Safety and Efficacy Study for the Field-directed Treatment of Actinic Keratosis (AK) With Photodynamic Therapy (PDT)

Phase 3

Completed

• Conditions: Actinic Keratosis
• Interventions: Drug: BF-200 ALA gel; Drug: Placebo to BF-200 ALA gel; Procedure: Photodynamic therapy with BF-RhodoLED

• Registration Number: NCT01966120
• Lead Sponsor: Biofrontera Bioscience GmbH

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of BF-200 ALA (Ameluz) versus placebo in the field-directed treatment of mild to moderate actinic keratosis with photodynamic therapy (PDT) when using the BF-RhodoLED lamp.

Detailed Description

The study was performed as a randomized, multicentre, double-blind, placebo- controlled, parallel-group, phase III trial with BF-200 ALA and placebo in seven centres in Germany. A total of 94 patients were screened in this study; 87 were randomized (55 patients received BF-200 ALA, 32 received placebo). Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Illumination was performed with the PDT lamp BF-RhodoLED.

Study Timeline

• Study Start: 2013-10
• Study First Submitted: 2013-10-17
• Study First Submitted QC: 2013-10-17
• Study First Posted: 2013-10-21
• Primary Completion: 2014-09
• Study Completion: 2015-04
• Results First Submitted: 2016-06-10
• Results First Submitted QC: 2016-10-26
• Results First Posted: 2016-12-19
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-20
• Last Update Posted: 2023-07-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 87

Inclusion Criteria

• Males or females between 18 and 85 years of age (inclusive)
• Presence of 4 to 8 clinically confirmed actinic keratosis (AK) target lesions of mild to moderate intensity within 1-2 fields

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Exclusion Criteria

• History of hypersensitivity to 5-ALA or any ingredient of BF-200 ALA
• Current treatment with immunosuppressive therapy
• Presence of other malignant or benign tumors of the skin within the treatment area (eg malignant melanoma, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)) within the last 4 weeks
• Confirmed diagnosis of SCC for the representative lesion by screening biopsy

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BF-200 ALA gel	BF-200 ALA gel	Photodynamic therapy with BF-RhodoLED in combination with BF-200 ALA.
Placebo to BF-200 ALA gel	Photodynamic therapy with BF-RhodoLED	Photodynamic therapy with BF-RhodoLED in combination with a nanoemulsion gel formulation similar to BF-200 ALA, but without the active ingredient 5-aminolevulinic acid.
BF-200 ALA gel	Photodynamic therapy with BF-RhodoLED	Photodynamic therapy with BF-RhodoLED in combination with BF-200 ALA.
Placebo to BF-200 ALA gel	Placebo to BF-200 ALA gel	Photodynamic therapy with BF-RhodoLED in combination with a nanoemulsion gel formulation similar to BF-200 ALA, but without the active ingredient 5-aminolevulinic acid.

Primary Outcome Measures

Name	Time	Method
Overall Patient Complete Response 12 Weeks After the Last PDT (PP)	12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT	All efficacy variables were evaluated for the FAS. The primary efficacy variable was also analyzed for the PP population. All subgroup analyses were carried out for the FAS. Data for size and grade of AK lesions were analyzed using the last observation carried forward (LOCF) approach, affecting the response rates evaluation.; Due to the small amount of missing data in the study, which did not have any relevant impact on primary results, sensitivity analyses for missing data were not performed.; The primary efficacy variable was the overall patient complete response 12 weeks after the last PDT. An overall complete responder was defined as a patient in whom all treated AK lesions were cleared (Olsen score of 0) after the last PDT, i.e. after PDT 1 or after PDT 2 if re-treatment was performed.
Overall Patient Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT)	12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT	All efficacy variables were evaluated for the FAS. The primary efficacy variable was also analyzed for the PP population. All subgroup analyses were carried out for the FAS. Data for size and grade of AK lesions were analyzed using the last observation carried forward (LOCF) approach, affecting the response rates evaluation.; Due to the small amount of missing data in the study, which did not have any relevant impact on primary results, sensitivity analyses for missing data were not performed.; The primary efficacy variable was the overall patient complete response 12 weeks after the last PDT. An overall complete responder was defined as a patient in whom all treated actinic keratosis (AK) lesions were cleared (Olsen score of 0) after the last PDT, i.e. after PDT 1 or after PDT 2 if re-treatment was performed.

Secondary Outcome Measures

Name	Time	Method
Change of Total Lesion Area 12 Weeks After Last PDT	12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT	The fifth key secondary efficacy variable in the hierarchic test procedure was the change from baseline in the total lesion area per patient assessed at 12 weeks after last PDT.
Patient Histopathological Confirmed Response Rate	12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT	For the secondary confirmatory analysis, several superiority hypotheses were tested within a pre-defined hierarchic multiple testing procedure as described in the Statistical Analysis Protocoll (SAP).; The key secondary efficacy variables were tested strictly in a pre-defined order to ensure the family-wise error rate (FWER) and the testing procedure had to be stopped once the first non-significant test was obtained.; The results of the confirmatory analysis are presented in the order pre-defined by the confirmatory testing procedure.; Assessments of the patient histopathological confirmed response (HCR) rates were based on the results from the biopsy taken 12 weeks after the last PDT from a representative AK lesion selected at screening. If the biopsy result for a patient revealed a residual AK, the patient was considered "not cleared" for the analysis irrespectively of the investigator's clinical assessment.
Patient Complete Response 12 Weeks After PDT 1	12 weeks after PDT 1	The second key secondary efficacy variable in the hierarchic test procedure was the patient complete response (complete clearance of all treated AK lesions) assessed at 12 weeks after PDT 1.
Lesion Complete Response 12 Weeks After Last PDT	12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT	The third key secondary efficacy variable in the hierarchic test procedure was the lesion complete response (completely cleared individual AK lesions) assessed at 12 weeks after last PDT.
Patient Partial Response 12 Weeks After Last PDT	12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT	The fourth key secondary efficacy variable in the hierarchic test procedure was the patient partial response (defined as complete clearance of at least 75% of treated AK lesions) assessed at 12 weeks after last PDT.
Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3	12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT	Study personnel assessed and recorded the skin quality of the treated field(s) at baseline and at the end-of-study visit including skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring and atrophy.; Upon visual examination of the treated field(s), the investigator coded the intensity of each skin parameter on a scale of 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.; The cosmetic outcome evaluations were based on the sum score of the skin quality assessment (sum of all ratings for each skin parameter) at the end-of-study visit (Visit 4 or Visit 6, if retreated).; The outcome was calculated using a 5-point scale ranging from "very good" (0) to "impaired" (4) based on the change of the skin quality assessments compared to baseline (0 = 2 points improvement; 1 = 1 point improvement; 2 = no change; 3 = 1 point worsened; 4 = at least 2 points worsened).
Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 1 to 3	12 weeks after PDT 1 or 12 weeks after PDT 2 which might have been necessary because not all lesions were cleared after the first PDT	Study personnel assessed and recorded the skin quality of the treated field(s) at baseline and at the end-of-study visit including skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring and atrophy.; Upon visual examination of the treated field(s), the investigator coded the intensity of each skin parameter on a scale of 0 to 3, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.; The cosmetic outcome evaluations were based on the sum score of the skin quality assessment (sum of all ratings for each skin parameter) at the end-of-study visit (Visit 4 or Visit 6, if retreated).; The outcome was calculated using a 5-point scale ranging from "very good" (0) to "impaired" (4) based on the change of the skin quality assessments compared to baseline (0 = 2 points improvement; 1 = 1 point improvement; 2 = no change; 3 = 1 point worsened; 4 = at least 2 points worsened).

Trial Locations

Locations (1)

Dermatologisches Zentrum Bonn Friedensplatz; 🇩🇪 Bonn, Germany