A Multicenter Study to Evaluate the Safety and Efficacy of PEP005 Topical Gel When Used to Treat Actinic Keratoses on the Head (Face or Scalp)

Study Overview
=================
Brief Summary
-----------------
This Phase IIb study is designed to assess the safety and efficacy of 0.005%, 0.01% and 0.015% PEP005 Topical Gel when applied to an area of skin, containing 4-8 AK lesions on the face or scalp.

Official Title
-----------------
A Multicenter, Randomized, Double-blind, Vehicle-controlled, Dose-ranging Study to Evaluate the Safety and Efficacy of 0.005%, 0.01% and 0.015% PEP005 Topical Gel When Used to Treat Actinic Keratoses on the Head (Face or Scalp)

Conditions
-----------------
Actinic Keratosis

Intervention / Treatment
-----------------
* Drug: PEP005 Topical Gel
* Drug: PEP005 Topical Gel
* Drug: PEP005 Topical Gel
* Drug: Vehicle gel
* Drug: PEP005 Topical Gel
* Drug: PEP005 Topical Gel
* Drug: PEP005 Topical Gel
* Drug: Vehicle gel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must be male or female Female patients must be of Non-childbearing potential; Childbearing potential, provided negative pregnancy test and using effective contraception 4 to 8 AK lesions on the face or scalp Exclusion Criteria: Cosmetic or therapeutic procedures within 2 weeks and within 2 cm of the selected treatment area. Treatment with immunomodulators, or interferon/ interferon inducers or systemic medications that suppress the immune system: within 4 weeks. Treatment with 5-FU, imiquimod, diclofenac, or photodynamic therapy: within 8 weeks and 2 cm of treatment area

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: PEP005 Topical Gel<br>* 0.005%, two days treatment<br>|
| Experimental: 2<br> | Drug: PEP005 Topical Gel<br>* 0.01%, two days treatment<br>|
| Experimental: 3<br> | Drug: PEP005 Topical Gel<br>* 0.015%, two days treatment<br>|
| Placebo Comparator: 4<br> | Drug: Vehicle gel<br>* two days treatment<br>|
| Experimental: 5<br> | Drug: PEP005 Topical Gel<br>* 0.005%, three days treatment<br>|
| Experimental: 6<br> | Drug: PEP005 Topical Gel<br>* 0.01%, three days treatment<br>|
| Experimental: 7<br> | Drug: PEP005 Topical Gel<br>* 0.015%, three days treatment<br>|
| Placebo Comparator: 8<br> | Drug: Vehicle gel<br>* three days treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AEs Recorded Throughout the Study | Incidence of AEs recorded throughout the study | 57 days | 
| Incidence of SAE Recorded Throughout the Study | Incidence of SAE recorded throughout the study | 57 days | 
| Incidence Rate and Severity of LSRs Following Study Medication Application | The treatment area was assessed at baseline, Day 1 (pre-dose), and at each subsequent study visit for the presence and grade (0 to 4) of the following LSRs: erythema; flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. A composite LSR score (0 to 24), reflecting the sum of each individual LSR grade, was calculated for each patient at each visit. The actual value and change from baseline in the composite LSR score were also summarized. | Baseline | 
| Incidence Rate and Severity of LSRs Following Study Medication Application | The treatment area was assessed at baseline, Day 1 (pre-dose), and at each subsequent study visit for the presence and grade (0 to 4) of the following LSRs: erythema; flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. A composite LSR score (0 to 24), reflecting the sum of each individual LSR grade, was calculated for each patient at each visit. The actual value and change from baseline in the composite LSR score were also summarized. | Day 57 | 
| Incidence of Hyperpigmentation Following Study Medication Application | The selected treatment area was assessed for hyperpigmentation at baseline (Day 1 pre-dose), Day 57, and at each poststudy followup visit as warranted. | Baseline | 
| Incidence of Hyperpigmentation Following Study Medication Application | The selected treatment area was assessed for hyperpigmentation at baseline (Day 1 pre-dose), Day 57, and at each poststudy followup visit as warranted. If any pigmentation was present, the significance and extent of pigmentation and scarring was recorded. At all timepoints, pigmentation evaluations were performed by a board certified Dermatologist (or equivalent) | Day 57 | 
| Incidence of Hypopigmentation Following Study Medication Application | The selected treatment area was assessed for hypopigmentation at baseline (Day 1 pre-dose), Day 57, and at each poststudy followup visit as warranted. If any pigmentation was present, the significance and extent of pigmentation and scarring was recorded. At all timepoints, pigmentation evaluations were performed by a board certified Dermatologist (or equivalent) | Baseline | 
| Incidence of Hypopigmentation Following Study Medication Application | The selected treatment area was assessed for hypopigmentation at baseline (Day 1 pre-dose), Day 57, and at each poststudy followup visit as warranted. If any pigmentation was present, the significance and extent of pigmentation and scarring was recorded. At all timepoints, pigmentation evaluations were performed by a board certified Dermatologist (or equivalent) | Day 57 | 
| Incidence of Scarring Following Study Medication Application | The selected treatment area was assessed for scarring at baseline (Day 1 pre-dose), Day 57, and at each poststudy followup visit as warranted. If any scarring was present, the significance and extent of scarring was recorded. At all timepoints, pigmentation evaluations were performed by a board certified Dermatologist (or equivalent) | Baseline | 
| Incidence of Scarring Following Study Medication Application | The selected treatment area was assessed for scarring at baseline (Day 1 pre-dose), Day 57, and at each poststudy followup visit as warranted. If any scarring was present, the significance and extent of scarring was recorded. At all timepoints, pigmentation evaluations were performed by a board certified Dermatologist (or equivalent). | Day 57 | 
| Complete Clearance Rate of AK Lesions; | Defined as the number of patients at the day 57 post-treatment visit with no clinically visible AK lesions in the selected treatment area | Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy (Clearance of AK Lesions) Partial Clearance Rate | Partial clearence rate, defined as the number of patients at the Day 57 visit with a 75% or greater reduction in the number of AK lesions identified at baseline, in the Face and Scalp | 57 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Peplin, Actinic keratosis, PEP005