Trial Outcomes & Findings for Evaluation of Efficacy and Safety of BF-200 ALA Used With Photodynamic Therapy in Patients With Actinic Keratosis. (NCT NCT02799082)

NCT ID: NCT02799082

Last Updated: 2017-04-06

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 122 participants
• Primary outcome timeframe: 12 weeks after the last photodynamic therapy (PDT), up to 24 weeks
• Results posted on: 2017-04-06

Participant Flow

Study period: December 13, 2007 to October 01, 2008. Patients were recruited at 8 study centers in Germany (hospitals and private practices).

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).

Participant milestones

Measure	Vehicle Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin. Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).	BF-200 ALA Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).
Overall Study STARTED	41	81
Overall Study COMPLETED	37	77
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Measure	Vehicle Topical application of matched placebo gel (without containing active ingredient). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin. Vehicle: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).	BF-200 ALA Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1.0 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).
Overall Study Refused second PDT or withdraw consent	4	3
Overall Study Protocol Violation	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Vehicle n=40 Participants 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).	BF-200 ALA n=80 Participants 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 n=120 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Age, Categorical >=65 years	35 Participants n=5 Participants	70 Participants n=7 Participants	105 Participants n=5 Participants
Age, Continuous	70.8 years STANDARD_DEVIATION 6.7 • n=5 Participants	70.4 years STANDARD_DEVIATION 5.2 • n=7 Participants	70.5 years STANDARD_DEVIATION 5.7 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	72 Participants n=7 Participants	103 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	40 Participants n=5 Participants	80 Participants n=7 Participants	120 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Germany	40 participants n=5 Participants	80 participants n=7 Participants	120 participants n=5 Participants
Maximal severity of AK at baseline mild	11 participants n=5 Participants	19 participants n=7 Participants	30 participants n=5 Participants
Maximal severity of AK at baseline moderate	29 participants n=5 Participants	61 participants n=7 Participants	90 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks after the last photodynamic therapy (PDT), up to 24 weeks

Population: Full analysis set (FAS), Overall

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).

Outcome measures

Measure	Vehicle n=40 Participants 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).	BF-200 ALA n=80 Participants 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 Patient Clearance Rate 12 Weeks After the Last Photodynamic Therapy (PDT)	12.5 percentage of participants Interval 4.2 to 26.8	66.3 percentage of participants Interval 54.8 to 76.4

PRIMARY outcome

Timeframe: 12 weeks after the last PDT, up to 24 weeks

Population: per protocol population (PPP), (Overall)

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).

Outcome measures

Measure	Vehicle n=37 Participants 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).	BF-200 ALA n=77 Participants 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 Patient Clearance Rate 12 Weeks After the Last Photodynamic Therapy (PDT)	10.8 percentage of participants Interval 3.0 to 25.4	63.6 percentage of participants Interval 51.9 to 74.3

PRIMARY outcome

Timeframe: 12 weeks after the last PDT, up to 24 weeks

Population: FAS; subgroup analysis for patients only treated with narrow spectrum lamps

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)]

Outcome measures

Measure	Vehicle n=15 Participants 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).	BF-200 ALA n=31 Participants 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 Patient Clearance Rate Treated With Narrow Spectrum Lamp 12 Weeks After the Last Photodynamic Therapy (PDT)	13.3 percentage of participants Interval 1.7 to 40.5	87.1 percentage of participants Interval 70.2 to 96.4

PRIMARY outcome

Timeframe: 12 weeks after the last PDT, up to 24 weeks

Population: PPP; subgroup analysis for patients only treated with narrow spectrum lamps

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)]

Outcome measures

Measure	Vehicle n=13 Participants 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).	BF-200 ALA n=28 Participants 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 Patient Clearance Rate Treated With Narrow Spectrum Lamp 12 Weeks After the Last Photodynamic Therapy (PDT)	15.4 percentage of patients Interval 1.9 to 45.4	96.4 percentage of patients Interval 81.7 to 99.9

SECONDARY outcome

Timeframe: 12 weeks after the last PDT, up to 24 weeks

Population: FAS (Overall)

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

Outcome measures

Measure	Vehicle n=220 individual lesions 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).	BF-200 ALA n=455 individual lesions 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).
Percentage of AK Lesions Showing Complete Remission 12 Weeks After the Last PDT	20.9 percentage of lesions Interval 15.7 to 26.9	81.1 percentage of lesions Interval 77.2 to 84.6

SECONDARY outcome

Timeframe: 12 weeks after the last PDT, up to 24 weeks

Population: FAS, subgroup: lesions treated with narrow spectrum lamp only

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.

Outcome measures

Measure	Vehicle n=86 lesions -PDT with narrow spectrum lamp 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).	BF-200 ALA n=187 lesions -PDT with narrow spectrum lamp 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).
Percentage of AK Lesions Showing Complete Remission Treated With Narrow Spectrum Lamp 12 Weeks After the Last PDT	15.1 percentage of lesions Interval 8.3 to 24.5	96.3 percentage of lesions Interval 92.4 to 98.5

SECONDARY outcome

Timeframe: 12 weeks after the last PDT, up to 24 weeks

Population: FAS (Overall)

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.

Outcome measures

Measure	Vehicle n=40 Participants 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).	BF-200 ALA n=80 Participants 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).
Change in Total Lesion Size 12 Weeks After the Last PDT	-110.3 mm² Standard Deviation 207.9	-360.2 mm² Standard Deviation 194.5

SECONDARY outcome

Timeframe: 12 weeks after the last PDT, up to 24 weeks

Population: FAS

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.

Outcome measures

Measure	Vehicle n=29 Participants 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).	BF-200 ALA n=58 Participants 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).
Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Face)	-94.1 mm² Standard Deviation 213.0	-315.0 mm² Standard Deviation 198.9

SECONDARY outcome

Timeframe: 12 weeks after the last PDT, up to 24 weeks

Population: FAS

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.

Outcome measures

Measure	Vehicle n=15 Participants 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).	BF-200 ALA n=31 Participants 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).
Change in Total Lesion Area 12 Weeks After the Last PDT (Treated Area Scalp)	-112.3 mm² Standard Deviation 154.5	-340.2 mm² Standard Deviation 194.5

SECONDARY outcome

Timeframe: 12 weeks after the first PDT

Population: FAS

AK clearance rate, defined as the number of subjects with complete remission of all AK lesions assessed at 12 weeks after the first PDT

Outcome measures

Measure	Vehicle n=40 Participants 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).	BF-200 ALA n=80 Participants 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).
Subjects With Complete Clearance 12 Weeks After the First PDT	10.0 percentage of patients Interval 2.8 to 23.7	47.5 percentage of patients Interval 36.2 to 59.0

SECONDARY outcome

Timeframe: 12 weeks after the last PDT, up to 24 weeks

Population: FAS

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).

Outcome measures

Measure	Vehicle n=40 Participants 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).	BF-200 ALA n=80 Participants 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).
Subjects With Partial Clearance 12 Weeks After the Last PDT	17.5 percentage of patients Interval 7.3 to 32.8	78.8 percentage of patients Interval 68.2 to 87.1

SECONDARY outcome

Timeframe: 12 weeks after the last PDT, up to 24 weeks

Population: FAS

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.

Outcome measures

Measure	Vehicle n=40 Participants 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).	BF-200 ALA n=80 Participants 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 Cosmetic Outcome 12 Weeks After the Last PDT very good	4 Participants	19 Participants
Overall Cosmetic Outcome 12 Weeks After the Last PDT good	6 Participants	19 Participants
Overall Cosmetic Outcome 12 Weeks After the Last PDT satisfactory	21 Participants	39 Participants
Overall Cosmetic Outcome 12 Weeks After the Last PDT unsatisfactory	5 Participants	2 Participants
Overall Cosmetic Outcome 12 Weeks After the Last PDT impaired	4 Participants	1 Participants

SECONDARY outcome

Timeframe: during and after PDT [3h - 4 h]

Population: Safety Population, Overall reactions after first and/or second PDT

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).

Outcome measures

Measure	Vehicle n=41 Participants 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).	BF-200 ALA n=81 Participants 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).
Local Skin Reactions weeping/exudate	0 Participants	0 Participants
Local Skin Reactions erythema	15 Participants	72 Participants
Local Skin Reactions edema	1 Participants	32 Participants
Local Skin Reactions induration	0 Participants	12 Participants
Local Skin Reactions vesicles	0 Participants	0 Participants
Local Skin Reactions erosion	0 Participants	0 Participants
Local Skin Reactions ulceration	0 Participants	0 Participants
Local Skin Reactions scaling/flaking	0 Participants	3 Participants
Local Skin Reactions scabbing/crusting	0 Participants	2 Participants

SECONDARY outcome

Timeframe: during and after PDT [3h - 4 h]

Population: Safety Population (Overall reactions after first and/or second PDT)

Local discomfort experienced by the patient after illumination were documented in three categories: itching, burning, pain.

Outcome measures

Measure	Vehicle n=41 Participants 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).	BF-200 ALA n=81 Participants 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).
Discomfort During and After PDT pain	4 Participants	44 Participants
Discomfort During and After PDT itching	0 Participants	23 Participants
Discomfort During and After PDT burning	10 Participants	70 Participants

SECONDARY outcome

Timeframe: up to 24 weeks after the 1st PDT

Population: safety population

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).

Outcome measures

Measure	Vehicle n=41 Participants 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).	BF-200 ALA n=81 Participants 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).
Related Adverse Events /AEs) Application site erythema	15 Participants	72 Participants
Related Adverse Events /AEs) Application site irritation	10 Participants	70 Participants
Related Adverse Events /AEs) Application site pain	4 Participants	44 Participants
Related Adverse Events /AEs) Application site oedema	1 Participants	32 Participants
Related Adverse Events /AEs) Application site pruritus	0 Participants	27 Participants
Related Adverse Events /AEs) Application site induration	0 Participants	12 Participants
Related Adverse Events /AEs) Application site reaction	2 Participants	9 Participants

Adverse Events

Vehicle

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

BF-200 ALA

Serious events: 0 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vehicle n=41 participants at risk 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).	BF-200 ALA n=81 participants at risk 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).
Cardiac disorders Myocardial infarction	2.4% 1/41 • Number of events 1 • 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	0.00% 0/81 • 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
Musculoskeletal and connective tissue disorders Myositis	2.4% 1/41 • Number of events 1 • 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	0.00% 0/81 • 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

Other adverse events

Measure	Vehicle n=41 participants at risk 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).	BF-200 ALA n=81 participants at risk 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).
General disorders Application site erythema	36.6% 15/41 • Number of events 22 • 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	88.9% 72/81 • Number of events 116 • 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
General disorders Application site irritation	24.4% 10/41 • Number of events 11 • 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	86.4% 70/81 • Number of events 109 • 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
General disorders Application site pain	9.8% 4/41 • Number of events 4 • 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	54.3% 44/81 • Number of events 62 • 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
General disorders Application site oedema	2.4% 1/41 • Number of events 1 • 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	39.5% 32/81 • Number of events 39 • 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
General disorders Application site pruritus	0.00% 0/41 • 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	33.3% 27/81 • Number of events 32 • 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
General disorders Application site induration	0.00% 0/41 • 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	14.8% 12/81 • Number of events 14 • 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
General disorders Application site reaction	4.9% 2/41 • Number of events 2 • 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	11.1% 9/81 • Number of events 11 • 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

Additional Information

Dr. Beate Schmitz

Biofrontera Bioscience GmbH

Phone: +49 214 876 32

Email: b.schmitz@biofrontera.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER