Clinical trial NCT02716714: Clinical Trial of Ingenol Mebutate Gel 0.015% & 0.05% in Actinic Keratosis
Official title: A Multi-center, OPen, InvEstigator Initiated Phase IV Clinical TRial to Evaluate the Efficacy and SaFety of Ingenol Mebutate Gel 0.015% on Face and Scalp & 0.05% on Trunk and Extremities in KorEan Patient With ACtinic KeraTosis (PERFECT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Actinic Keratosis
Keywords: Korean
Lead sponsor: Korea University
Sponsor class: OTHER
Collaborators: name: LEO Pharma
name: Chonnam National University Hospital
name: Severance Hospital
name: Ajou University School of Medicine
name: Asan Medical Center
name: Samsung Medical Center
name: Seoul National University Bundang Hospital
name: Dong-A University Hospital
name: Korea University Anam Hospital
name: Seoul National University Hospital
First posted: 2016-03-23
Enrollment: 77
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluate the efficacy and safety of ingenol mebutate gel 0.015% on face and scalp \& 0.05% on trunk and extremities in Korean patient with actinic keratosis.

Detailed description: The mechanism of action of ingenol mebutate for actinic keratosis(AK) treatment involves a rapid induction of necrosis followed by neutrophil-mediated, antibody-dependent cellular cytotoxicity (ADCC) of residual lesion. As the ingenol mebutate infiltrates the cell membrane, it increases intracellular Ca2+ concentration which leads to mitochondrial swelling and disruption of mitochondrial membrane within hours. The release of intra-mitochondrial Ca2+ into the cytoplasm leads to depletion of adenosine triphosphate (ATP) and a rapid induction of cell death by necrosis. This process occurs within 1 hour of application, which explains why the treatment period requires only 2 or 3 days of treatment. As the next phase, the cellular necrosis is accompanied by a robust inflammatory response through the release of proinflammatory cytokines from skin cells and tumor cells undergoing necrosis. The release of these proinflammatory cytokines into the dysplastic cells mediates the process of neutrophil recruitment through paracrine signaling and activation of endothelial cells. Here, the neutrophil mediated ADCC occurs, where activated neutrophils attach to the fragment, crystallized (Fc) parts of antibodies of dysplastic cells and destroys the residual dysplastic epidermal cells. In this way, the ingenol mebutate eradicates any residual tumor cells and prevents recurrence of actinic keratosis.As described above, the rapid effect and dual mechanism of action of ingenol mebutate gel allows not only a short-course therapy (2 or 3 days of application) for the elimination of actinic keratosis but also, the benefit for eradication of any residual lesions preventing the recurrence and the progression of AK into squamous cell carcinoma (SCC).

Eligibility criteria: Inclusion Criteria:

1. Male or female aged ≥ 19 years
2. Histopathologically diagnosed AK patients with at least 1 macroscopic and discrete lesion within a contiguous 25 cm2 (e.g. 5 cm x 5 cm) of treatment area
3. The treatment area including the lesion must be accessible to apply the investigational product. However, the lesions on lips, mucosa, outer ear (concha) and those around eyes are excluded.
4. Subjects who signed the written informed consent prior to perform any study-related procedures or assessments, including photographs of their treatment area for documentation and efficacy assessment.

Exclusion Criteria:

1. Hypersensitivity to any components of the investigational product
2. History or evidence of skin conditions that could interfere with evaluation of the investigational product(e.g., eczema, unstable psoriasis, xeroderma pigmentosa, inflammatory or infectious disease around the selected treatment area)
3. Unhealed wound within 5 cm, or basal cell carcinoma or squamous cell carcinoma within 10 cm from the selected treatment area.
4. Subjects who received or expected to receive any of the following pharmacotherapy and non-pharmacotherapy or procedures during the treatment and follow-up period
5. Subjects who have following disorder or abnormal laboratory result
6. Pregnant, lactating, and childbearing potential women who are unwilling to practice effective contraception; for example, oral contraceptives, hormonal methods, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods (i.e., condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), male sterilization, and abstinence.
7. Subjects who previously underwent another clinical trial within 30 days or 5-times the half-life of previous investigational product prior to baseline (the longer period of time must be considered).
8. Other conditions by investigator's discretion to be inappropriate for this clinical study.

Primary outcomes:
measure: CC Rate of AK Lesions in the Selected Treatment Area
timeFrame: at day 57
Secondary outcomes:
measure: Percentage Change of the Number of AK Lesions in the Selected Treatment Area
timeFrame: Baseline and Day 57
measure: Sustained CC Rate in CC Group
timeFrame: at 6 months
measure: Recurrence Rate in CC Group
timeFrame: at 6 months
measure: Percentage Change of the Number of AK Lesions in the Selected Treatment Area of CC Group
timeFrame: at 6 months from baseline
measure: Change From Baseline in Quality of Life (Skindex-29)
timeFrame: at 29 and 57 days from baseline
measure: Treatment Satisfaction Questionnaire for Medication (TSQM)
timeFrame: at 29 and 57 days from baseline
measure: Cosmetic Outcomes Assessment (COA)
timeFrame: at 29 and 57 days from baseline
measure: Time to Relapse in CC Group
timeFrame: at 6 months
Other outcomes:
measure: Medication for Actinic Keratosis
timeFrame: from 57 days to 6 months
measure: Non-Drug Treatment/Surgery for Actinic Keratosis
timeFrame: from 57 days to 6 months
Locations:
city: Ansan-si
country: Korea, Republic of
facility: Korea University Ansan Hospital
state: Gyeonggi-do
Study officials:
affiliation: Korea University Ansan Hospital
name: Ilhwan Kim, MD
role: PRINCIPAL_INVESTIGATOR
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