Ingenol Mebutate Gel, 0.015% Repeat Use for Multiple Actinic Keratoses on Face and Scalp

The purpose of the study is to demonstrate that ingenol mebutate gel is efficacious in treating Actinic Keratoses (AKs) present 8 weeks after initial field treatment or emerging in a previously cleared field.

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis
• Intervention / Treatment: Drug: Ingenol mebutate gel, 0.015%; Drug: Vehicle gel

• Study Type: Interventional
• Enrollment (Actual): 463
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Subiaco, Australia, 6008
    • St John of God Dermatology
• Canada
  • Quebec, Canada, G1V 4X7
    • Centre de Recherche Dermatologique
  • Alberta
    • Edmonton, Alberta, Canada, T5K 1X3
      • Stratica Medical
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E8
      • Skin Care Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 1R4
      • Dermadvances Research
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Durondel C.P. Inc./Dermatology Clinic
  • Ontario
    • Barrie, Ontario, Canada, L4M 6L2
      • Ultranova Skincare
    • Peterborough, Ontario, Canada, K9J 1Z2
      • Skin Centre For Dermatology
    • Windsor, Ontario, Canada, N8W 5L7
      • Windsor Clinical Research Inc.
  • Quebec
    • Montreal, Quebec, Canada, H2K 4L5
      • Innovaderm Research Inc.
• France
  • Loire-Atlantique 6
    • Nantes, Loire-Atlantique 6, France, 44000
      • CHU de Nantes
• Germany
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen
• United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Central Manchester University Hosptial

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects must 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 consent to using highly effective methods of contraception

Exclusion Criteria:

• Location of the selected treatment area:

  • on any location other than the face or scalp
  • on the periorbital skin
  • within 5 cm of an incompletely healed wound
  • within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)
• Prior treatment with ingenol mebutate gel on face or scalp (previous treatment on trunk and extremities acceptable)
• Selected treatment area lesions that have atypical clinical appearance
• History or evidence of skin conditions other than the trial indication that would interfere with evaluation of the trial medication in the selected treatment area
• Anticipated need for hospitalization or out-patient surgery prior to Day 15 in the first treatment cycle
• Known sensitivity or allergy to any of the ingredients in ingenol mebutate gel
• Presence of sunburn within the selected treatment area
• Current enrollment or participation in a clinical trial within 30 days of entry into this study
• Subjects previously entered first treatment in the trial
• Female subjects who are breastfeeding
• Subjects who are institutionalised by court order or by the local authority
• In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol

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

• Cosmetic or therapeutic procedures within 2 cm of the selected treatment area
• Use of keratolytic topical therapeutic products within 2 cm of the selected treatment area
• Use of topical medicated creams, ointments, lotions gels, foams or sprays within 2 cm of the selected treatment area; artificial tanners: within 5 cm of the selected treatment area

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

• Treatment with immunomodulators, cytotoxic drugs or interferon /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 Day 1

• Treatment with 5-fluorouracil (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 Day 1

• Use of systemic retinoids or biologic/monoclonal 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: Ingenol mebutate gel, 0.015%; Topical field treatment once daily for 3 consecutive days on the face or scalp	Drug: Ingenol mebutate gel, 0.015%; Topical field treatment once daily for 3 consecutive days within a 25 cm2 treatment area on the face or scalp of AKs present or emerging after an initial treatment with ingenol mebutate gel, 0.015%
Placebo Comparator: Vehicle gel; Topical field treatment once daily for 3 consecutive days on the face or scalp	Drug: Vehicle gel; Topical field treatment once daily for 3 consecutive days within a 25 cm2 treatment area on the face or scalp of AKs present or emerging after an initial treatment with ingenol mebutate gel, 0.015%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Complete Clearance of AKs 8 Weeks After Randomisation	The complete clearance rates 8 weeks after randomisation was compared between ingenol mebutate gel, 0.015% and vehicle gel. Complete clearance was defined as no clinically visible AKs in the Selected Treatment Area (STA)	8 weeks after randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Complete Clearance Through to Month 12, Defined as no Clinically Visible AKs and no Lesions Treated in the Selected Treatment Area at Any Time From Last Treatment Cycle Through to Month 12	The analysis was done separately for the field recalcitrant subgroup, the field recurrent subgroup, and overall for all treated subject (Analysis 1, 2, and 3, respectively)	From last treatment cycle through to Month 12
The Change in AK Count From Randomisation to 8 Weeks After Randomisation	The change in AK count from randomisation to 8 weeks after randomisation was determined for the field recalcitrant and the field recurrent subgroups	8 weeks after randomisation

Collaborators and Investigators

• Sponsor: LEO Pharma
• Investigators: Principal Investigator: Claus Garbe, MD, University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: May 14, 2012
• First Submitted That Met QC Criteria: May 15, 2012
• First Posted (Estimate): May 16, 2012

Study Record Updates

• Last Update Posted (Estimate): May 9, 2016
• Last Update Submitted That Met QC Criteria: April 4, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis
• Other Study ID Numbers: LP0041-22; 2011-005018-13 (EudraCT Number)