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

Study Overview
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Brief Summary
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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.

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

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: Ingenol mebutate gel, 0.015%
* Drug: Vehicle gel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ingenol mebutate gel, 0.015%<br>Topical field treatment once daily for 3 consecutive days on the face or scalp | Drug: Ingenol mebutate gel, 0.015%<br>* 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%<br>|
| Placebo Comparator: Vehicle gel<br>Topical field treatment once daily for 3 consecutive days on the face or scalp | Drug: Vehicle gel<br>* 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%<br>|

What is the study measuring?
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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 |