Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2013-002108-15 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BF-200 ALA vs MAL | Other | BF-200 ALA cream and MAL (Metvix, Galderma) used in a randomized split-face design |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BF-200 ALA cream | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Histological Lesion Clearance | Punch biopsies were taken symmetrically on both treatment fields from equally graded >6 mm AKs prior to treatment and again at 3 months, blinded observer (pathologist). HE- and p53-stainings. Samples not fulfilling the criteria of an AK were defined as healthy or completely cleared. The p53 reactivity expressed as average percentage of positive nuclei in three consecutive high power fields from the region of highest reactivity (<10 % normal) | 0 (baseline) and 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Pain | Pain using visual analog scale (VAS 0-10, where 0 is no pain and 10 is the worst pain imaginable) on both treatment sides is assessed in every 30 minutes during 2-hour sun-exposure and afterwards once in two hours until 9 p.m. (treatment day). Of these values, the mean maximal pain is assessed. | 12 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Reactions | Adverse reactions are evaluated by blinded observer at one week after treatment. A dermatologist will assess which side of the face or scalp presents a stronger reaction. | 1 week |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Noora E Neittaanmäki-Perttu, MD | Helsinki University Central Hospital | Principal Investigator |
| Toni T Karppinen, MD | Päijät Häme Central Hospital | Principal Investigator |
| Taneli Tani, PhD | Päijät Häme Central Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Päijät-Häme Central Hospital | Lahti | 15850 | Finland |
Not provided
Not provided
| ID | Type | URL | Comment |
|---|---|---|---|
| 25109244 | Clinical Study Report | View IPD |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | BF200 ALA vs MAL | 5-aminulevulinic acid nanoemulsion (BF-200 ALA, Ameluz, Biofrontera) and methylaminolevulinic acid (MAL, Metvix, Galderma) in randomized split face design on symmetrical treatment areas. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
14 patients were recruited. One withdrew because of conditions not related to the study. This patient was not included in the analysis.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | BF-200 ALA vs MAL | BF-200 ALA cream and MAL (Metvix, Galderma) used in a randomized split-face design |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Histological Lesion Clearance | Punch biopsies were taken symmetrically on both treatment fields from equally graded >6 mm AKs prior to treatment and again at 3 months, blinded observer (pathologist). HE- and p53-stainings. Samples not fulfilling the criteria of an AK were defined as healthy or completely cleared. The p53 reactivity expressed as average percentage of positive nuclei in three consecutive high power fields from the region of highest reactivity (<10 % normal) | Punch biopsies bilaterally on treatment fields | Posted | Number | percentage of complete clearance | 0 (baseline) and 3 months |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BF200 ALA vs MAL | BF-200 ALA (Ameluz, Biofrontera) and MAL (Metvix, Galderma) in randomized slipt face design on symmetrical treatment areas. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adverse reactions: erythema, crusting, scaling | Skin and subcutaneous tissue disorders | Systematic Assessment | Erythema, crusting and scaling were assessed all together as one score of mild, moderate or severe |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Noora Neittaanmäki-Perttu | Helsinki university hospital | +358407190362 | noora.neittaanmaki@fimnet.fi |
Not provided
| ID | Term |
|---|---|
| D000622 | Aminolevulinic Acid |
| C475457 | methyl 5-aminolevulinate |
| ID | Term |
|---|---|
| D007982 | Levulinic Acids |
| D007651 | Keto Acids |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| MAL cream | 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. |
|
|
| Clinical Lesion Clearance |
Clinical lesion clearance is observed by a blinded observer |
| 3 months |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Number of AKs | Number | Number of actinic keratoses (AKs) |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Secondary | Pain | Pain using visual analog scale (VAS 0-10, where 0 is no pain and 10 is the worst pain imaginable) on both treatment sides is assessed in every 30 minutes during 2-hour sun-exposure and afterwards once in two hours until 9 p.m. (treatment day). Of these values, the mean maximal pain is assessed. | Patients | Posted | Mean | Full Range | units on a scale | 12 hours |
|
|
|
| Secondary | Clinical Lesion Clearance | Clinical lesion clearance is observed by a blinded observer | Posted | Number | 95% Confidence Interval | percentage of complete clearance | 3 months | AKs total | Participants |
|
|
|
| Other Pre-specified | Adverse Reactions | Adverse reactions are evaluated by blinded observer at one week after treatment. A dermatologist will assess which side of the face or scalp presents a stronger reaction. | One week after the first photodynamic therapy (PDT), seven patients had more severe reactions (erythema, crusting) at the site treated with BF-200 ALA, five patients had more severe reactions at the MAL site and one patient showed no difference between sites. | Posted | Number | participants | 1 week |
|
|
|
| 0 |
| 13 |
| 13 |
| 13 |
|
| Pain | Skin and subcutaneous tissue disorders | Systematic Assessment | Pain in VAS scale 1-10 |
|
Not provided
Not provided
| D000596 |
| Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| Title | Measurements |
|---|---|
|