Short Incubation Methylaminolevulinate Photodynamic Therapy Without Occlusion

Phase 3

Completed

Conditions: Actinic Keratosis

Interventions: Drug: Methylaminolevulinate (Metvix, Metvixia)
Device: Photodynamic Therapy (Aktilite)

Registration Number: NCT00926952

Lead Sponsor: Innovaderm Research Inc.

Brief Summary: Actinic keratoses on the face are often numerous and widespread. The application of Methylaminolevulinate (MAL) on individual lesions followed by the application of a plastic film on each lesion is difficult and takes time for subjects with many actinic keratoses. The waiting period of 3 hours between MAL cream application and red light exposure is also long for patients. The goal of this study is to evaluate the safety and efficacy of photodynamic therapy (PDT) with MAL with a shorter cream application time (90 minutes) and when MAL is applied on the entire face without the plastic film.

Detailed Description: A total of 20 patients with at least 5 non-hypertrophic actinic keratoses (AK) of the face were included in this open-label study. All AKs were mapped on a transparent template before the first PDT treatment. At Day 0, all patients received methylaminolevulinate (MAL) applied on the entire face (except the nose and peri-ocular area of 1-2 cm) without any skin preparation. One to two 2 g MAL tubes was used for the entire face. MAL was applied without occlusion. After a total of 90 +/- 5 minutes the skin was rinsed and exposed to 37 J/cm² of red light from an Aktilite™ device. Patients were seen at Week 4; if all facial AKs did not show a complete response to treatment, the MAL-PDT procedure was repeated at Week 4. Patients were seen again at Week 12 and 24.

The primary endpoint was at Week 12. Patients came back at Week 24 for a final safety evaluation and to verify the recurrence of AK.

Efficacy is evaluated by assessing the mean number of facial AK at Week 12 as compared to Day 0.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Age 18 or older.
Patient with at least 5 actinic keratoses of the face at Day 0.
Patient was willing to use an adequate contraceptive method or was surgically sterile, post menopausal, abstinent or with a same sex partner. Adequate means of contraception included oral contraceptives, IUD in use for 30 days before Day 0, barrier methods and spermicide in use at least 14 days before Day 0.
Patient capable of giving informed consent.

Exclusion Criteria

Patient with allergy to methylaminolevulinate or any component of the vehicle which includes peanut and almond oil.
Patient with clinically significant sensitivity to visible light, porphyria or porphyrin sensitivity.
Patient used any topical treatment for actinic keratoses (including imiquimod and 5-fluouracil), on the face within 4 weeks preceding Day 0.
Patient had cryotherapy or surgery on the face within 4 weeks preceding Day 0.
Patient with any malignant skin lesion (such as basal cell carcinoma, invasive squamous cell carcinoma or Bowen's disease) on the face at Day 0.
Patient used photodynamic therapy, with any topical or systemic photosensitizer within 8 weeks preceding Day 0.
Patient was exposed to excessive ultraviolet radiation (UVB phototherapy, sun tanning salons) within the 4 weeks preceding Day 0.
Patient used any investigational drug within 4 weeks preceding Day 0.
Patient with problems of alcoholism or drug abuse in the past year.
Patient with any unstable or serious uncontrolled medical condition.
Current pregnancy or lactation.
Patient with any serious dermatological disorder, including malignancies that would either put the patient at risk or interfere with efficacy or safety evaluations.
Patient with Fitzpatrick phototype IV, V or VI (inadequate penetration of red light in dark skinned subjects.
Patients with extensive facial hair (e.g., beard) that would either impair red light exposure or interfere with lesion evaluation.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MAL-PDT 90 min incubation, no occlusion	Methylaminolevulinate (Metvix, Metvixia)	Patients had 2-4 g of Methylaminolevulinate (MAL) spread on the entire face without occlusion and waited 90 minutes prior to photodynamic therapy (PDT) using red light.
MAL-PDT 90 min incubation, no occlusion	Photodynamic Therapy (Aktilite)	Patients had 2-4 g of Methylaminolevulinate (MAL) spread on the entire face without occlusion and waited 90 minutes prior to photodynamic therapy (PDT) using red light.

Primary Outcome Measures

Name	Time	Method
Mean Number of Facial Actinic Keratoses at Week 12	12 weeks

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Complete Clinical Response of All Actinic Keratoses at Week 12	12 weeks	The proportion of patients with a complete clinical response is calculated by dividing the number of patients with a complete response at week 12 by the number of participants at baseline.
Number of Actinic Keratosis Lesions With Complete Clinical Response at Day 0 and Week 12	0, 12 weeks
Mean Griffiths Photonumeric Scale for Photodamage Score at Week 12	12 weeks	Griffiths photonumeric scale was evaluated by the dermatologist. Patients were placed under natural daylight or fluorescent lighting for grading. A direct comparison was then made between the subjects and photographic standards (provided in reference 1). If an exact match could not be made to a grade then an inter-grade number was used used, for example 1, 3, 5, or 7. Zero (0) is the least amount of photodamage, 8 is the most amount of photodamage.
Mean Fine Wrinkling Score at Week 12	12 weeks	This factor represents a visual assessment of the number and depth of superficial wrinkles (i.e. shallow indentations or lines). Fine wrinkles typically appear in periorbital and perioral regions and are usually found further from the eyes and mouth than are coarse wrinkles. Rating Category 0 None 1-3 Mild 4-6 Moderate 7-9 Severe
Mean Coarse Wrinkling Score at Week 12	12 weeks	This factor represents a visual assessment of the number and depth of coarse wrinkles (i.e. deep lines, furrows, or creases). Coarse wrinkles appear on the forehead, glabella, chin, and nasolabial and periorbital areas, and they tend to be located closer to the eyes and mouth than fine wrinkles. Rating Category 0 None 1-3 Mild 4-6 Moderate 7-9 Severe
Mean Sallowness Score at Week 12	12 weeks	This factor represents a visual assessment of color tone from very pink or rosy (0) to very sallow or pale (9). Rating Category 0 None 1-3 Mild 4-6 Moderate 7-9 Severe
Mean Mottled Hyperpigmentation at Week 12	12 weeks	This factor represents a visual assessment of light, patchy, mottled hyperpigmentation and solar freckling (including melasma) based on quantitative criteria such as the area/density of pigment, color intensity (dark vs. light), and uniformity of distribution (i.e. the more uneven or blotchy, the greater the score), Lentigines, nevi, and other pigmented lesions are not to be included in this assessment. Rating Category 0 None 1-3 Mild 4-6 Moderate 7-9 Severe
Number of Adverse Events	12, 24 weeks	To study the safety of MAL-PDT performed without occlusion when red light exposure takes place 90 minutes after the application of MAL by tracking adverse events until week 12 and adverse events until week 24