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

The purpose of this trial is to compare the rate of complete clearance of actinic keratosis (AK) using sequential cryotherapy and field treatment with PEP005 Gel compared to cryotherapy alone.

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis
• Intervention / Treatment: Procedure: Cryotherapy; Drug: Ingenol metabute; Drug: Vehicle

• Study Type: Interventional
• Enrollment (Actual): 367
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Fremont, California, United States, 94538
      • Center for Dermatology Clinical Research
    • Oceanside, California, United States, 92056
      • Dermatology Specialists, Inc.
    • San Diego, California, United States, 92117
      • Skin Surgery Medical Group, Inc.
    • San Diego, California, United States, 92123
      • University Clinical Trials, Inc.
  • Colorado
    • Denver, Colorado, United States, 80210
      • Colorado Medical Research Center, Inc.
    • Englewood, Colorado, United States, 80113
      • About Skin Dermatology and DermSurgery, PC
  • Florida
    • Aventura, Florida, United States, 33180
      • The Center for Clincial and Cosmetic Research
    • Boynton Beach, Florida, United States, 33437
      • Study Protocol, Inc.
    • Jacksonville, Florida, United States, 32204
      • North Florida Dermatology Associates, PA
    • Tampa, Florida, United States, 33612
      • University of South Florida, Carol and Frank Morsani Center for Advanced Healthcare
  • Georgia
    • Newnan, Georgia, United States, 30263
      • MedaPhase
    • Snellville, Georgia, United States, 30078
      • Gwinnett Clinical Research Center, Inc.
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Altman Dermatology Associates
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Laser & Skin Surgery Center of Indiana
    • Plainfield, Indiana, United States, 46168
      • The Indiana Clinical Trials Center, PC
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Great Lakes Research Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Medical Centre - New Center One, Department of Dermatology
    • Warren, Michigan, United States, 48088
      • Grekin Skin Institute
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Minnesota Clinical Study Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Academic Dermatology Associates
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • Rochester, New York, United States, 14623
      • Skin Search of Rochester, Inc.
    • Smithtown, New York, United States, 11787
      • Long Island Skin Cancer and Dermatologic Surgery
  • Oregon
    • Portland, Oregon, United States, 97223
      • Oregon Medical Research Center, Pc
    • Portland, Oregon, United States, 97239-6483
      • Oregon Health & Science University, Dept. of Dermatology
  • Pennsylvania
    • Fort Washington, Pennsylvania, United States, 19034
      • Philadelphia Institute of Dermatology
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Dermatology Research Associates, Inc.
  • Texas
    • Arlington, Texas, United States, 76011
      • Arlington Research Center, Inc.
    • Houston, Texas, United States, 77056
      • Suzanne Bruce and Associates, P.A.
    • San Antonio, Texas, United States, 78229
      • Dermatology Clinical Research Center of San Antonio
    • Webster, Texas, United States, 77598
      • Center for Clinical Studies
  • Utah
    • Salt Lake City, Utah, United States, 84117
      • Dermatology Research Center, Inc.
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • The Education & Research Foundation, Inc.
    • Norfolk, Virginia, United States, 23507
      • Virginia Clinical Research, Inc.
  • Washington
    • Spokane, Washington, United States, 99204
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PEP005 Gel, 0.015%; Cryotherapy followed by PEP005 Gel, 0.015%	Procedure: Cryotherapy; Cryotherapy of all visible AKs (4-8 lesions, "baseline lesions") in the selected treatment area; Drug: Ingenol metabute; Field treatment with vehicle gel once daily for 3 consecutive days.; Other Names: Picato® gel, 0.015%
Placebo Comparator: Vehicle gel; Cryotherapy followed by vehicle gel	Procedure: Cryotherapy; Cryotherapy of all visible AKs (4-8 lesions, "baseline lesions") in the selected treatment area; Drug: Vehicle; Field treatment with vehicle gel once daily for 3 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Clearance of AKs at Week 11	To determine the 11-week rate of complete clearance of AKs (defined as no clinically visible AKs) in the selected treatment area using sequential cryotherapy and field treatment with PEP005 Gel compared to cryotherapy alone.	11 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in Number of AKs at Week 11	Percentage change from baseline in number of AKs at Week 11	Baseline to week 11
Partial Clearance of AKs at Week 11	Partial clearance of AKs at Week 11, defined as 75% or greater reduction from baseline in the number of clinically visible AKs in the selected treatment area at Week 11	Week 11

Collaborators and Investigators

• Sponsor: LEO Pharma
• Investigators: Principal Investigator: Brian Berman, MD, Ph.D

Publications and helpful links

General Publications

• Berman B, Goldenberg G, Hanke CW, Tyring SK, Werschler WP, Knudsen KM, Larsson T, Swanson N. Efficacy and safety of ingenol mebutate 0.015% gel after cryosurgery of actinic keratosis: 12-month results. J Drugs Dermatol. 2014 Jun;13(6):741-7.
• Berman B, Goldenberg G, Hanke CW, Tyring SK, Werschler WP, Knudsen KM, Goncalves J, Larsson T, Skov T, Swanson N. Efficacy and safety of ingenol mebutate 0.015% gel 3 weeks after cryosurgery of actinic keratosis: 11-week results. J Drugs Dermatol. 2014 Feb;13(2):154-60.

Helpful Links

• Clinical Trials at LEO Pharma

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: February 17, 2012
• First Submitted That Met QC Criteria: February 27, 2012
• First Posted (Estimated): March 1, 2012

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Skin Diseases; Precancerous Conditions; Keratosis, Actinic; Keratosis
• Other Study ID Numbers: LP0041-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO