Multiple Actinic KeratosesPhase 42013-002108-15NCT01893203
Daylight-PDT for AKs: Comparing Two Photosensitizers (BF-200 ALA and MAL)
A Phase 4 study testing BF-200 ALA cream and MAL cream in people with Multiple Actinic Keratoses, run by Joint Authority for Päijät-Häme Social and Health Care at 1 site in Finland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Actinic Keratoses
- What is being tested?
- BF-200 ALA cream and MAL cream
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteFinland
- Study dates
- Aug 2013to Dec 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- pregnancy
- lactation
- lack of compliance
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of AKs With Daylight-PDT: Comparing Two Photosensitizers (BF-200 ALA and MAL)
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.
Read the 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
- Being tested
- BF-200 ALA cream, MAL cream
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BF-200 ALA creamDrug
Also called 5-aminolaevulenic acid nanoemulsion, Ameluz
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 creamDrug
Also called methylaminolevulinic acid, Metvix
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.
| Study group | Role | What they receive |
|---|---|---|
| BF-200 ALA vs MAL | Other | BF-200 ALA cream and MAL (Metvix, Galderma) used in a randomized split-face design Receives: Drug: BF-200 ALA cream; Drug: MAL cream |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 0 (baseline) and 3 months
Secondary outcomes (2)
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.
Measured: 12 hours
Clinical Lesion Clearance
Clinical lesion clearance is observed by a blinded observer
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2013 (estimated)
- Study startAug 2013
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple Actinic KeratosesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joint Authority for Päijät-Häme Social and Health Care
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Noora E Neittaanmäki-Perttu, MD, Principal investigator, Helsinki University Central HospitalToni T Karppinen, MD, Principal investigator, Päijät Häme Central HospitalTaneli Tani, PhD, Study chair, Päijät Häme Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01893203
- Sponsor's protocol ID
- R13073 / Q257
- Other IDs
- 2013-002108-15
- Acronym
- 2013-002108-15
- Status last verified
- May 2016
- First submitted
- 2 Jul 2013
- Last updated
- 11 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of AKs With Daylight-PDT: Comparing Two Photosensitizers (BF-200 ALA and MAL)
- ClinicalTrials.gov ID
- NCT01893203
- Acronym / sponsor ID
- 2013-002108-15 / R13073 / Q257
- Conditions
- Multiple Actinic Keratoses
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Joint Authority for Päijät-Häme Social and Health CareUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 8 Jul 2013 (estimated)
- Results
- Posted 11 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BF-200 ALA vs MAL | Other | Drug: BF-200 ALA cream, Drug: MAL creamBF-200 ALA cream and MAL (Metvix, Galderma) used in a randomized split-face design |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- pregnancy
- lactation
- lack of compliance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BF-200 ALA creamAlso: 5-aminolaevulenic acid nanoemulsion, AmeluzThe 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. | Drug | BF-200 ALA vs MAL |
| MAL creamAlso: methylaminolevulinic acid, MetvixThe 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. | Drug | BF-200 ALA vs MAL |
Primary outcome
Histological Lesion Clearance
Time frame: 0 (baseline) and 3 months
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)
2 secondary outcomes
Pain
Time frame: 12 hours
Clinical Lesion Clearance
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Noora E Neittaanmäki-Perttu, MD principal investigator
Helsinki University Central Hospital
Toni T Karppinen, MD principal investigator
Päijät Häme Central Hospital
Taneli Tani, PhD study chair
Päijät Häme Central Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing BF-200 ALA cream and MAL cream in people with Multiple Actinic Keratoses, run by Joint Authority for Päijät-Häme Social and Health Care at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Histological Lesion Clearance (time frame: 0 (baseline) and 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2016.