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

Primary Purpose

Actinic Keratosis

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
BF-200 ALA
MAL Cream
Vehicle
Sponsored by
Biofrontera Bioscience GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Actinic Keratosis

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Main Inclusion Criteria:

  • Written informed consent.
  • Men and women between 18 and 85 years of age.
  • 4-8 AK lesions of 0.5 to 1.5 cm diameter of mild to moderate intensity (Olsen grade 1 and 2) in the face and/or on the bald scalp. Lesions on the eyes, nostrils, ears and mouth were not considered for treatment during the planned study.
  • Target AK lesions were to be discrete and quantifiable; adjacent AK lesions were to show a minimum distance of 1.0 cm from one another.
  • Confirmation of AK by biopsy taken at screening.
  • Free of significant physical abnormalities (e.g., tattoos, dermatoses) in the potential treatment region that could have caused difficulty with examination or final evaluation.
  • Willingness to stop the use of moisturizers and any other topical treatments within the treatment region.
  • Good general health condition.
  • Healthy subjects and subjects with clinically stable medical conditions including, but not limited to the following diseases (controlled hypertension, diabetes mellitus type II, hypercholesterolemia, osteoarthritis) were permitted to be included in the study if the medication taken for the treatment of the disease did not match an exclusion criterion or was not specified as prohibited concomitant medication.
  • No extensive sunbathing or solarium use during the trial.
  • Negative pregnancy test at screening.

Main exclusion criteria:

  • Known hypersensitivity to BF-200 ALA, MAL (methyl-aminolevulinic acid) and/or any of the ingredients of the formulations
  • Clinically significant medical conditions (tumor disease etc.) making implementation of the protocol or interpretation of the study results difficult
  • Presence of photodermatoses
  • Presence of other tumors in the treatment areas within the last 4 weeks
  • Start of treatment with phototoxic or photoallergic drugs within 8 weeks prior to screening
  • Current treatment with immunosuppression therapy
  • Hypersensitivity to porphyrins
  • Presence of porphyria
  • Presence of inherited or acquired coagulation defect
  • Any topical treatment within the treatment area within 12 weeks before PDT1 (first PDT Treatment)
  • Topical treatment with ALA or MAL outside the treatment area during participation in the study
  • None of the specified systemic treatments within the designated period before PDT1

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Active Comparator

    Active Comparator

    Placebo Comparator

    Arm Label

    BF-200 ALA

    MAL Cream

    Vehicle

    Arm Description

    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.

    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.

    Topical application of matched Placebo to BF-200 ALA gel (without containing active ingredient) ). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), 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)
    Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), 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)
    Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only
    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)

    Secondary Outcome Measures

    Percentage of Participants With Complete Response 3-4 Weeks After First Photodynamic Therapy (PDT)
    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.
    Percentage of Participants With Complete Response 12 Weeks After First Photodynamic Therapy (PDT)
    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.
    Percentage of Participants With Complete Response 3-4 Weeks After the Second Photodynamic Therapy (PDT)
    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.
    Percentage of Participants With Complete Response 12 Weeks After Second Photodynamic Therapy (PDT)
    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.
    Percentage of Participants With Complete Response 3-4 Weeks After Last Photodynamic Therapy (PDT)
    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).
    Percentage of Participants With Partial Response at 3-4 Weeks After First Photodynamic Therapy (PDT)
    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.
    Percentage of Participants With Partial Response at 12 Weeks After the First Photodynamic Therapy (PDT)
    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.
    Percentage of Participants With Partial Response at 3-4 Weeks After the Second Photodynamic Therapy (PDT)
    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.
    Percentage of Participants With Partial Response at 12 Weeks After the Second Photodynamic Therapy (PDT)
    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.
    Percentage of Participants With Partial Response at 3-4 Weeks After Last Photodynamic Therapy (PDT)
    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).
    Percentage of Participants With Partial Response at 12 Weeks After Last Photodynamic Therapy (PDT)
    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) .
    Complete Lesion Response Rate 3-4 Weeks After First Photodynamic Therapy (PDT)
    Completely cleared individual lesions as defined at 3-4 weeks after first photodynamic therapy (PDT)
    Complete Lesion Response Rate 12 Weeks After First Photodynamic Therapy (PDT)
    Completely cleared individual lesions as defined at 12 weeks after the first photodynamic therapy (PDT).
    Complete Lesion Response Rate 3-4 Weeks After the Second Photodynamic Therapy (PDT)
    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.
    Complete Lesion Response Rate 12 Weeks After Second PDT
    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.
    Complete Lesion Response Rate 3-4 Weeks After Last Photodynamic Therapy (PDT)
    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).
    Complete Lesion Response Rate 12 Weeks After Last Photodynamic Therapy (PDT)
    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).
    Complete Lesion Response Rates 12 Weeks After Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only
    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).
    Change From Baseline in Total Lesion Area 3-4 Weeks After the First Photodynamic Therapy (PDT)
    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.
    Change From Baseline in Total Lesion Area 12 Weeks After the First Photodynamic Therapy (PDT)
    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.
    Change From Baseline in Total Lesion Area 3-4 Weeks After the Second Photodynamic Therapy (PDT)
    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.
    Change From Baseline in Total Lesion Area 12 Weeks After Second Photodynamic Therapy (PDT)
    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.
    Change From Baseline in Total Lesion Area 3-4 Weeks After Last Photodynamic Therapy (PDT)
    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).
    Change From Baseline in Total Lesion Area 12 Weeks After Last Photodynamic Therapy (PDT)
    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).
    Overall Cosmetic Outcome of the Treated Skin 12 Weeks After Last Photodynamic Therapy (PDT) Compared to Baseline
    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.
    Local Skin Reactions During First Photodynamic Therapy (PDT-1)
    Local skin reactions in the treatment area as assessed by the investigator during the first PDT (PDT-1)
    Local Skin Reactions During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
    Local skin reactions in the treatment area as assessed by the investigator during PDT-2; only applicable for subjects who were retreated with a second PDT due to remaining lesions 12 weeks after the first PDT (subjects with data).
    Local Discomfort During First Photodynamic Therapy (PDT-1)
    Local discomfort reported by the patients during Illumination of first PDT (PDT1)
    Local Discomfort During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
    Local discomfort reported by the patients during Illumination phase of retreatment (PDT-2); only applicable for subjects who received a retreatment (PDT-2) due to remaining lesions 12 weeks after the first treatment (PDT-1) (subjects with data)
    Local Discomfort - Pain During First Photodynamic Therapy (PDT-1)
    Pain (11-point numeric rating scale) by PDT Session; Overall (If both areas have been treated, maximum intensity over both areas is used for analysis.) Patients assessed the pain experienced during PDT using an 11-point numeric rating pain scale (NRPS) ranging from 0 (no pain at all) to 10 (worst possible pain). This score reflects the patient's maximum pain during PDT. This outcome measure shows pain score after the first PDT.
    Local Discomfort - Pain During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
    Pain (11-point numeric rating scale) by PDT Session; Overall (If both areas have been treated, maximum intensity over both areas is used for analysis.) Patients assessed the pain experienced during PDT using an 11-point numeric rating pain scale (NRPS) ranging from 0 (no pain at all) to 10 (worst possible pain). This score reflects the patient's maximum pain during PDT. Only applicable for subjects who received a retreatment (PDT-2) due to remaining lesions 12 weeks after the first treatment (PDT-1) (subjects with data)
    Adverse Reactions
    Adverse reactions are Treatment-Emergent Adverse Events considered at least possibly related to the treatment with the randomized investigational medicinal products; Adverse reactions are shown with a frequency cut off of >=5%. TEAEs are considered from subjects who received only one PDT or subjects who received 2 PDTs (initial Treatment (PDT-1) and retreatment (PDT-2) due to remaining lesions 12 weeks after first photodynamic therapy. The safety set consists of all patients treated at least once with investigational product. Treatment with investigational product consists of application of study drug followed by illumination. This excludes one patient from the safety set; for this patient the investigational product was applied on the skin but it was not illuminated. Patients are treated according to actual treatment.

    Full Information

    First Posted
    May 26, 2016
    Last Updated
    March 28, 2017
    Sponsor
    Biofrontera Bioscience GmbH
    Collaborators
    Accovion GmbH
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02799069
    Brief Title
    Evaluation of Safety and Efficacy of BF-200 ALA for the Treatment of Actinic Keratosis With Photodynamic Therapy
    Official Title
    A Randomized, Observer Blind, Multinational Phase III Study to Evaluate the Safety and Efficacy of a Nanoemulsion Gel Formulation BF-200 ALA, in Comparison With Metvix® and Placebo, for the Treatment of Actinic Keratosis With PDT
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    April 2008 (undefined)
    Primary Completion Date
    August 2009 (Actual)
    Study Completion Date
    August 2009 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Biofrontera Bioscience GmbH
    Collaborators
    Accovion GmbH

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The aim of the study is to evaluate the non-inferiority of BF-200 ALA (Ameluz) in the treatment of actinic keratosis (AK) with photodynamic therapy (PDT) compared to Metvix.
    Detailed Description
    This was a randomized, observer-blind, multinational, comparator and placebo-controlled parallel group, (3:3:1 ratio) study to compare the efficacy and safety of BF-200 ALA with the comparator Metvix® (methyl-[5-amino-4-oxopentanoate]) and placebo, for the treatment of AK with PDT.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Actinic Keratosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    Outcomes Assessor
    Allocation
    Randomized
    Enrollment
    571 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    BF-200 ALA
    Arm Type
    Active Comparator
    Arm Description
    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.
    Arm Title
    MAL Cream
    Arm Type
    Active Comparator
    Arm Description
    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.
    Arm Title
    Vehicle
    Arm Type
    Placebo Comparator
    Arm Description
    Topical application of matched Placebo to BF-200 ALA gel (without containing active ingredient) ). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin.
    Intervention Type
    Drug
    Intervention Name(s)
    BF-200 ALA
    Other Intervention Name(s)
    Ameluz
    Intervention Description
    topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
    Intervention Type
    Drug
    Intervention Name(s)
    MAL Cream
    Other Intervention Name(s)
    Metvix, Metvixia
    Intervention Description
    topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
    Intervention Type
    Drug
    Intervention Name(s)
    Vehicle
    Other Intervention Name(s)
    matched placebo to BF-200 ALA gel
    Intervention Description
    topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
    Primary Outcome Measure Information:
    Title
    Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), ITT
    Description
    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)
    Time Frame
    12 weeks after the last PDT, up to 24 weeks after the first treatment
    Title
    Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), PP
    Description
    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)
    Time Frame
    12 weeks after the last PDT, up to 24 weeks after the first treatment
    Title
    Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only
    Description
    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)
    Time Frame
    12 weeks after the last PDT, up to 24 weeks after the first treatment
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants With Complete Response 3-4 Weeks After First Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    3-4 weeks after the first PDT
    Title
    Percentage of Participants With Complete Response 12 Weeks After First Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    12 weeks after the first PDT
    Title
    Percentage of Participants With Complete Response 3-4 Weeks After the Second Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    3-4 weeks after the second PDT, 15-16 weeks after first treatment
    Title
    Percentage of Participants With Complete Response 12 Weeks After Second Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    12 weeks after the second PDT, 24 weeks after first treatment
    Title
    Percentage of Participants With Complete Response 3-4 Weeks After Last Photodynamic Therapy (PDT)
    Description
    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).
    Time Frame
    3-4 weeks after the last PDT, up to 16 weeks after the first treatment
    Title
    Percentage of Participants With Partial Response at 3-4 Weeks After First Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    3-4 weeks after the first PDT
    Title
    Percentage of Participants With Partial Response at 12 Weeks After the First Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    12 weeks after the first PDT
    Title
    Percentage of Participants With Partial Response at 3-4 Weeks After the Second Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    3-4 weeks after the second PDT, 15-16 weeks after first treatment
    Title
    Percentage of Participants With Partial Response at 12 Weeks After the Second Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    12 weeks after the second PDT, 24 weeks after first treatment
    Title
    Percentage of Participants With Partial Response at 3-4 Weeks After Last Photodynamic Therapy (PDT)
    Description
    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).
    Time Frame
    3-4 weeks after the last PDT, up to 16 weeks after the first treatment
    Title
    Percentage of Participants With Partial Response at 12 Weeks After Last Photodynamic Therapy (PDT)
    Description
    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) .
    Time Frame
    12 weeks after the last PDT, up to 24 weeks after first treatment
    Title
    Complete Lesion Response Rate 3-4 Weeks After First Photodynamic Therapy (PDT)
    Description
    Completely cleared individual lesions as defined at 3-4 weeks after first photodynamic therapy (PDT)
    Time Frame
    3-4 weeks after the first PDT
    Title
    Complete Lesion Response Rate 12 Weeks After First Photodynamic Therapy (PDT)
    Description
    Completely cleared individual lesions as defined at 12 weeks after the first photodynamic therapy (PDT).
    Time Frame
    12 weeks after the first PDT
    Title
    Complete Lesion Response Rate 3-4 Weeks After the Second Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    3-4 weeks after the second PDT, 15-16 weeks after first treatment
    Title
    Complete Lesion Response Rate 12 Weeks After Second PDT
    Description
    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.
    Time Frame
    12 weeks after the second PDT, 24 weeks after first treatment
    Title
    Complete Lesion Response Rate 3-4 Weeks After Last Photodynamic Therapy (PDT)
    Description
    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).
    Time Frame
    3-4 weeks after the last PDT, up to 16 weeks after first treatment
    Title
    Complete Lesion Response Rate 12 Weeks After Last Photodynamic Therapy (PDT)
    Description
    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).
    Time Frame
    12 weeks after the last PDT, up to 24 weeks after first treatment
    Title
    Complete Lesion Response Rates 12 Weeks After Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only
    Description
    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).
    Time Frame
    up to 12 weeks after the last PDT, up to 24 weeks after first treatment
    Title
    Change From Baseline in Total Lesion Area 3-4 Weeks After the First Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    3-4 weeks after the first PDT
    Title
    Change From Baseline in Total Lesion Area 12 Weeks After the First Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    12 weeks after the first PDT
    Title
    Change From Baseline in Total Lesion Area 3-4 Weeks After the Second Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    3-4 weeks after the second PDT, 15-16 weeks after first treatment
    Title
    Change From Baseline in Total Lesion Area 12 Weeks After Second Photodynamic Therapy (PDT)
    Description
    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.
    Time Frame
    12 weeks after the second PDT, 24 after first treatment
    Title
    Change From Baseline in Total Lesion Area 3-4 Weeks After Last Photodynamic Therapy (PDT)
    Description
    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).
    Time Frame
    3-4 weeks after the last PDT, up to 16 weeks after the first treatment
    Title
    Change From Baseline in Total Lesion Area 12 Weeks After Last Photodynamic Therapy (PDT)
    Description
    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).
    Time Frame
    12 weeks after the last PDT, up to 24 weeks after the first treatment
    Title
    Overall Cosmetic Outcome of the Treated Skin 12 Weeks After Last Photodynamic Therapy (PDT) Compared to Baseline
    Description
    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.
    Time Frame
    12 weeks after the last PDT, up to 24 weeks after first treatment
    Title
    Local Skin Reactions During First Photodynamic Therapy (PDT-1)
    Description
    Local skin reactions in the treatment area as assessed by the investigator during the first PDT (PDT-1)
    Time Frame
    during PDT treatment [3 h - 4 h ]
    Title
    Local Skin Reactions During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
    Description
    Local skin reactions in the treatment area as assessed by the investigator during PDT-2; only applicable for subjects who were retreated with a second PDT due to remaining lesions 12 weeks after the first PDT (subjects with data).
    Time Frame
    during PDT treatment [3 h - 4 h ]
    Title
    Local Discomfort During First Photodynamic Therapy (PDT-1)
    Description
    Local discomfort reported by the patients during Illumination of first PDT (PDT1)
    Time Frame
    during PDT treatment [3 h - 4 h ]
    Title
    Local Discomfort During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
    Description
    Local discomfort reported by the patients during Illumination phase of retreatment (PDT-2); only applicable for subjects who received a retreatment (PDT-2) due to remaining lesions 12 weeks after the first treatment (PDT-1) (subjects with data)
    Time Frame
    during PDT treatment [3 h - 4 h ]
    Title
    Local Discomfort - Pain During First Photodynamic Therapy (PDT-1)
    Description
    Pain (11-point numeric rating scale) by PDT Session; Overall (If both areas have been treated, maximum intensity over both areas is used for analysis.) Patients assessed the pain experienced during PDT using an 11-point numeric rating pain scale (NRPS) ranging from 0 (no pain at all) to 10 (worst possible pain). This score reflects the patient's maximum pain during PDT. This outcome measure shows pain score after the first PDT.
    Time Frame
    during PDT treatment [3 h - 4 h ]
    Title
    Local Discomfort - Pain During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
    Description
    Pain (11-point numeric rating scale) by PDT Session; Overall (If both areas have been treated, maximum intensity over both areas is used for analysis.) Patients assessed the pain experienced during PDT using an 11-point numeric rating pain scale (NRPS) ranging from 0 (no pain at all) to 10 (worst possible pain). This score reflects the patient's maximum pain during PDT. Only applicable for subjects who received a retreatment (PDT-2) due to remaining lesions 12 weeks after the first treatment (PDT-1) (subjects with data)
    Time Frame
    during PDT treatment [3 h - 4 h ]
    Title
    Adverse Reactions
    Description
    Adverse reactions are Treatment-Emergent Adverse Events considered at least possibly related to the treatment with the randomized investigational medicinal products; Adverse reactions are shown with a frequency cut off of >=5%. TEAEs are considered from subjects who received only one PDT or subjects who received 2 PDTs (initial Treatment (PDT-1) and retreatment (PDT-2) due to remaining lesions 12 weeks after first photodynamic therapy. The safety set consists of all patients treated at least once with investigational product. Treatment with investigational product consists of application of study drug followed by illumination. This excludes one patient from the safety set; for this patient the investigational product was applied on the skin but it was not illuminated. Patients are treated according to actual treatment.
    Time Frame
    up to 12 weeks after the last PDT, up to 24 weeks after first treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    85 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Main Inclusion Criteria: Written informed consent. Men and women between 18 and 85 years of age. 4-8 AK lesions of 0.5 to 1.5 cm diameter of mild to moderate intensity (Olsen grade 1 and 2) in the face and/or on the bald scalp. Lesions on the eyes, nostrils, ears and mouth were not considered for treatment during the planned study. Target AK lesions were to be discrete and quantifiable; adjacent AK lesions were to show a minimum distance of 1.0 cm from one another. Confirmation of AK by biopsy taken at screening. Free of significant physical abnormalities (e.g., tattoos, dermatoses) in the potential treatment region that could have caused difficulty with examination or final evaluation. Willingness to stop the use of moisturizers and any other topical treatments within the treatment region. Good general health condition. Healthy subjects and subjects with clinically stable medical conditions including, but not limited to the following diseases (controlled hypertension, diabetes mellitus type II, hypercholesterolemia, osteoarthritis) were permitted to be included in the study if the medication taken for the treatment of the disease did not match an exclusion criterion or was not specified as prohibited concomitant medication. No extensive sunbathing or solarium use during the trial. Negative pregnancy test at screening. Main exclusion criteria: Known hypersensitivity to BF-200 ALA, MAL (methyl-aminolevulinic acid) and/or any of the ingredients of the formulations Clinically significant medical conditions (tumor disease etc.) making implementation of the protocol or interpretation of the study results difficult Presence of photodermatoses Presence of other tumors in the treatment areas within the last 4 weeks Start of treatment with phototoxic or photoallergic drugs within 8 weeks prior to screening Current treatment with immunosuppression therapy Hypersensitivity to porphyrins Presence of porphyria Presence of inherited or acquired coagulation defect Any topical treatment within the treatment area within 12 weeks before PDT1 (first PDT Treatment) Topical treatment with ALA or MAL outside the treatment area during participation in the study None of the specified systemic treatments within the designated period before PDT1
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Thomas Dirschka, Prof. Dr.
    Organizational Affiliation
    Akademische Lehrpraxis der Universität Witten-Herdecke Heinz-Fangman-Straße 57 42287 Wuppertal
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    21910711
    Citation
    Dirschka T, Radny P, Dominicus R, Mensing H, Bruning H, Jenne L, Karl L, Sebastian M, Oster-Schmidt C, Klovekorn W, Reinhold U, Tanner M, Grone D, Deichmann M, Simon M, Hubinger F, Hofbauer G, Krahn-Senftleben G, Borrosch F, Reich K, Berking C, Wolf P, Lehmann P, Moers-Carpi M, Honigsmann H, Wernicke-Panten K, Helwig C, Foguet M, Schmitz B, Lubbert H, Szeimies RM; AK-CT002 Study Group. Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo. Br J Dermatol. 2012 Jan;166(1):137-46. doi: 10.1111/j.1365-2133.2011.10613.x. Epub 2011 Dec 21.
    Results Reference
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    PubMed Identifier
    23252768
    Citation
    Dirschka T, Radny P, Dominicus R, Mensing H, Bruning H, Jenne L, Karl L, Sebastian M, Oster-Schmidt C, Klovekorn W, Reinhold U, Tanner M, Grone D, Deichmann M, Simon M, Hubinger F, Hofbauer G, Krahn-Senftleben G, Borrosch F, Reich K, Berking C, Wolf P, Lehmann P, Moers-Carpi M, Honigsmann H, Wernicke-Panten K, Hahn S, Pabst G, Voss D, Foguet M, Schmitz B, Lubbert H, Szeimies RM; AK-CT002 Study Group; AK-CT003 Study Group. Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis. Br J Dermatol. 2013 Apr;168(4):825-36. doi: 10.1111/bjd.12158.
    Results Reference
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    Learn more about this trial

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

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