spectrum lamps only [n=15 (vehicle), n= 31 (BF-200 ALA)]

Time Frame 12 weeks after the last PDT, up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS; subgroup analysis for patients only treated with narrow spectrum lamps
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 15 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13.3
(1.7 to 40.5)
87.1
(70.2 to 96.4)
4.Primary Outcome
Title Total Patient Clearance Rate Treated With Narrow Spectrum Lamp 12 Weeks After the Last Photodynamic Therapy (PDT)
Hide Description

AK clearance rate, defined as the percentage of subjects with complete remission of all AK lesions in the target area(s) assessed 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment).

Analysis was for the subgroup: treated by narrow spectrum lamps only [n=13 (vehicle), n= 28 (BF-200 ALA)]

Time Frame 12 weeks after the last PDT, up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PPP; subgroup analysis for patients only treated with narrow spectrum lamps
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 13 28
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
15.4
(1.9 to 45.4)
96.4
(81.7 to 99.9)
5.Secondary Outcome
Title Percentage of AK Lesions Showing Complete Remission 12 Weeks After the Last PDT
Hide Description Percentage of individual lesions completely cleared and with no adherent scaling plaques of AK that were visible any longer 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment); Overall population
Time Frame 12 weeks after the last PDT, up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS (Overall)
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 40 80
Overall Number of Units Analyzed
Type of Units Analyzed: Individual lesions
220 455
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of lesions
20.9
(15.7 to 26.9)
81.1
(77.2 to 84.6)
6.Secondary Outcome
Title Percentage of AK Lesions Showing Complete Remission Treated With Narrow Spectrum Lamp 12 Weeks After the Last PDT
Hide Description

Percentage of individual lesions completely cleared and with no adherent scaling plaques of AK that were visible any longer 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment).

for subgroup analysis: patients treated with narrow spectrum lamp only.

Time Frame 12 weeks after the last PDT, up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS, subgroup: lesions treated with narrow spectrum lamp only
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 15 31
Overall Number of Units Analyzed
Type of Units Analyzed: Lesions -PDT with narrow spectrum lamp
86 187
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of lesions
15.1
(8.3 to 24.5)
96.3
(92.4 to 98.5)
7.Secondary Outcome
Title Change in Total Lesion Size 12 Weeks After the Last PDT
Hide Description

Change in the mean total lesion area 12 weeks per subject after the last PDT compared to baseline (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment).

The outcome measure describes the mean difference between total lesion size at baseline and 12 weeks after the last PDT. Negative values indicate a reduction in the total lesion area size compared to baseline.

Time Frame 12 weeks after the last PDT, up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS (Overall)
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 40 80
Mean (Standard Deviation)
Unit of Measure: mm²
-110.3  (207.9) -360.2  (194.5)
8.Secondary Outcome
Title Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Face)
Hide Description

Change in mean total lesion area within the target treatment area per subject 12 weeks after the last PDT compared to baseline (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). The outcome measure describes the mean difference between total lesion size at baseline and 12 weeks after the last PDT. Negative values indicate a reduction in the total lesion area size compared to baseline.

Subgroup Analysis for patients with lesions located in the face only.

Time Frame 12 weeks after the last PDT, up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 29 58
Mean (Standard Deviation)
Unit of Measure: mm²
-94.1  (213.0) -315.0  (198.9)
9.Secondary Outcome
Title Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Scalp)
Hide Description

Change in mean total lesion area within the target treatment area per subject 12 weeks after the last PDT compared to baseline (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment). The outcome measure describes the mean difference between total lesion size at baseline and 12 weeks after the last PDT. Negative values indicate a reduction in the total lesion area size compared to baseline.

Subgroup Analysis for patients with lesions located in the scalp only.

Time Frame 12 weeks after the last PDT, up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 15 31
Mean (Standard Deviation)
Unit of Measure: mm²
-112.3  (154.5) -340.2  (194.5)
10.Secondary Outcome
Title Subjects With Complete Clearance 12 Weeks After the First PDT
Hide Description AK clearance rate, defined as the number of subjects with complete remission of all AK lesions assessed at 12 weeks after the first PDT
Time Frame 12 weeks after the first PDT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 40 80
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
10.0
(2.8 to 23.7)
47.5
(36.2 to 59.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vehicle, BF-200 ALA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
11.Secondary Outcome
Title Subjects With Partial Clearance 12 Weeks After the Last PDT
Hide Description Percentage of subjects with clearance of at least 75% of lesions 12 weeks after the last PDT (12 weeks after the 1st PDT or 12 weeks after the 2nd PDT in case of retreatment).
Time Frame 12 weeks after the last PDT, up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 40 80
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
17.5
(7.3 to 32.8)
78.8
(68.2 to 87.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vehicle
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
12.Secondary Outcome
Title Overall Cosmetic Outcome 12 Weeks After the Last PDT
Hide Description Overall Cosmetic Outcome (CO) 12 weeks after PDT (12 weeks after 1st PDT or 12 weeks after 2nd PDT). The cosmetic outcome at the end-of-study visit was calculated on the basis of skin quality assessment: skin surface, hyperpigmentation, hypopigmentation, mottled/irregular pigmentation, degree of scarring, and atrophy. The CO was rated as very good if the sum score of the previously mentioned ratings (all ratings for each sign added up) has improved by at least 2 points as compared to baseline; the CO was rated as good if the sum score at a given visit has improved by at least 1 point as compared to baseline; the cosmetic outcome is rated as satisfactory if the sum score at a given visit is identical to the one at baseline; the cosmetic outcome is rated as unsatisfactory if the sum score at a given visit has worsened by 1 point compared to baseline, the cosmetic outcome is rated as impaired if the sum score at a given visit has worsened by at least 2 points compared to baseline.
Time Frame 12 weeks after the last PDT, up to 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 40 80
Measure Type: Count of Participants
Unit of Measure: Participants
very good
4
  10.0%
19
  23.8%
good
6
  15.0%
19
  23.8%
satisfactory
21
  52.5%
39
  48.8%
unsatisfactory
5
  12.5%
2
   2.5%
impaired
4
  10.0%
1
   1.3%
13.Secondary Outcome
Title Local Skin Reactions
Hide Description Local skin reactions observed immediately after illumination by the investigator were documented using different categories (erythema, edema, induration, vesicles, erosion, ulceration, scaling/flanking, scabbing/crusting,weeping/exudates).
Time Frame during and after PDT [3h - 4 h]
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population, Overall reactions after first and/or second PDT
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 41 81
Measure Type: Count of Participants
Unit of Measure: Participants
erythema
15
  36.6%
72
  88.9%
edema
1
   2.4%
32
  39.5%
induration
0
   0.0%
12
  14.8%
vesicles
0
   0.0%
0
   0.0%
erosion
0
   0.0%
0
   0.0%
ulceration
0
   0.0%
0
   0.0%
scaling/flaking
0
   0.0%
3
   3.7%
scabbing/crusting
0
   0.0%
2
   2.5%
weeping/exudate
0
   0.0%
0
   0.0%
14.Secondary Outcome
Title Discomfort During and After PDT
Hide Description Local discomfort experienced by the patient after illumination were documented in three categories: itching, burning, pain.
Time Frame during and after PDT [3h - 4 h]
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population (Overall reactions after first and/or second PDT)
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 41 81
Measure Type: Count of Participants
Unit of Measure: Participants
pain
4
   9.8%
44
  54.3%
itching
0
   0.0%
23
  28.4%
burning
10
  24.4%
70
  86.4%
15.Secondary Outcome
Title Related Adverse Events /AEs)
Hide Description Related treatment-emerged-adverse events (TEAEs) until 12 weeks after the last PDT (>=5%) TEAEs were reported from the day of the 1st PDT until the end-of-study (clinical part), i.e. 12 weeks after the last PDT (until 12 weeks after the 1st PDT or up to 24 weeks in case a 2nd PDT was applied).
Time Frame up to 24 weeks after the 1st PDT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
safety population
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description:

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Overall Number of Participants Analyzed 41 81
Measure Type: Count of Participants
Unit of Measure: Participants
Application site erythema
15
  36.6%
72
  88.9%
Application site irritation
10
  24.4%
70
  86.4%
Application site pain
4
   9.8%
44
  54.3%
Application site oedema
1
   2.4%
32
  39.5%
Application site pruritus
0
   0.0%
27
  33.3%
Application site induration
0
   0.0%
12
  14.8%
Application site reaction
2
   4.9%
9
  11.1%
Time Frame up to 12 weeks after last treatment (PDT), i.e. 12 weeks after the first PDT or 12 weeks after the second PDT in case of retreatment
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vehicle BF-200 ALA
Hide Arm/Group Description

Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin.

BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).

All-Cause Mortality
Vehicle BF-200 ALA
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Vehicle BF-200 ALA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/41 (4.88%)      0/81 (0.00%)    
Cardiac disorders     
Myocardial infarction  1  1/41 (2.44%)  1 0/81 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Myositis  1  1/41 (2.44%)  1 0/81 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vehicle BF-200 ALA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/41 (48.78%)      78/81 (96.30%)    
General disorders     
Application site erythema  1  15/41 (36.59%)  22 72/81 (88.89%)  116
Application site irritation  1  10/41 (24.39%)  11 70/81 (86.42%)  109
Application site pain  1  4/41 (9.76%)  4 44/81 (54.32%)  62
Application site oedema  1  1/41 (2.44%)  1 32/81 (39.51%)  39
Application site pruritus  1  0/41 (0.00%)  0 27/81 (33.33%)  32
Application site induration  1  0/41 (0.00%)  0 12/81 (14.81%)  14
Application site reaction  1  2/41 (4.88%)  2 9/81 (11.11%)  11
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
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.
A publication or presentation of the study results may be planned and initiated by everybody of the scientific personnel involved in this clinical trial but not before the integrated report has been issued. Each party generating the manuscript for publication should allow the other parties a sufficient time in which to review and comment upon the prepublication manuscript.
Results Point of Contact
Name/Title: Dr. Beate Schmitz
Organization: Biofrontera Bioscience GmbH
Phone: +49 214 876 32 ext 41
Responsible Party: Biofrontera Bioscience GmbH
ClinicalTrials.gov Identifier: NCT02799082     History of Changes
Other Study ID Numbers: ALA-AK-CT003
First Submitted: May 27, 2016
First Posted: June 14, 2016
Results First Submitted: August 1, 2016
Results First Posted: April 6, 2017
Last Update Posted: April 6, 2017