Daylight-PDT for AKs: Comparing Two Photosensitizers (BF-200 ALA and MAL)

NCT ID: NCT01893203

Last Updated: 2016-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2014-12-31

Brief Summary

The aim of the study is to compare the efficacy of two photosensitizers, methyl-aminolaevulinate (MAL) and 5-aminolaevulinic nanoemulsion (BF-200 ALA) in the treatment of facial actinic keratosis. We use randomized, double-blinded prospective study design. The efficacy will be assessed clinically, histopathologically and immunohistochemically.

Detailed Description

Actinic keratoses (AKs) are superficial premalignant skin lesions that can progress into an invasive or metastatic squamous cell carcinoma. AKs can be treated with photodynamic therapy (PDT), of which cure rate compares to cryo surgery with an excellent cosmesis. In PDT the AK lesions are first curettaged, then a photosensitizer is applied on the skin and let to absorb for 3 hours. The skin is illuminated using a blue or red light source light source depending on the photosensitizer, which induces activation of protoporphyrin IX (PpIX) and phototoxic reaction destroying the cancer cells.

The approved photosensitizers in Europe are methyl-aminolevulinic acid cream, (MAL, Metvix™, Galderma), a patch containing 5-aminolevulinic acid (5-ALA, Alacare®, Spirig AG) and 5-aminolevulinic acid gel (BF-200 ALA, Ameluz®, Biofrontera AG) to be used with a red LED light (630-635 nm). In North America a 5-aminolevulinic acid stick (5-ALA, Levulan® Kerastick) can also be used with a blue light source (417 nm).

PpIX absorption peaks are within the visual spectrum of light, which allows PpIX daylight activation. During natural daylight PDT (NDL-PDT) protocol, PpIX is continuously activated during its development, whereas in conventional PDT (LED-PDT) using red LED lamps, large amounts of accumulated PpIX are momentarily activated.

Since skin field cancerization refers to presence of different degrees of visible and invisible dysplastic changes, the whole area should be treated to prevent the development of non-melanoma skin cancers (NMSCs). NDL-PDT enables treatment of field cancerization in one sitting whereas LED-PDT may need repeated illuminations to cover the whole area. NDL-PDT results in enhanced cost-efficacy due to reduced staff expenses, since there's no need for sensitizer absorption and illumination.

At the moment two photosensitizers have marketing authorization in Finland, ALA (Ameluz®) and MAL (Metvix™). We are piloting a study comparing the efficacy of these two light sensitizers in NDL-PDT. The efficacy of the treatments will be assessed clinically, histopathologically and immunohistochemically.

Conditions

Multiple Actinic Keratoses

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

BF-200 ALA vs MAL

BF-200 ALA cream and MAL (Metvix, Galderma) used in a randomized split-face design

Group Type: OTHER

BF-200 ALA cream

Intervention Type: DRUG

The symmetrical treatment areas will be randomized for treatments. First the treatment area will be wiped ethanol. Then sun protection factor (SPF) 20 cream will be applied on all sun-exposed areas of the skin. Then a 0,25mm layer application of Ameluz cream on the area. After appropriate absorption time of 30 minutes, the patients will be taken to the hospital balcony for 2 hour illumination with daylight to accomplish the phototoxic reaction. Maximum dosage will be 2 grams. The treatment will be repeated after 2 weeks for thicker gr II-III lesions with the same protocol.

MAL cream

Intervention Type: DRUG

The symmetrical treatment areas will be randomized for treatments. First the treatment area will be wiped ethanol. Then SPF20 sun protection cream will be applied on all sun-exposed areas of the skin. Then a 0,25mm layer application of Metvix cream on the area. After appropriate absorption time of 30 minutes, the patientswill be taken to the hospital balcony for 2 hour illumination with daylight to accomplish the phototoxic reaction. Maximum dosage will be 2 grams. The treatment will be repeated after 2 weeks for thicker gr II-III lesions with the same protocol.

Interventions

BF-200 ALA cream

The symmetrical treatment areas will be randomized for treatments. First the treatment area will be wiped ethanol. Then sun protection factor (SPF) 20 cream will be applied on all sun-exposed areas of the skin. Then a 0,25mm layer application of Ameluz cream on the area. After appropriate absorption time of 30 minutes, the patients will be taken to the hospital balcony for 2 hour illumination with daylight to accomplish the phototoxic reaction. Maximum dosage will be 2 grams. The treatment will be repeated after 2 weeks for thicker gr II-III lesions with the same protocol.

Intervention Type: DRUG

MAL cream

The symmetrical treatment areas will be randomized for treatments. First the treatment area will be wiped ethanol. Then SPF20 sun protection cream will be applied on all sun-exposed areas of the skin. Then a 0,25mm layer application of Metvix cream on the area. After appropriate absorption time of 30 minutes, the patientswill be taken to the hospital balcony for 2 hour illumination with daylight to accomplish the phototoxic reaction. Maximum dosage will be 2 grams. The treatment will be repeated after 2 weeks for thicker gr II-III lesions with the same protocol.

Intervention Type: DRUG

Other Intervention Names

5-aminolaevulenic acid nanoemulsion; Ameluz; methylaminolevulinic acid; Metvix

Eligibility Criteria

Inclusion Criteria

• actinic keratoses symmetrically on face or scalp
• age over 18 years
• there must be at minumum one ak sized 6mm2 symmetrically on both sides
• patients must be able to make the decision to attend independently

Exclusion Criteria

• pregnancy
• lactation
• lack of compliance

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Joint Authority for Päijät-Häme Social and Health Care

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Noora E Neittaanmäki-Perttu, MD

Role: PRINCIPAL_INVESTIGATOR

Helsinki University Central Hospital

Toni T Karppinen, MD

Role: PRINCIPAL_INVESTIGATOR

Päijät Häme Central Hospital

Taneli Tani, PhD

Role: STUDY_CHAIR

Päijät Häme Central Hospital

Locations

Päijät-Häme Central Hospital

Lahti, , Finland

Countries

Finland

Study Documents

Document Type: Clinical Study Report

View Document

Other Identifiers

2013-002108-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

R13073 / Q257

Identifier Type: -

Identifier Source: org_study_id