Ignite Creation Date:
2025-12-24 @ 11:54 PM
Ignite Modification Date:
2026-01-13 @ 7:47 AM
Study NCT ID:
NCT02411851
Status:
COMPLETED
Last Update Posted:
2017-02-01
First Post:
2015-04-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Treatment of Actinic Keratoses (AK) on the Face
Sponsor:
Icahn School of Medicine at Mount Sinai
Organization:
Study Overview
Official Title:
An Investigator-Initiated Study to Assess the Efficacy and Degree of Irritation of Ingenol Mebutate 0.015% Gel and Dermasil Lotion Versus Ingenol Mebuate 0.015% Alone in the Treatment of Actinic Keratoses (AK) on the Face.
Status:
COMPLETED
Status Verified Date:
2017-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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). 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. 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, these localized skin responses (eg erythema, erosion/ulceration, edema, etc.) can often be unpleasant and unsightly. Currently, there are no clinical studies evaluating combination therapies (eg topical steroids, emollients) with ingenol mebutate 0.015% that would decrease irritation and improve wound healing while maintaining efficacy.
Detailed Description:
Actinic keratoses (AK) are common cutaneous lesions associate with chronic ultraviolet radiation exposure. Ultraviolet radiation produces local and systemic immunosuppression, mutations in the p53 tumor suppressor gene, and deoxyribonucleic acid pyrimidine covalent dimmers, each of which is believed to contribute to the dysplasia seen in AK. While most authorities consider AK as a pre-malignant lesion, some consider it as an incipient squamous cell carcinoma (SCC). The risk for progression to SCC for an individual AK is reportedly low but highly variable; however, as patients often have multiple AKs, the overall risk for progression over a lifetime can be significant; thus treatment of AKs is warranted. In addition, the skin around clinically obvious AK lesions has been subject to the same chronic ultraviolet exposure, resulting in genetic damage and mutations, resulting in "field cancerization." Subclinical AKs may progress to clinical AKs, or even de novo invasive SCCs.
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. Treated lesion clearance rates at 3 months post-treatment after double-freeze thaw cryotherapy has been reported to be around 76-88%; however, new lesions in the treatment field were not included. Overall lesion clearance rate, including new subclinical lesions, at approximately 5 months post-cryosurgery has been reported to be 35-51%. The inability to treat subclinical lesions with lesion-directed cryosurgery, has spurred the emergence of topical medications such as ingenol mebutate for field-directed therapy.
Ingenol mebutate is the active compound in the sap from Euphorbia peplus L. (E. peplus). The sap from E. peplus has a long history of community use for the topical treatment of various skin conditions, including AKs. Ingenol mebutate, in a gel formulation referred to as PEP005 (ingenol mebutate) Gel or PEP005 Gel, has been evaluated in clinical trials as field therapy for the topical treatment of AK and photo damaged skin and as lesion-specific treatment for seborrheic keratosis and non-melanoma skin cancer (NMSC). The mechanism of action of ingenol mebutate in AK therapy is not yet fully understood. In vivo and in vitro models have demonstrated both an induction of local lesion cell death and promotion of lesion-specific inflammatory response. A 0.015% topical formulation has been approved for the treatment of AKs in the US as a once a day for three consecutive days regimen. Topical ingenol mebutate treatment may also reduce subclinical lesions in the treatment area, resulting in fewer "new" AK lesions developing over the same period of time when compared to focal treatment.
Phase III data demonstrated complete field clearance of AKs in 37-47% on the face as well as sustained clearance of approximately 50% twelve months post treatment. Similarly a randomized controlled study found a mean reduction of 83% in AK lesions on the face. 87.2% of AK's in the treatment area at baseline were still clear 12 months later. Previous clinical studies report mild to moderate local adverse events (AE) such as pruritus, pain, irritation and local skin response (LSR) (eg erythema, flaking, scaling). The unpleasant and often unsightly localized skin irritation can be emotionally difficulty for patients and provoke anxiety. It is unknown whether a large inflammatory reaction is necessary for successful treatment of actinic keratosis with ingenol mebutate 0.015%. Currently, there are no clinical studies evaluating combination therapies (eg topical steroids, barrier creams, etc.) with ingenol mebutate 0.015% that would decrease irritation while maintaining efficacy.
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. Treated lesion clearance rates at 3 months post-treatment after double-freeze thaw cryotherapy has been reported to be around 76-88%; however, new lesions in the treatment field were not included. Overall lesion clearance rate, including new subclinical lesions, at approximately 5 months post-cryosurgery has been reported to be 35-51%. The inability to treat subclinical lesions with lesion-directed cryosurgery, has spurred the emergence of topical medications such as ingenol mebutate for field-directed therapy.
Ingenol mebutate is the active compound in the sap from Euphorbia peplus L. (E. peplus). The sap from E. peplus has a long history of community use for the topical treatment of various skin conditions, including AKs. Ingenol mebutate, in a gel formulation referred to as PEP005 (ingenol mebutate) Gel or PEP005 Gel, has been evaluated in clinical trials as field therapy for the topical treatment of AK and photo damaged skin and as lesion-specific treatment for seborrheic keratosis and non-melanoma skin cancer (NMSC). The mechanism of action of ingenol mebutate in AK therapy is not yet fully understood. In vivo and in vitro models have demonstrated both an induction of local lesion cell death and promotion of lesion-specific inflammatory response. A 0.015% topical formulation has been approved for the treatment of AKs in the US as a once a day for three consecutive days regimen. Topical ingenol mebutate treatment may also reduce subclinical lesions in the treatment area, resulting in fewer "new" AK lesions developing over the same period of time when compared to focal treatment.
Phase III data demonstrated complete field clearance of AKs in 37-47% on the face as well as sustained clearance of approximately 50% twelve months post treatment. Similarly a randomized controlled study found a mean reduction of 83% in AK lesions on the face. 87.2% of AK's in the treatment area at baseline were still clear 12 months later. Previous clinical studies report mild to moderate local adverse events (AE) such as pruritus, pain, irritation and local skin response (LSR) (eg erythema, flaking, scaling). The unpleasant and often unsightly localized skin irritation can be emotionally difficulty for patients and provoke anxiety. It is unknown whether a large inflammatory reaction is necessary for successful treatment of actinic keratosis with ingenol mebutate 0.015%. Currently, there are no clinical studies evaluating combination therapies (eg topical steroids, barrier creams, etc.) with ingenol mebutate 0.015% that would decrease irritation while maintaining efficacy.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: