Actinic Keratosis
Conditions
Keywords
Methyl aminolevulinate, Photodynamic therapy, Aktilite CL128 LED light source, Multiple Actinic Keratosis
Brief summary
The purpose of this study was to compare the efficacy of Photodynamic Therapy (PDT) with methyl aminolevulinate (MAL) cream to PDT with vehicle cream, using the Light-emitting diode (LED) light source Aktilite CL128, in treatment of participants with multiple actinic keratosis (sun-damaged skin) on the face and/or scalp.
Detailed description
Actinic keratoses are pre-malignant skin lesions, which may develop to squamous cell carcinomas (SCC). They are usually small, thin, erythematous, de-squamating lesions on light exposed atrophic skin and the lesions are often multiple. Photodynamic therapy (PDT) is the selective destruction of abnormal cells through light activation of a photosensitiser in the presence of oxygen. These cells accumulate more photosensitiser than normal cells. The photosensitiser generates reactive oxygen species upon illumination. For skin diseases, such as actinic keratosis (AK), there has been an increasing interest in using topically applied precursors of the photoactive porphyrins (PAP). The most commonly used precursors have been 5-aminolevulinic acid (ALA) and its derivatives. The present test drug contains methyl aminolevulinate, which penetrates the lesions well and shows high lesion selectivity. Different light sources (i.e. CureLight, Aktilite CL16 and Aktilite CL128) had been used for the activation of PAP, which absorbs light in the range of 400-700 nanometer (nm). The present study used the Aktilite CL 128 lamp. Aktilite 128 was based on LED technology and emits a narrow red light spectrum with an average wavelength of 630 (+/-5) nm. This study was similar to two other studies performed, on which the U.S. approval of Metvixia cream was based except for the light source used. This study was one of two studies performed to document the safety and efficacy of the Aktilite CL 128 lamp when used in combination with Metvixia cream. Previous studies have shown that the risks attributed to Metvixia PDT are few and related mainly to transient pain and local erythema during and shortly after treatment. These reactions are part of the expected local phototoxicity reaction. PDT offers an advantage to other treatment modalities for actinic keratosis, being a non-invasive treatment available on an outpatient basis. Several separate lesions can be treated simultaneously and the same lesion(s) can be treated repeatedly with success. There are no known systemic toxicity or interaction with other medication. The treatment is also lesion selective, leaving the surrounding tissue intact and functional, also allowing excellent cosmetic results after treatment.
Interventions
COMBINATION_PRODUCTMetvix-PDT
Metvix 160 mg/g Cream was applied for 3 hours with occlusive dressing, and illumination with non-coherent red light using the Aktilite CL128 lamp, with a total light dose 37 Joule/square centimeter (J/cm²). All eligible lesions on the participant were treated twice with an interval of 1 week between treatments.
COMBINATION_PRODUCTVehicle-PDT
Vehicle Cream was applied for 3 hours with occlusive dressing, and illumination with non-coherent red light using the Aktilite CL128 lamp, with a total light dose 37 J/cm². All eligible lesions on the participant were treated twice with an interval of 1 week between treatments.
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of 4-10 previously untreated, not pigmented, non-hyperkeratotic AK lesions of 3 mm or more diameter of Grade 1 and/or 2 of the face and/or scalp where other therapies are unacceptable or considered medically less appropriate. * Males or females above 18 years of age. * Written informed consent.
Exclusion criteria
* Participants with porphyria. * Participants immunosuppressed for idiopathic, disease specific or therapeutic reasons. * Known allergy to MAL, a similar PDT compound or excipients of the cream. * Participants with history of hypersensitivity to nut products or other known protein antigens. * Participation in other clinical studies either currently or within the last 30 days. * Participants receiving local treatment (including cryotherapy and curretage) in face / scalp area within the last 30 days. * Participants receiving topical treatment (including imiquimod, 5-FU and diclofenac) in face / scalp area within the last 3 months. * Pregnant or breast-feeding: All women of child-bearing potential must use adequate contraception (oral contraceptives, intrauterine device, contraceptive skin patch, etc) during the treatment period and one month thereafter. In addition, they must have a negative pregnancy test prior to treatment. * Any conditions that may be associated with a risk of poor protocol compliance. * Participants currently receiving regular ultraviolet radiation therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant Complete Response Rate (CRR) | At Week 13 | Participant complete response rate was defined as the percentage of participants with complete response. Complete response was defined as the complete disappearance of the lesion determined by clinical assessment (visual inspection and palpation) by an investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lesion Complete Response Rate | At Week 13 | Lesion complete response rate was defined as the percentage of pre-existing and treated lesions at baseline that were assessed as clear (complete disappearance of the lesion, visually and by palpation) after treatment. Percentage of lesions reported by location. |
| Number of Participants With at Least One Treatment Site Adverse Events | From start of study drug administration up to Week 13 | An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily had a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Number of participants with at least one treatment site adverse events were reported. |
Countries
Germany, United States
Participant flow
Recruitment details
The study was conducted at 12 centers in Germany and the United States from 13 March 2006 to 23 January 2007.
Pre-assignment details
A total of 131 participants were enrolled and received treatment in this study.
Participants by arm
| Arm | Count |
|---|---|
| Metvix-PDT Participants received Metvix-PDT 160 mg/g cream on face and/or scalp for 3 hours on Day 0 and Day 7. | 73 |
| Vehicle-PDT Participants received Vehicle-PDT on face and/or scalp for 3 hours on Day 0 and Day 7. | 58 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Protocol Deviations/Violations | 15 | 0 |
Baseline characteristics
| Characteristic | Metvix-PDT | Vehicle-PDT | Total |
|---|---|---|---|
| Age, Continuous | 70.0 years STANDARD_DEVIATION 8.4 | 67.0 years STANDARD_DEVIATION 10.4 | 68.7 years STANDARD_DEVIATION 9.4 |
| Race/Ethnicity, Customized Caucasian | 73 Participants | 58 Participants | 131 Participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Male | 60 Participants | 45 Participants | 105 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 73 | 0 / 58 |
| other Total, other adverse events | 62 / 73 | 34 / 58 |
| serious Total, serious adverse events | 6 / 73 | 3 / 58 |
Outcome results
Primary
Participant Complete Response Rate (CRR)
Participant complete response rate was defined as the percentage of participants with complete response. Complete response was defined as the complete disappearance of the lesion determined by clinical assessment (visual inspection and palpation) by an investigator.
Time frame: At Week 13
Population: Intention-to-treat (ITT) population consisted of all participants that were randomized and for whom any aspect of treatment with either Metvix-PDT or Vehicle-PDT was initiated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metvix-PDT | Participant Complete Response Rate (CRR) | 68.4 Percentage of participants |
| Vehicle-PDT | Participant Complete Response Rate (CRR) | 6.9 Percentage of participants |
Secondary
Lesion Complete Response Rate
Lesion complete response rate was defined as the percentage of pre-existing and treated lesions at baseline that were assessed as clear (complete disappearance of the lesion, visually and by palpation) after treatment. Percentage of lesions reported by location.
Time frame: At Week 13
Population: Intention-to-treat (ITT) population consisted of all participants that were randomized and for whom any aspect of treatment with either Metvix-PDT or Vehicle-PDT was initiated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metvix-PDT | Lesion Complete Response Rate | Face | 89 Percentage of lesions |
| Metvix-PDT | Lesion Complete Response Rate | Scalp | 81 Percentage of lesions |
| Vehicle-PDT | Lesion Complete Response Rate | Face | 28 Percentage of lesions |
| Vehicle-PDT | Lesion Complete Response Rate | Scalp | 30 Percentage of lesions |
Secondary
Number of Participants With at Least One Treatment Site Adverse Events
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily had a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Number of participants with at least one treatment site adverse events were reported.
Time frame: From start of study drug administration up to Week 13
Population: The safety population consisted of all participants for whom any kind of treatment was initiated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metvix-PDT | Number of Participants With at Least One Treatment Site Adverse Events | 61 Participants |
| Vehicle-PDT | Number of Participants With at Least One Treatment Site Adverse Events | 27 Participants |