Trial Outcomes & Findings for Evaluation of Safety and Efficacy of BF-200 ALA for the Treatment of Actinic Keratosis With Photodynamic Therapy (NCT NCT02799069)

Results Overview

An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT. The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

571 participants

Primary outcome timeframe

12 weeks after the last PDT, up to 24 weeks after the first treatment

Results posted on

2017-04-28

Participant Flow

Multinational / 26 centers sites: Germany (23), Austria (2) and Switzerland (1); 08 Apr 2008: First subject signed informed consent; 21 Aug 2009: Last subject completed clinical part of study

616 patients with actinic keratosis (AK) were planned to be randomized in a 3:3:1 ratio allowing for 20% of non-evaluable patients excluded from the per-protocol set. Due to the low drop out rates, recruiting was stopped after 600 patients were screened. Of those, 571 patients were randomized and 29 patients were screening failures.

Participant milestones

Participant milestones
Measure	Vehicle Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	MAL Cream Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Overall Study STARTED	76	248	247
Overall Study ITT/Safety	76	248	246
Overall Study COMPLETED	68	241	240
Overall Study NOT COMPLETED	8	7	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Vehicle Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	MAL Cream Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Overall Study Adverse Event	0	2	2
Overall Study Lack of Efficacy	2	0	0
Overall Study Lost to Follow-up	1	1	0
Overall Study Withdrawal by Subject	4	4	3
Overall Study Protocol Violation	1	0	2

Baseline Characteristics

Evaluation of Safety and Efficacy of BF-200 ALA for the Treatment of Actinic Keratosis With Photodynamic Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Total n=570 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=93 Participants	47 Participants n=4 Participants	38 Participants n=27 Participants	94 Participants n=483 Participants
Age, Categorical >=65 years	67 Participants n=93 Participants	201 Participants n=4 Participants	208 Participants n=27 Participants	476 Participants n=483 Participants
Age, Continuous	71.5 years STANDARD_DEVIATION 6.68 • n=93 Participants	70.2 years STANDARD_DEVIATION 7.18 • n=4 Participants	71.0 years STANDARD_DEVIATION 6.93 • n=27 Participants	70.7 years STANDARD_DEVIATION 7.01 • n=483 Participants
Sex: Female, Male Female	16 Participants n=93 Participants	34 Participants n=4 Participants	41 Participants n=27 Participants	91 Participants n=483 Participants
Sex: Female, Male Male	60 Participants n=93 Participants	214 Participants n=4 Participants	205 Participants n=27 Participants	479 Participants n=483 Participants
Region of Enrollment Europe	76 participants n=93 Participants	248 participants n=4 Participants	246 participants n=27 Participants	570 participants n=483 Participants
Number of individual lesions	490 individual lesions n=93 Participants	1504 individual lesions n=4 Participants	1557 individual lesions n=27 Participants	3551 individual lesions n=483 Participants

PRIMARY outcome

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

Population: Intent-to-treat (ITT)

An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT. The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), ITT	64.2 percentage of patients Interval 57.9 to 70.2	17.1 percentage of patients Interval 9.4 to 27.5	78.2 percentage of patients Interval 72.6 to 83.2

PRIMARY outcome

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

Population: per protocol set (PP)

An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT. The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)

Outcome measures

Outcome measures
Measure	MAL Cream n=236 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=65 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=238 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), PP	65.3 percentage of patients Interval 58.8 to 71.3	20.0 percentage of patients Interval 11.1 to 31.8	79.4 percentage of patients Interval 73.7 to 84.4

PRIMARY outcome

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

Population: ITT

Subgroup analysis of patients treated with a narrow spectrum device for PDT Illumination (\~630 nm). An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT. The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)

Outcome measures

Outcome measures
Measure	MAL Cream n=126 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=39 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=125 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only	67.5 percentage of patients Interval 58.5 to 75.5	12.8 percentage of patients Interval 4.3 to 27.4	84.8 percentage of patients Interval 77.3 to 90.6

SECONDARY outcome

Timeframe: 3-4 weeks after the first PDT

Population: ITT

A complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) at 3-4 weeks after the first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Complete Response 3-4 Weeks After First Photodynamic Therapy (PDT)	24.8 percentage of patients Interval 19.5 to 30.7	2.6 percentage of patients Interval 0.3 to 9.2	34.7 percentage of patients Interval 28.8 to 41.0

SECONDARY outcome

Timeframe: 12 weeks after the first PDT

Population: ITT

A complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) at 12 weeks after the first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Complete Response 12 Weeks After First Photodynamic Therapy (PDT)	37.0 percentage of patients Interval 30.9 to 43.4	3.9 percentage of patients Interval 0.8 to 11.1	48.4 percentage of patients Interval 42.0 to 54.8

SECONDARY outcome

Timeframe: 3-4 weeks after the second PDT, 15-16 weeks after first treatment

Population: ITT

A complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) at 3-4 weeks after the second PDT. A second PDT was applied in case partial- or non-responding lesions remained 12 weeks after the first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=155 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=73 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=128 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Complete Response 3-4 Weeks After the Second Photodynamic Therapy (PDT)	43.9 percentage of patients Interval 35.9 to 52.1	13.7 percentage of patients Interval 6.8 to 23.8	48.4 percentage of patients Interval 39.5 to 57.4

SECONDARY outcome

Timeframe: 12 weeks after the second PDT, 24 weeks after first treatment

Population: ITT

A complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) at 12 weeks after the second PDT. A second PDT was applied in case partial- or non-responding lesions remained 12 weeks after the first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=155 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=73 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=128 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Complete Response 12 Weeks After Second Photodynamic Therapy (PDT)	43.2 percentage of patients Interval 35.3 to 51.4	13.7 percentage of patients Interval 6.8 to 23.8	57.8 percentage of patients Interval 48.8 to 66.5

SECONDARY outcome

Timeframe: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment

Population: ITT

A complete responder at week 3-4 after treatment was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission). This outcome measure considered patients who were completely cleared at 3-4 weeks after the last PDT which included complete responders 3-4 weeks after the first and complete responders 3-4 weeks after the second PDT ( a second PDT was applied in case of remaining lesions 12 weeks after the first PDT).

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Complete Response 3-4 Weeks After Last Photodynamic Therapy (PDT)	43.9 percentage of patients Interval 37.6 to 50.3	14.5 percentage of patients Interval 7.5 to 24.4	54.0 percentage of patients Interval 47.6 to 60.4

SECONDARY outcome

Timeframe: 3-4 weeks after the first PDT

Population: ITT

A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 3-4 weeks after the first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Partial Response at 3-4 Weeks After First Photodynamic Therapy (PDT)	45.9 percentage of patients Interval 39.6 to 52.4	2.6 percentage of patients Interval 0.3 to 9.2	50.0 percentage of patients Interval 43.6 to 56.4

SECONDARY outcome

Timeframe: 12 weeks after the first PDT

Population: ITT

A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 12 weeks after the first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Partial Response at 12 Weeks After the First Photodynamic Therapy (PDT)	53.3 percentage of patients Interval 46.8 to 59.6	13.2 percentage of patients Interval 6.5 to 22.9	58.9 percentage of patients Interval 52.5 to 65.1

SECONDARY outcome

Timeframe: 3-4 weeks after the second PDT, 15-16 weeks after first treatment

Population: ITT

A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 3-4 weeks after the second PDT. A second PDT was applied in case of partial- or non-responding lesions 12 weeks after the first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=155 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=73 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=128 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Partial Response at 3-4 Weeks After the Second Photodynamic Therapy (PDT)	62.6 percentage of patients Interval 54.5 to 70.2	20.5 percentage of patients Interval 12.0 to 31.6	68.0 percentage of patients Interval 59.1 to 75.9

SECONDARY outcome

Timeframe: 12 weeks after the second PDT, 24 weeks after first treatment

Population: ITT

A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 12 weeks after the second PDT. A second PDT was applied in case of partial- or non-responding lesions 12 weeks after the first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=155 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=73 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=128 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Partial Response at 12 Weeks After the Second Photodynamic Therapy (PDT)	65.2 percentage of patients Interval 57.1 to 72.6	23.3 percentage of patients Interval 14.2 to 34.6	73.4 percentage of patients Interval 64.9 to 80.9

SECONDARY outcome

Timeframe: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment

Population: ITT

A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 3-4 weeks after last PDT. The outcome measure combined partial responders with at least 75% of lesions cleared at 3-4 weeks after the first PDT or after the second PDT (a second PDT was applied in case of partial- or non-responding lesions 12 weeks after the first PDT).

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Partial Response at 3-4 Weeks After Last Photodynamic Therapy (PDT)	64.6 percentage of patients Interval 58.3 to 70.6	21.1 percentage of patients Interval 12.5 to 31.9	70.6 percentage of patients Interval 64.5 to 76.2

SECONDARY outcome

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

Population: ITT

A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 12 weeks after last PDT. The outcome measure combined partial responders with at least 75% of lesions cleared at 12 weeks after the first PDT and after the second PDT (a second PDT was applied in case of partial- or non-responding lesions 12 weeks after the first PDT) .

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Percentage of Participants With Partial Response at 12 Weeks After Last Photodynamic Therapy (PDT)	78.0 percentage of patients Interval 72.3 to 83.1	26.3 percentage of patients Interval 16.9 to 37.7	87.1 percentage of patients Interval 82.3 to 91.0

SECONDARY outcome

Timeframe: 3-4 weeks after the first PDT

Population: ITT

Completely cleared individual lesions as defined at 3-4 weeks after first photodynamic therapy (PDT)

Outcome measures

Outcome measures
Measure	MAL Cream n=1557 number of individual lesions Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=490 number of individual lesions Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=1504 number of individual lesions Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Complete Lesion Response Rate 3-4 Weeks After First Photodynamic Therapy (PDT)	58.8 percentage of lesions Interval 56.3 to 61.3	12.7 percentage of lesions Interval 9.8 to 15.9	63.9 percentage of lesions Interval 61.4 to 66.3

SECONDARY outcome

Timeframe: 12 weeks after the first PDT

Population: ITT

Completely cleared individual lesions as defined at 12 weeks after the first photodynamic therapy (PDT).

Outcome measures

Outcome measures
Measure	MAL Cream n=1557 number of individual lesions Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=490 number of individual lesions Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=1504 number of individual lesions Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Complete Lesion Response Rate 12 Weeks After First Photodynamic Therapy (PDT)	66.5 percentage of lesions Interval 64.1 to 68.8	24.7 percentage of lesions Interval 20.9 to 28.8	73.8 percentage of lesions Interval 71.5 to 76.0

SECONDARY outcome

Timeframe: 3-4 weeks after the second PDT, 15-16 weeks after first treatment

Population: ITT

Completely cleared individual lesions as defined at 3-4 weeks after the second PDT. A second PDT was applied in case the individual lesion showed no or partial response12 weeks after first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=522 number of individiual lesions Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=369 number of individiual lesions Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=394 number of individiual lesions Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Complete Lesion Response Rate 3-4 Weeks After the Second Photodynamic Therapy (PDT)	54.8 percentage of lesions Interval 50.4 to 59.1	16.3 percentage of lesions Interval 12.6 to 20.4	60.4 percentage of lesions Interval 55.4 to 65.3

SECONDARY outcome

Timeframe: 12 weeks after the second PDT, 24 weeks after first treatment

Population: ITT

Completely cleared individual lesions as defined at 12 weeks after second PDT. A second PDT was applied in case the individual lesion showed no or partial response 12 weeks after first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=522 number of individual lesions Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=369 number of individual lesions Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=394 number of individual lesions Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Complete Lesion Response Rate 12 Weeks After Second PDT	58.0 percentage of lesions Interval 53.7 to 62.3	22.0 percentage of lesions Interval 17.8 to 26.5	69.3 percentage of lesions Interval 64.5 to 73.8

SECONDARY outcome

Timeframe: 3-4 weeks after the last PDT, up to 16 weeks after first treatment

Population: ITT

Completely cleared individual lesions defined at 3-4 weeks after the last PDT comprising of completely cleared individual lesions 3-4 weeks after the first and after the second PDT (a second PDT was applied in case lesions show no or partial response 12 weeks after the first PDT).

Outcome measures

Outcome measures
Measure	MAL Cream n=1557 number of individual lesions Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=490 number of individual lesions Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=1504 number of individual lesions Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Complete Lesion Response Rate 3-4 Weeks After Last Photodynamic Therapy (PDT)	73.5 percentage of lesions Interval 71.2 to 75.7	31.4 percentage of lesions Interval 27.3 to 35.7	79.0 percentage of lesions Interval 76.8 to 81.0

SECONDARY outcome

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

Population: ITT

Completely cleared individual lesions 12 weeks after last PDT comprising of completely cleared individual lesions 12 weeks after the first or second PDT (a second PDT was applied in case individual lesions show no or partial response 12 weeks after first PDT).

Outcome measures

Outcome measures
Measure	MAL Cream n=1557 num,ber of individual lesions Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=490 num,ber of individual lesions Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=1504 num,ber of individual lesions Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Complete Lesion Response Rate 12 Weeks After Last Photodynamic Therapy (PDT)	83.2 percentage of lesions Interval 81.2 to 85.0	37.1 percentage of lesions Interval 32.9 to 41.6	90.4 percentage of lesions Interval 88.8 to 91.8

SECONDARY outcome

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

Population: ITT

Completely cleared individual lesions 12 weeks after last PDT comprising of individual cleared lesions 12 weeks after the first or second PDT. A second PDT was applied in case individual lesion showed no or partial response 12 weeks after the first PDT. Lesions were illuminated during photodynamic therapy with narrow spectrum devices only (\~630 nm).

Outcome measures

Outcome measures
Measure	MAL Cream n=847 lesions treated with narrow spectrum Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=268 lesions treated with narrow spectrum Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=831 lesions treated with narrow spectrum Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Complete Lesion Response Rates 12 Weeks After Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only	89.3 percentage of lesions Interval 87.0 to 91.3	32.5 percentage of lesions Interval 26.9 to 38.4	93.6 percentage of lesions Interval 91.7 to 95.2

SECONDARY outcome

Timeframe: 3-4 weeks after the first PDT

Population: ITT

Percentage of change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed at 3-4 weeks after the first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Change From Baseline in Total Lesion Area 3-4 Weeks After the First Photodynamic Therapy (PDT)	-75.7 percentage of change from baseline Standard Deviation 27.76	-26.9 percentage of change from baseline Standard Deviation 32.74	-78.9 percentage of change from baseline Standard Deviation 27.71

SECONDARY outcome

Timeframe: 12 weeks after the first PDT

Population: ITT

the change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed 12 weeks after the first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Change From Baseline in Total Lesion Area 12 Weeks After the First Photodynamic Therapy (PDT)	-80.9 percentage of change from baseline Standard Deviation 27.65	-37.0 percentage of change from baseline Standard Deviation 39.86	-85.4 percentage of change from baseline Standard Deviation 22.81

SECONDARY outcome

Timeframe: 3-4 weeks after the second PDT, 15-16 weeks after first treatment

Population: ITT

the change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed 3-4 weeks after the second PDT. A second PDT was applied in case of non or partially responding lesions 12 weeks after first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=150 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=68 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=123 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Change From Baseline in Total Lesion Area 3-4 Weeks After the Second Photodynamic Therapy (PDT)	-87.5 percentage of change from baseline Standard Deviation 22.93	-46.2 percentage of change from baseline Standard Deviation 43.16	-91.4 percentage of change from baseline Standard Deviation 15.83

SECONDARY outcome

Timeframe: 12 weeks after the second PDT, 24 after first treatment

Population: ITT

the change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed 12 weeks after the second PDT. A second PDT was applied in case of non- or partially responding lesions 12 weeks after first PDT.

Outcome measures

Outcome measures
Measure	MAL Cream n=150 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=68 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=123 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Change From Baseline in Total Lesion Area 12 Weeks After Second Photodynamic Therapy (PDT)	-88.9 percentage of change from baseline Standard Deviation 19.03	-50.1 percentage of change from baseline Standard Deviation 43.89	-92.3 percentage of change from baseline Standard Deviation 17.15

SECONDARY outcome

Timeframe: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment

Population: ITT

the change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed at 3-4 weeks after last PDT, combining the changes from baseline in total lesion area of subjects 3-4 weeks after first PDT and second PDT (a second PDT was applied for subjects who showed non- or partially responding lesions 12 weeks after the first PDT).

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Change From Baseline in Total Lesion Area 3-4 Weeks After Last Photodynamic Therapy (PDT)	-86.6 percentage of change from baseline Standard Deviation 22.57	-43.8 percentage of change from baseline Standard Deviation 43.40	-89.4 percentage of change from baseline Standard Deviation 20.13

SECONDARY outcome

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

Population: ITT

the change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed at 12 weeks after last PDT, combining the changes from baseline in total lesion area at 12 weeks after the first PDT and at 12 weeks after the second PDT (a second PDT was applied to subjects with non- or partially responding lesions 12 weeks after the first PDT).

Outcome measures

Outcome measures
Measure	MAL Cream n=246 Participants Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. MAL: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	Vehicle n=76 Participants Topical application of BF-200 ALA matched placebo gel without active ingredient. Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA matched placebo: topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.	BF-200 ALA n=248 Participants Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. BF-200 ALA: topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
Change From Baseline in Total Lesion Area 12 Weeks After Last Photodynamic Therapy (PDT)	-92.0 percentage of change from baseline Standard Deviation 17.74	-48.5 percentage of change from baseline Standard Deviation 44.83	-95.0 percentage of change from baseline Standard Deviation 15.66

SECONDARY outcome

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

Population: ITT

The cosmetic outcome 12 weeks after the last PDT (12 weeks after 1st PDT for subjects who are completely cleared at this time point, 12 weeks after 2nd PDT for subjects retreated due to remaining lesions 12 weeks after 1st PDT) will be calculated on the basis of the skin quality assessment (skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring, and atrophy) upon visual examination (scale: 0= none, 1= mild, 2= moderate, 3=severe). The cosmetic outcome is 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; as good if the sum score has improved by at least 1 point as compared to baseline; as satisfactory if the sum score is identical to the one at baseline; as unsatisfactory if the sum score has worsened by 1 point compared to baseline and as impaired if the sum score has worsened by at least 2 points compared to baseline.