Light Dose Ranging Study of Photodynamic Therapy (PDT) With Levulan + Blue Light Versus Vehicle + Blue Light in Severe Facial Acne

A Randomized, Evaluator-blinded, Parallel Group Light Dose Ranging Study of Photodynamic Therapy With Levulan Topical Solution + Blue Light Versus Levulan Topical Solution Vehicle + Blue Light on Moderate to Severe Facial Acne Vulgaris

The purpose of this study is to determine and compare the safety and efficacy of multiple broad area photodynamic therapy treatments with aminolevulinic acid (ALA-PDT) and vehicle (VEH-PDT) in subjects with moderate to severe facial acne vulgaris.

This is a Phase II multicenter, randomized, evaluator-blinded, vehicle-controlled, parallel group light dose ranging study of photodynamic therapy in subjects with moderate to severe facial acne vulgaris.

Subjects will be randomized to one of the following four treatment groups (1:1:1:1) to receive topical Levulan® Kerastick® containing 20% aminolevulinic acid HCL (ALA, active study drug) or the Kerastick® containing vehicle ingredients only (VEH).

• Group 1 will have ALA applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds)
• Group 2 will have ALA applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 500 seconds (8 minutes 20 seconds)
• Group 3 will have VEH applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 1000 seconds (16 minutes 40 seconds)
• Group 4 will have VEH applied to the entire facial area 45 minutes ± 15 minutes prior to BLUE light treatment for 500 seconds (8 minutes 20 seconds)

Each subject may receive up to four treatments at three week (± 2 days) intervals. The power density (dose rate) and the total fluence (light dose) used at each treatment is intended to remain constant throughout each subject's participation. If a subject meets or exceeds the criteria restricting retreatment (CRR) prior to retreatment (Section 5.6), he/she will not receive additional PDT treatment at that visit and will be asked to return for the next scheduled PDT visit 3 weeks later, if applicable.

Post-treatment follow-up visits will be scheduled to occur at 3 and 6 weeks after the subject's final PDT.

Grading of the subject's facial acne will be conducted by a blinded evaluator who will remain blinded with respect to the subject's treatment assignment. Tolerability of treatment will be assessed by evaluations of the local skin response (erythema, edema, etc.) and will be conducted by an unblinded evaluator.

Safety will be evaluated by adverse events and local skin responses reported during the study.

Inclusion Criteria:

• Subject is male or non-pregnant female 12 years of age or older.
• Females must be post-menopausal, surgically sterile or using a medically acceptable form of birth control, with a negative urine pregnancy test at the Baseline visit.
• Subject has provided written and verbal informed consent. A subject under 18 years of age must be accompanied by the parent or legal guardian at the time of assent/consent signing. The parent or legal guardian must also provide informed consent for the subject.
• Subject has moderate to severe facial acne vulgaris (including the nose), with at least 20 inflammatory lesions (papules, pustules, nodules).
• Subject has moderate to severe acne as defined by an Investigator Global Assessment of 3 or 4 [0 (clear) to 4 (severe) scale].
• Subject has a history of recurrent herpes simplex labialis infection in the treatment area AND has had an outbreak within the last 12 months must be placed on antiviral prophylaxis as specified in the protocol.
• Subject is willing to comply with study instructions and return to the clinic for required visits.
• Subject must have used the same type and brand of make-up, other facial products and hair products (e.g. shampoo, gel, hair spray, mousse, etc.) for at least 1 month prior to the Baseline Visit (General Skin & Hair Care). Upon enrollment, all subjects must a) use exclusively an Investigator approved facial cleanser and b) agree to continue their other General Skin & Hair Care for the entire study.

Exclusion Criteria:

• Subject is pregnant, lactating, or is planning to become pregnant during the study.
• Subject has a history of cutaneous photosensitization, porphyria, hypersensitivity to porphyrins or photodermatosis.
• Subject has any skin pathology or condition that could interfere with the evaluation of the test product or requires the use of interfering topical or systemic therapy.
• Subject has greater than 4 facial nodules (nodule = lesion greater than or equal 0.5 cm in diameter)
• Subject has an uncorrected coagulation defect or concurrently uses anticoagulants (except aspirin).
• Subject has any condition which, in the investigator's opinion, would make it unsafe for the subject to participate in this research study.
• Subject is currently enrolled in an investigational drug or device study.
• Subject has received an investigational drug or been treated with an investigational device within 30 days prior to the initiation of treatment (baseline).
• Subject has facial hair that could interfere with the study assessments in the opinion of the investigator.
• Subject is unable to communicate or cooperate with the investigator due to language problems, poor mental development, or impaired cerebral function.
• Subject may be unreliable for the study including subjects who engage in excessive alcohol intake or drug abuse, or subjects who are unable to return for scheduled follow-up visits.
• Subject has a known sensitivity to one or more of the vehicle components (ethyl alcohol, isopropyl alcohol, laureth 4, polyethylene glycol).
• Subject has used photosensitizing drugs, e.g. declomycin, tetracycline, sulfa antibiotics, phenothiazines, etc. within a timeframe where photosensitization from these drugs may still be present.
• Subject has used OTC acne medicated cleansers or soaps within 2 weeks of the initiation of treatment.
• Subject has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the trial.
• Subject has used any of the following topical anti-acne preparations on the face: a.) Topical anti-acne treatments including benzoyl peroxide, antibiotics, azelaic acid, corticosteroids and salicylic acid within 2 weeks of the initiation of treatment b.) Retinoids, including tazarotene, adapalene, tretinoin within 4 weeks of the initiation of treatment. c.) Light treatments, microdermabrasion or chemical peels within 8 weeks of the initiation of treatment.
• Subject has used any of the following systemic anti-acne medications: a.) Corticosteroids (including intramuscular and intralesional injections) within 4 weeks of the initiation of treatment. Inhaled corticosteroids are allowed if use is stable (stable use is defined as dose and frequency unchanged for at least 2 weeks prior to the initiation of treatment). b.) Antibiotics within 4 weeks of the initiation of treatment. c.) Nicotinamide containing products within 4 weeks of the initiation of treatment. d.) Spironolactone within 8 weeks of the initiation of treatment. d.) Retinoid therapy within 6 months of the initiation of treatment.