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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 571
- 主要终点
- Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), PP
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: BF-200 ALA (Drug)
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.
干预措施: MAL Cream (Drug)
Vehicle
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.
干预措施: Vehicle (Drug)
结局指标
主要结局
Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), PP
时间窗: 12 weeks after the last PDT, up to 24 weeks after the first treatment
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), ITT
时间窗: 12 weeks after the last PDT, up to 24 weeks after the first treatment
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
时间窗: 12 weeks after the last PDT, up to 24 weeks after the first treatment
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)
次要结局
- Complete Lesion Response Rate 3-4 Weeks After the Second Photodynamic Therapy (PDT)(3-4 weeks after the second PDT, 15-16 weeks after first treatment)
- Percentage of Participants With Complete Response 3-4 Weeks After First Photodynamic Therapy (PDT)(3-4 weeks after the first PDT)
- Percentage of Participants With Partial Response at 3-4 Weeks After First Photodynamic Therapy (PDT)(3-4 weeks after the first PDT)
- Change From Baseline in Total Lesion Area 12 Weeks After the First Photodynamic Therapy (PDT)(12 weeks after the first PDT)
- Percentage of Participants With Complete Response 12 Weeks After Second Photodynamic Therapy (PDT)(12 weeks after the second PDT, 24 weeks after first treatment)
- Percentage of Participants With Partial Response at 12 Weeks After the First Photodynamic Therapy (PDT)(12 weeks after the first PDT)
- Percentage of Participants With Partial Response at 3-4 Weeks After the Second Photodynamic Therapy (PDT)(3-4 weeks after the second PDT, 15-16 weeks after first treatment)
- Complete Lesion Response Rate 12 Weeks After First Photodynamic Therapy (PDT)(12 weeks after the first PDT)
- Complete Lesion Response Rate 12 Weeks After Second PDT(12 weeks after the second PDT, 24 weeks after first treatment)
- Complete Lesion Response Rate 12 Weeks After Last Photodynamic Therapy (PDT)(12 weeks after the last PDT, up to 24 weeks after first treatment)
- Percentage of Participants With Complete Response 3-4 Weeks After the Second Photodynamic Therapy (PDT)(3-4 weeks after the second PDT, 15-16 weeks after first treatment)
- Percentage of Participants With Partial Response at 12 Weeks After the Second Photodynamic Therapy (PDT)(12 weeks after the second PDT, 24 weeks after first treatment)
- Percentage of Participants With Partial Response at 12 Weeks After Last Photodynamic Therapy (PDT)(12 weeks after the last PDT, up to 24 weeks after first treatment)
- Change From Baseline in Total Lesion Area 12 Weeks After Second Photodynamic Therapy (PDT)(12 weeks after the second PDT, 24 after first treatment)
- Change From Baseline in Total Lesion Area 3-4 Weeks After Last Photodynamic Therapy (PDT)(3-4 weeks after the last PDT, up to 16 weeks after the first treatment)
- Change From Baseline in Total Lesion Area 3-4 Weeks After the Second Photodynamic Therapy (PDT)(3-4 weeks after the second PDT, 15-16 weeks after first treatment)
- Local Skin Reactions During Second Photodynamic Therapy (PDT-2) for Retreated Subjects(during PDT treatment [3 h - 4 h ])
- Local Discomfort During Second Photodynamic Therapy (PDT-2) for Retreated Subjects(during PDT treatment [3 h - 4 h ])
- Overall Cosmetic Outcome of the Treated Skin 12 Weeks After Last Photodynamic Therapy (PDT) Compared to Baseline(12 weeks after the last PDT, up to 24 weeks after first treatment)
- Local Discomfort - Pain During Second Photodynamic Therapy (PDT-2) for Retreated Subjects(during PDT treatment [3 h - 4 h ])
- Adverse Reactions(up to 12 weeks after the last PDT, up to 24 weeks after first treatment)
- Change From Baseline in Total Lesion Area 12 Weeks After Last Photodynamic Therapy (PDT)(12 weeks after the last PDT, up to 24 weeks after the first treatment)
- Local Skin Reactions During First Photodynamic Therapy (PDT-1)(during PDT treatment [3 h - 4 h ])
- Local Discomfort During First Photodynamic Therapy (PDT-1)(during PDT treatment [3 h - 4 h ])
- Local Discomfort - Pain During First Photodynamic Therapy (PDT-1)(during PDT treatment [3 h - 4 h ])
- Percentage of Participants With Complete Response 12 Weeks After First Photodynamic Therapy (PDT)(12 weeks after the first PDT)
- Percentage of Participants With Complete Response 3-4 Weeks After Last Photodynamic Therapy (PDT)(3-4 weeks after the last PDT, up to 16 weeks after the first treatment)
- Percentage of Participants With Partial Response at 3-4 Weeks After Last Photodynamic Therapy (PDT)(3-4 weeks after the last PDT, up to 16 weeks after the first treatment)
- Complete Lesion Response Rate 3-4 Weeks After First Photodynamic Therapy (PDT)(3-4 weeks after the first PDT)
- Complete Lesion Response Rate 3-4 Weeks After Last Photodynamic Therapy (PDT)(3-4 weeks after the last PDT, up to 16 weeks after first treatment)
- Complete Lesion Response Rates 12 Weeks After Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only(up to 12 weeks after the last PDT, up to 24 weeks after first treatment)
- Change From Baseline in Total Lesion Area 3-4 Weeks After the First Photodynamic Therapy (PDT)(3-4 weeks after the first PDT)