Daylight-PDT for AKs: Comparing Two Photosensitizers (BF-200 ALA and MAL) (2013-002108-15)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Joint Authority for Päijät-Häme Social and Health Care
ClinicalTrials.gov Identifier:
NCT01893203
First received: July 2, 2013
Last updated: May 29, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Multiple Actinic Keratoses
Drug: BF-200 ALA cream
Drug: MAL cream
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of AKs With Daylight-PDT: Comparing Two Photosensitizers (BF-200 ALA and MAL)

Resource links provided by NLM:


Further study details as provided by Joint Authority for Päijät-Häme Social and Health Care:

Primary Outcome Measures:
  • Histological Lesion Clearance [ Time Frame: 0 (baseline) and 3 months ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Pain [ Time Frame: 12 hours ] [ Designated as safety issue: Yes ]

    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.


  • Clinical Lesion Clearance [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Clinical lesion clearance is observed by a blinded observer


Other Outcome Measures:
  • Adverse Reactions [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 14
Study Start Date: August 2013
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
BF-200 ALA vs MAL
BF-200 ALA cream and MAL (Metvix, Galderma) used in a randomized split-face design
Drug: 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.
Other Names:
  • 5-aminolaevulenic acid nanoemulsion
  • Ameluz
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.
Other Names:
  • methylaminolevulinic acid
  • Metvix

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01893203

Locations
Finland
Päijät-Häme Central Hospital
Lahti, Finland, 15850
Sponsors and Collaborators
Joint Authority for Päijät-Häme Social and Health Care
Investigators
Principal Investigator: Noora E Neittaanmäki-Perttu, MD Helsinki University Central Hospital
Principal Investigator: Toni T Karppinen, MD Päijänne Tavastia Central Hospital
Study Chair: Taneli Tani, PhD Päijänne Tavastia Central Hospital
  More Information

Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 25109244

Responsible Party: Joint Authority for Päijät-Häme Social and Health Care
ClinicalTrials.gov Identifier: NCT01893203     History of Changes
Other Study ID Numbers: R13073 / Q257  2013-002108-15 
Study First Received: July 2, 2013
Results First Received: December 23, 2015
Last Updated: May 29, 2016
Health Authority: Finland: Finnish Medicines Agency

Additional relevant MeSH terms:
Keratosis
Keratosis, Actinic
Skin Diseases
Precancerous Conditions
Neoplasms
Photosensitizing Agents
Methyl 5-aminolevulinate
Aminolevulinic Acid
Dermatologic Agents

ClinicalTrials.gov processed this record on July 26, 2016