Orphan Drug Designation for this indication not granted

The purpose of this study is to determine and compare the safety and efficacy of broad area photodynamic therapy with aminolevulinic acid (ALA-PDT) versus vehicle PDT (VEH-PDT) in the treatment of actinic keratoses (AK) and reduction of new non-melanoma skin cancer (NMSC) of the scalp or both forearms in solid organ transplant recipient subjects receiving chronic immunosuppressive therapy.

This is a Phase II multicenter, randomized, evaluator-blinded, vehicle-controlled, parallel group study of photodynamic therapy in organ transplant recipient subjects for treatment of AK and the reduction of new NMSC.

Subjects will be randomized to one of the following two treatment groups (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 scalp OR both forearms 90 +/- 30 minutes prior to BLUE light treatment for 16 minutes 40 seconds
• Group 2 will have VEH applied to the entire scalp OR both forearms 90 +/- 30 minutes prior to BLUE light treatment for 16 minutes 40 seconds

Treatment Area (scalp or both forearms) must have had at least 2 NMSC in the past 12 months, and must include a continuous 25 cm2 Target Area containing a minimum of 3 AKs, to be eligible for treatment

Each subject may receive up to nine treatments. The initial four (4) ALA-PDT/VEH-PDT treatments will be given at 4-5 week intervals, with the remaining five (5) treatments given every 6 +/-1 weeks. Post-treatment follow-up visit will be scheduled to occur 4 weeks after the subject's final PDT.

Inclusion Criteria:

1. Subject is male or non-pregnant female organ transplant (kidney, liver, pancreas, lungs, heart or combinations thereof) recipient outpatient 18 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.
2. Subject has provided written and verbal informed consent.
3. Subject has at least 3 actinic keratosis lesions in a continuous 25 cm2 Target Area within the selected anatomic treatment site (scalp or forearm).
4. Subject has a history of a minimum of 2 NMSC on the treatment area of interest (scalp OR both forearms) in the past 12 months
5. Subject is currently receiving standard active pharmacologic immunosuppression
6. Subject is willing to comply with study instructions and return to the clinic for required visits.
7. Subject has Fitzpatrick skin type I-IV.

Exclusion Criteria:

1. Subject is pregnant, lactating, or is planning to become pregnant during the study.

2. Subject has a history of cutaneous photosensitization, porphyria, hypersensitivity to porphyrins or photodermatosis.

3. Subject has any skin pathology or condition, in the investigator's opinion, that could interfere with the evaluation of the test product or requires the use of interfering topical or systemic therapy.

4. Subject has any condition which, in the investigator's opinion, would make it unsafe for the subject to participate in this research study.

5. Subject is currently enrolled in an investigational drug (including experimental immunosuppressive agents containing new chemical entities) or device study. Novel combinations of and alternative dosing regimens of approved immunosuppressive agents are allowed.

6. Subject has received an investigational drug (including experimental immunosuppressive agents containing new chemical entities) or been treated with an investigational device within 30 days prior to the initiation of treatment (baseline). Novel combinations of and alternative dosing regimens of approved immunosuppressive agents are allowed.

7. Subject is unable to communicate or cooperate with the investigator due to language problems, poor mental development, or impaired cerebral function.

8. 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.

9. Subject has a known sensitivity to one or more of the vehicle components (ethyl alcohol, isopropyl alcohol, laureth 4, polyethylene glycol).

10. Subject has active recurrent herpes simplex labialis infection in the treatment area with an outbreak within the last 12 months and will not be placed on antiviral prophylaxis as specified in the protocol.

11. Subject has used any of the following topical preparations on the selected Treatment Area (scalp OR both forearms):

    • Keratolytics including urea (greater than 5%), alpha hydroxyacids [e.g. glycolic acid, lactic acid, etc. greater than 5%], salicylic acid (greater than 2%) within 2 days of initiation of treatment.
    • 5-FU, cryotherapy, diclofenac, imiquimod or other treatments for AK within 2 weeks of initiation of treatment
    • Retinoids, including tazarotene, adapalene, tretinoin, retinol, within 4 weeks of the initiation of treatment.
    • Microdermabrasion, laser ablative treatments, ALA-PDT or chemical peels within 8 weeks of the initiation of treatment.
    • Two or more ALA PDT treatments in the past 6 months

12. Subject has used systemic retinoid therapy within 6 months of the initiation of treatment.