A Sequential Treatment Regimen of Cryotherapy and Picato® for the Treatment of Actinic Keratosis on the Face and Scalp

Inclusion Criteria:

- Subjects must be competent to understand the nature of the trial and provide informed
consent.

- Subjects with 4 to 8 clinically typical, visible and discrete AKs within a contiguous
25 cm2 treatment area on the face or scalp.

- Subject at least 18 years of age.

- Female subjects must be of either:

- Non-childbearing potential, i.e. post-menopausal or have a confirmed clinical
history of sterility (e.g. the subject is without a uterus) or,

- Childbearing potential, provided there is a confirmed negative urine pregnancy
test prior to study treatment, to rule out pregnancy.

- Female subjects of childbearing potential must be willing to use effective
contraception.

Exclusion Criteria:

- Location of the selected treatment area:

- on any location other than the face or scalp

- within 5 cm of an incompletely healed wound

- within 10 cm of a suspected basal cell carcinoma (BCC) or SCC

- Prior treatment with PEP005 Gel on face or scalp.

- Selected treatment area lesions that have:

- atypical clinical appearance and/or

- recalcitrant disease

- History or evidence of skin conditions other than the trial indication that would
interfere with evaluation of the trial medication

- Clinical diagnosis/history or evidence of any medical condition that would expose a
subject to an undue risk of a significant AE or interfere with assessments of safety
and efficacy.

- Any abnormal vital signs measurements that are medically significant or would impact
the safety of the subject or the interpretation of the trial results.

- Anticipated need for hospitalization or out-patient surgery during the first 15 days
after the first trial medication application.

- Known sensitivity or allergy to any of the ingredients in PEP005 Gel

- Recent excessive exposure to ultraviolet light

- Current enrolment or participation in a clinical trial within 30 days of entry into
this study

- Subjects previously randomised in the trial

- Female subjects who are breastfeeding

Prohibited Therapies and/or Medications within 2 weeks prior to Visit 1

- Cosmetic or therapeutic procedures within 2 cm of the selected treatment area

- Use of acid-containing therapeutic products within 2 cm of the selected treatment
area

- Use of topical medicated creams, ointments, lotions, gels, foams or sprays

Prohibited Therapies and/or Medications: within 4 weeks prior to visit 1:

- Treatment with immunomodulators, cytotoxic drugs or inter-feron /interferon inducers

- Treatment with systemic medications that suppress the immune system

- Treatment/therapy with ultraviolet light A (UVA) or ultraviolet light B (UVB).

Prohibited Therapies and/or Medications within 8 weeks prior to visit 1:

- Treatment with 5-FU, imiquimod, diclofenac sodium, or photodynamic therapy: within 2
cm of the selected treatment area.

Prohibited Therapies and/or Medications within 6 months prior to visit 1

- Use of systemic retinoids or biologic / mono-clonal antibody therapies