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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biofrontera Bioscience GmbH
ClinicalTrials.gov Identifier:
NCT01966120
First received: October 17, 2013
Last updated: October 26, 2016
Last verified: October 2016
  Purpose
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.

Condition Intervention Phase
Actinic Keratosis
Drug: BF-200 ALA gel
Drug: Placebo to BF-200 ALA gel
Procedure: Photodynamic therapy with BF-RhodoLED
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Phase III, Multi-center Study 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

Resource links provided by NLM:


Further study details as provided by Biofrontera Bioscience GmbH:

Primary Outcome Measures:
  • Overall Patient Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT) [ Time Frame: 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.


  • Overall Patient Complete Response 12 Weeks After the Last PDT (PP) [ Time Frame: 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.



Secondary Outcome Measures:
  • Patient Histopathological Confirmed Response Rate [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

  • Change of Total Lesion Area 12 Weeks After Last PDT [ Time Frame: 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.

  • Overall Cosmetic Outcome 12 Weeks After Last PDT for Patients With Sum Score at Baseline of 0 to 3 [ Time Frame: 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 [ Time Frame: 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).



Enrollment: 87
Study Start Date: October 2013
Study Completion Date: April 2015
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: BF-200 ALA gel
Photodynamic therapy with BF-RhodoLED in combination with BF-200 ALA.
Drug: BF-200 ALA gel
BF-200 ALA was applied over 1-2 fields of approximately 20 cm² in total, allowed to dry for approximately 10 minutes, and covered with occlusive tape material for 3 h.
Other Name: Ameluz
Procedure: Photodynamic therapy with BF-RhodoLED
After cleaning the lesions, the entire treatment field(s) were illuminated using the novel narrow spectrum BF-RhodoLED lamp, a red light illumination source (approximately 635 nm) developed by Biofrontera, until a total light dose of 37 J/cm² (per treated field) was achieved.
Other Name: PDT
Placebo Comparator: 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.
Drug: Placebo to BF-200 ALA gel
The reference product was a placebo (a nanoemulsion gel formulation similar to the Investigational Medicinal Product (IMP), but without the active ingredient). The placebo was packaged, assigned to each patient, and administered in the same way as the IMP.
Procedure: Photodynamic therapy with BF-RhodoLED
After cleaning the lesions, the entire treatment field(s) were illuminated using the novel narrow spectrum BF-RhodoLED lamp, a red light illumination source (approximately 635 nm) developed by Biofrontera, until a total light dose of 37 J/cm² (per treated field) was achieved.
Other Name: PDT

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.
  Eligibility

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01966120

Locations
Germany
Dermatologisches Zentrum Bonn Friedensplatz
Bonn, Germany
Sponsors and Collaborators
Biofrontera Bioscience GmbH
Investigators
Principal Investigator: Uwe Reinhold, Prof. Dr. Dermatologisches Zentrum Bonn
  More Information

Responsible Party: Biofrontera Bioscience GmbH
ClinicalTrials.gov Identifier: NCT01966120     History of Changes
Other Study ID Numbers: ALA-AK-CT007  2013-002510-12 
Study First Received: October 17, 2013
Results First Received: June 10, 2016
Last Updated: October 26, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Biofrontera Bioscience GmbH:
Photodynamic Therapy
Field-directed Treatment

Additional relevant MeSH terms:
Keratosis
Keratosis, Actinic
Skin Diseases
Precancerous Conditions
Neoplasms
Aminolevulinic Acid
Photosensitizing Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on February 17, 2017