Ingenol Mebutate 0.015% Gel in the Treatment of Actinic Keratoses (AK) on the Face and Scalp

NCT01836367 | Completed Phase 1 DMC

• 1 other identifier: GCO 13-0026
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Actinic keratoses (AK) are common cutaneous lesions associate with chronic ultraviolet radiation exposure. While most authorities consider AK as a pre-malignant lesion, some consider it as an incipient squamous cell carcinoma (SCC). Among the current therapies for the treatment of AK are excisional surgery, cryosurgery, electrodesiccation and curettage, topical chemotherapy and light therapies. Cryosurgery is considered the gold standard for therapy, however as with other lesion-directed therapies, cryosurgery does not treat subclinical lesions in the surrounding skin. Ingenol mebutate is the active compound in the sap from Euphorbia peplus L. (E. peplus). Topical ingenol mebutate treatment has been approved for the treatment of AKs. The goal of AK therapy for all physicians is to provide an effective, tissue-sparing treatment with good cosmetic results. Ingenol mebutate gel 0.015% has shown to not only have a high clearance rate but also a transient localized inflammatory skin response that resolves quickly without sequelae. However, one common fear about ingenol mebutate is that it's mechanism of action is purely destructive to both AKs and healthy skin, and that retreatment would produce an equally, if not more, caustic result on the skin such as severe erosion, scaling, and erythema. It is our hope to debunk this misconception and demonstrate that reapplication of a second cycle of ingenol mebutate would result in lower LSR scores compared to the LSR in the first cycle of application. We plan to treat 20 subjects. Each qualifying subject will have at least 4-8 non-hypertrophic AKs in a 25 cm2 treatment area on the face or scalp. All subjects will be treated with two cycles of ingenol mebutate 0.015%. The first cycle will be started on Day 1, and the second cycle will be started on Day 29 (four weeks apart). Subjects will utilize the once daily for three days regimen for both cycles.

Conditions

Actinic Keratosis

Keywords

Actinic Keratosis; Face; Scalp; Ingenol Mebutate

Outcome Measures

Primary Outcomes (1)

• Degree of Irritation after two cycles of ingenol mebutate

  To evaluate the degree of irritation, as measured by local skin reactions (LSR), after a second cycle of ingenol mebutate gel to the face or scalp through photography assessed by a blinded observer.

  up to 1 year

Secondary Outcomes (1)

• Degree of Irritation 1 day post application of first and second cycle of ingenol mebutate

  up to 1 year

Study Arms (1)

Ingenol Mebutate 0.015%

EXPERIMENTAL

two cycles of ingenol mebutate 0.015%

Drug: Ingenol Mebutate 0.015%

Interventions

Ingenol Mebutate 0.015% DRUG

Picato

Also known as: ingenol mebutate 0.015% qdaily x 3 days for two cycles

Ingenol Mebutate 0.015%

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults at least 18 years old.
• Subjects must be in good general health as confirmed by the medical history.
• Subjects must be able to read, sign, and understand the informed consent
• Subjects have at least 4-8 clinically typical, visible, non-hypertrophic actinic keratoses on the face or scalp in a 25 cm2 area.
• Subject must be willing to forego any other treatments on the face or scalp, including tanning bed use and excessive sun exposure while in the study.
• Subject is willing and able to participate in the study as an outpatient, making frequent visits to the study center during the treatment and follow-up periods and to comply with all study requirements including concomitant medication and other treatment restrictions.
• If subject is a female of childbearing potential she must have a negative urine pregnancy test result prior to study treatment initiation and must agree to use an approved method of birth control while enrolled in the study.

You may not qualify if:

• Subjects with a history of melanoma anywhere on the body.
• The second cycle of ingenol mebutate 0.015% should only be applied if the skin is healed from the first cycle of ingenol mebutate 0.015%.
• Subjects with an unstable medical condition as deemed by the clinical investigator.
• Subjects with non-melanoma skin cancer on the face or scalp.
• Subjects with any dermatologic disease in the treatment area that may be exacerbated by the treatment proposed or that might impair the evaluation of AKs.
• Subjects who have previously been treated with ingenol mebutate: on the face or scalp in the past 6 months; or outside of the study area within the past 30 days.
• Women who are pregnant, lactating, or planning to become pregnant during the study period.
• Subjects who have experienced a clinically important medical event within 90 days of the visit (e.g., stroke, myocardial infarction, etc).
• Subjects who have active chemical dependency or alcoholism as assessed by the investigator.
• Subjects who have known allergies to any excipient in the study gel.
• Subjects who are currently participating in another clinical study or have completed another clinical study with an investigational drug or device on the study area within 30 days prior to study treatment initiation.
• Subjects who have received any of the following within 90 days prior to study treatment initiation:
• interferon or interferon inducers
• cytotoxic drugs
• immunomodulators or immunosuppressive therapies (inhaled/ intranasal steroids are permitted)

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• LEO Pharma: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Keratosis, Actinic; Facies

Interventions

3-ingenyl angelate

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mark Lebwohl, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairman, Dept of Dermatology

Study Record Dates

• First Submitted: April 17, 2013
• First Posted: April 19, 2013
• Study Start: March 1, 2013
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: December 31, 2013

Record last verified: 2013-12

Locations

US (1)