Daylight Photodynamic Therapy for Actinic Keratosis

Actinic keratoses (AK) are common precancerous skin lesions that arise on sun-damaged skin.
Treatment is aimed at preventing progression to cutaneous squamous cell carcinoma (SCC).
First-line therapy for clinically apparent lesions includes cryotherapy and curettage; and
field therapy options are topical 5-fluorouracil, imiquimod, ingenol mebutate, and
photodynamic therapy (PDT). PDT involves the topical application of aminolevulinic acid
(ALA), or one of its derivatives, as a photosensitizing agent. In response, rapidly
proliferating, dysplastic cells preferentially accumulate protoporphyrin IX (PpIX). When PpIX
is activated by blue or red light, singlet oxygen species are produced, resulting in cell
death. PDT is beneficial due to its brief treatment course and efficacy in clearing AK.
However, its main drawbacks are the adverse effects of pain, burning, pruritus, erythema,
crusting, and inflammation associated with treatment. While conventional PDT uses red or blue
artificial light to activate a high concentration of accumulated protoporphyrins, daylight
PDT uses natural daylight to activate lower levels of protoporphyrins in a continuous manner.
Daylight PDT, when compared with conventional PDT, has been associated with significantly
less pain while achieving comparable efficacy for the treatment of AK. Daylight PDT is also
more cost-effective and reduces the amount of time spent in clinic. Previous randomized
studies comparing daylight PDT with conventional PDT have largely used methyl-aminolevulinate
as the photosensitizer, have been intra-individual comparative studies, and have been
performed in Nordic countries. Because the effective light dose from natural daylight depends
on geographic location and seasonal and weather changes, randomized trials in different
geographic and environmental conditions are of interest. The proposed randomized clinical
trial investigates the tolerability and efficacy of daylight ALA-PDT for the treatment of AK
in San Francisco for the first time; subjects will be randomized to various treatment arms,
as opposed to previous split-face and intra-individual studies.

Inclusion Criteria:

- Adults at least 18 years old.

- Subjects must be able to read, sign, and understand the informed consent

- Subjects have at least 4 and no more than 20 clinically typical, visible actinic
keratoses in the target treatment area on the face or scalp.

- Subject must be willing to forego any other treatments for AK in the treatment area on
the face or scalp, during the study period, and for 14 days prior to screening;
including cryotherapy, topical 5-fluorouracil, imiquimod, and ingenol mebutate.

- Subjects who have previously received PDT must undergo at least an 8-week washout
period prior to enrollment in study.

- Subject must be willing and able to participate in the study and to comply with all
study requirements including concomitant medication and other treatment restrictions,
and telephone interview.

- If subject is a female of childbearing potential she must have a negative urine
pregnancy test result prior to study treatment initiation and must agree to use an
approved method of birth control while enrolled in the study. Women who are pregnant,
lactating, or planning to become pregnant during the study period are excluded from
the study.

Exclusion Criteria:

- Subjects with any dermatologic disease in the treatment area that may be exacerbated
by the treatment proposed or that might impair the evaluation of AKs.

- Subjects who are currently participating in another clinical study or have completed
another clinical study with an investigational drug or device on the study area within
30 days prior to study treatment initiation.

- Subjects with any medical condition that, in the opinion of the investigator, makes
the patient unsuitable for the trial.