Clinical trial NCT02799069: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Actinic Keratosis
Lead sponsor: Biofrontera Bioscience GmbH
Sponsor class: INDUSTRY
Collaborators: name: Accovion GmbH
First posted: 2016-06-14
Enrollment: 571
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), ITT
timeFrame: 12 weeks after the last PDT, up to 24 weeks after the first treatment
measure: Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), PP
timeFrame: 12 weeks after the last PDT, up to 24 weeks after the first treatment
measure: Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only
timeFrame: 12 weeks after the last PDT, up to 24 weeks after the first treatment
Secondary outcomes:
measure: Percentage of Participants With Complete Response 3-4 Weeks After First Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the first PDT
measure: Percentage of Participants With Complete Response 12 Weeks After First Photodynamic Therapy (PDT)
timeFrame: 12 weeks after the first PDT
measure: Percentage of Participants With Complete Response 3-4 Weeks After the Second Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
measure: Percentage of Participants With Complete Response 12 Weeks After Second Photodynamic Therapy (PDT)
timeFrame: 12 weeks after the second PDT, 24 weeks after first treatment
measure: Percentage of Participants With Complete Response 3-4 Weeks After Last Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment
measure: Percentage of Participants With Partial Response at 3-4 Weeks After First Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the first PDT
measure: Percentage of Participants With Partial Response at 12 Weeks After the First Photodynamic Therapy (PDT)
timeFrame: 12 weeks after the first PDT
measure: Percentage of Participants With Partial Response at 3-4 Weeks After the Second Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
measure: Percentage of Participants With Partial Response at 12 Weeks After the Second Photodynamic Therapy (PDT)
timeFrame: 12 weeks after the second PDT, 24 weeks after first treatment
measure: Percentage of Participants With Partial Response at 3-4 Weeks After Last Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment
measure: Percentage of Participants With Partial Response at 12 Weeks After Last Photodynamic Therapy (PDT)
timeFrame: 12 weeks after the last PDT, up to 24 weeks after first treatment
measure: Complete Lesion Response Rate 3-4 Weeks After First Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the first PDT
measure: Complete Lesion Response Rate 12 Weeks After First Photodynamic Therapy (PDT)
timeFrame: 12 weeks after the first PDT
measure: Complete Lesion Response Rate 3-4 Weeks After the Second Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
measure: Complete Lesion Response Rate 12 Weeks After Second PDT
timeFrame: 12 weeks after the second PDT, 24 weeks after first treatment
measure: Complete Lesion Response Rate 3-4 Weeks After Last Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the last PDT, up to 16 weeks after first treatment
measure: Complete Lesion Response Rate 12 Weeks After Last Photodynamic Therapy (PDT)
timeFrame: 12 weeks after the last PDT, up to 24 weeks after first treatment
measure: Complete Lesion Response Rates 12 Weeks After Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only
timeFrame: up to 12 weeks after the last PDT, up to 24 weeks after first treatment
measure: Change From Baseline in Total Lesion Area 3-4 Weeks After the First Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the first PDT
measure: Change From Baseline in Total Lesion Area 12 Weeks After the First Photodynamic Therapy (PDT)
timeFrame: 12 weeks after the first PDT
measure: Change From Baseline in Total Lesion Area 3-4 Weeks After the Second Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
measure: Change From Baseline in Total Lesion Area 12 Weeks After Second Photodynamic Therapy (PDT)
timeFrame: 12 weeks after the second PDT, 24 after first treatment
measure: Change From Baseline in Total Lesion Area 3-4 Weeks After Last Photodynamic Therapy (PDT)
timeFrame: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment
measure: Change From Baseline in Total Lesion Area 12 Weeks After Last Photodynamic Therapy (PDT)
timeFrame: 12 weeks after the last PDT, up to 24 weeks after the first treatment
measure: Overall Cosmetic Outcome of the Treated Skin 12 Weeks After Last Photodynamic Therapy (PDT) Compared to Baseline
timeFrame: 12 weeks after the last PDT, up to 24 weeks after first treatment
measure: Local Skin Reactions During First Photodynamic Therapy (PDT-1)
timeFrame: during PDT treatment [3 h - 4 h ]
measure: Local Skin Reactions During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
timeFrame: during PDT treatment [3 h - 4 h ]
measure: Local Discomfort During First Photodynamic Therapy (PDT-1)
timeFrame: during PDT treatment [3 h - 4 h ]
measure: Local Discomfort During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
timeFrame: during PDT treatment [3 h - 4 h ]
measure: Local Discomfort - Pain During First Photodynamic Therapy (PDT-1)
timeFrame: during PDT treatment [3 h - 4 h ]
measure: Local Discomfort - Pain During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
timeFrame: during PDT treatment [3 h - 4 h ]
measure: Adverse Reactions
timeFrame: up to 12 weeks after the last PDT, up to 24 weeks after first treatment
Other outcomes:
Locations:
Study officials:
affiliation: Akademische Lehrpraxis der Universität Witten-Herdecke Heinz-Fangman-Straße 57 42287 Wuppertal
name: Thomas Dirschka, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.