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

NCT01966120 | Completed Phase 3 Results

• 2 other identifiers: ALA-AK-CT0072013-002510-12
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

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.

Conditions

Actinic Keratosis

Keywords

Photodynamic Therapy; Field-directed Treatment

Outcome Measures

Primary Outcomes (2)

• Overall Patient Complete Response 12 Weeks After the Last Photodynamic Therapy (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.

  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

• Overall Patient Complete Response 12 Weeks After the Last PDT (PP)

  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.

  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

Secondary Outcomes (7)

• 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

• Patient Complete Response 12 Weeks After PDT 1

  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

• 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

• 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

Other Outcomes (6)

• Patient Recurrence Rate in Follow-up (Cumulative)

  12 months after last treatment (PDT-1 or PDT-2, if re-treated)

• Lesion Recurrence Rate in Follow-up (Cumulative)

  12 months after last treatment (PDT-1 or PDT-2, if retreated)

• Skin Quality in Follow-up (6 Months)

  6 months after last treatment (PDT-1 or PDT-2, if re-treated)

Study Arms (2)

BF-200 ALA gel

ACTIVE COMPARATOR

Photodynamic therapy with BF-RhodoLED in combination with BF-200 ALA.

Drug: BF-200 ALA gel; Procedure: Photodynamic therapy with BF-RhodoLED

Placebo to BF-200 ALA gel

PLACEBO COMPARATOR

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; Procedure: Photodynamic therapy with BF-RhodoLED

Interventions

BF-200 ALA gel DRUG

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.

Also known as: Ameluz

BF-200 ALA gel

Placebo to BF-200 ALA gel DRUG

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.

Placebo to BF-200 ALA gel

Photodynamic therapy with BF-RhodoLED PROCEDURE

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.

Also known as: PDT

BF-200 ALA gel; Placebo to BF-200 ALA gel

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biofrontera Bioscience GmbH: lead

Study Sites (1)

Dermatologisches Zentrum Bonn Friedensplatz

Bonn, Germany

Location

Related Publications (1)

• Reinhold U, Philipp-Dormston WG, Dirschka T, Ostendorf R, Aschoff R, Berking C, Jager A, Schmitz B, Foguet M, Szeimies RM. Long-term follow-up of a randomized, double-blind, phase III, multi-centre study to evaluate the safety and efficacy of field-directed photodynamic therapy (PDT) of mild to moderate actinic keratosis using BF-200 ALA versus placebo and the BF-RhodoLED(R) lamp. J Eur Acad Dermatol Venereol. 2025 Aug;39(8):1449-1459. doi: 10.1111/jdv.20452. Epub 2024 Dec 12.

  PMID: 39666443 DERIVED

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

Aminolevulinic Acid; Photochemotherapy; 1-phenyl-3,3-dimethyltriazene

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Levulinic Acids; Keto Acids; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Combined Modality Therapy; Therapeutics; Drug Therapy; Phototherapy

Results Point of Contact

• Title: Clinical Trial Department,
• Organization: Biofrontera Bioscience GmbH

ameluz@biofrontera.com

+49 2148763226

Study Officials

• Uwe Reinhold, Prof. Dr.

  Dermatologisches Zentrum Bonn

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2013
• First Posted: October 21, 2013
• Study Start: October 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: April 1, 2015
• Last Updated: July 28, 2023
• Results First Posted: December 19, 2016

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)