Safety and Efficacy of Ingenol Mebutate Gel 0.015% for Treatment of AK on the Face in Solid Organ Transplant Recipients

Study Overview
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Brief Summary
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This is a single arm, open-label interventional study of ingenol mebutate 0.015% in solid organ transplant recipients. The investigators plan to treat 20 subjects, 10 kidney transplant recipients and 10 lung transplant recipients. The investigators have selected these two populations as the represent the spectrum of solid organ transplantation: kidney transplant recipients are the largest transplant population, but have lower levels of immunosuppression and skin cancer risk. Lung transplant recipients have the highest burden of skin cancer and actinic keratoses.

Detailed Description
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Actinic keratoses (AK) are patches of dysplastic keratinocytes arising in sun-damaged skin. These lesions are precursors to cutaneous squamous cell carcinoma (SCC), and are treated to prevent progression to SCC. First-line therapy for AK include cryotherapy and curettage, which target clinically visible lesions but do not address the subclinical lesions in the field of ultraviolet radiation damage. Field therapy includes topical chemotherapy, immunotherapy, and photodynamic therapy. Ingenol mebutate is the active compound found in Euphorbia peplus sap, and has been approved for treatment of AK in immunocompetent patients. Ingenol mebutate 0.015% is favored over other topical treatments for treatment of AK on the face due to the brief treatment course, high clearance rate, and resolution without sequelae. Solid organ transplant recipients (OTR) have a high incidence of AK and high risk of developing SCC, and require frequent field therapy. In addition, OTR generally have a higher burden of AK and require treatment of a larger surface area than the 25 cm2 area labeled for ingenol mebutate 0.015%. The investigators plan to investigate the safety and efficacy of ingenol mebutate 0.015% in OTR, with a treatment area up to 100cm2. This is a single arm, open-label interventional study of ingenol mebutate 0.015% in solid organ transplant recipients. The investigators plan to treat 20 subjects, 10 kidney transplant recipients and 10 lung transplant recipients. The investigators have selected these two populations as the represent the spectrum of solid organ transplantation: kidney transplant recipients are the largest transplant population, but have lower levels of immunosuppression and skin cancer risk. Lung transplant recipients have the highest burden of skin cancer and actinic keratoses.

Official Title
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Safety and Efficacy of Ingenol Mebutate Gel 0.015% for Treatment of Actinic Keratosis on the Face in Solid Organ Transplant Recipients

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: ingenol mebutate gel 0.015%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults at least 18 years old. Subject must be a solid organ transplant recipient at least one year from the date of transplantation. Subjects must be in stable health as confirmed by medical history, per investigator judgement. Subjects must be able to read, sign, and understand the informed consent. Subjects have at least 4 and no more than 20 clinically typical (non-hyperkeratotic/hypertrophic), visible actinic keratoses in a treatment area of approximately 100cm2 on the face. Treatment areas will include a single cheek (nasofacial sulcus to tragus, malar cheekbone to jawline and avoiding the lower eyelid and mouth); the forehead (hairline to eyebrows, extending laterally to the root of the helix). Subject must be willing to forego any other treatments on the face, including cryotherapy, tanning bed use and excessive sun exposure while in the study. Subject is willing and able to participate in the study 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. Exclusion Criteria: Subjects with an unstable medical condition as deemed by the clinical investigator. Subjects with a history of bone marrow or stem cell transplantation. Subjects with non-melanoma skin cancer on the face. Subjects with hyperkeratotic or hypertrophic AKs. 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. Women who are pregnant, lactating, or planning to become pregnant during the study period. Subjects who have previously been treated with ingenol mebutate in study area within the past 8 weeks. Subjects who have used any topical prescription medications for actinic keratosis on the study area within 8 weeks prior to study treatment initiation. Subjects who have used any topical prescription medications for other reason on the study area within 4 weeks prior to study treatment initiation. 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 with known hypersensitivity to Picato gel or any of the inactive ingredients: isopropyl alcohol, hydroxyethyl cellulose, citric acid monohydrate, sodium citrate, or benzyl alcohol.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Open label treatment<br>All patients will be treated with ingenol mebutate gel 0.015%. There is no placebo or comparator for this study. The investigator will identify the patient's treatment area at Baseline, and provide a detailed application instruction sheet. The first dose will be applied in clinic under the supervision of the investigator. | Drug: ingenol mebutate gel 0.015%<br>* ingenol mebutate gel 0.015% to be applied on treatment area<br>* Other names: Picato;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | To evaluate the safety of ingenol mebutate gel 0.015% on the face in solid organ transplant recipients | From screening to Day 57 or study early termination if applicable | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Reduction of Actinic Keratosis | To evaluate the efficacy of ingenol mebutate for reduction of actinic keratoses on the face in organ transplant recipients. | Day 57 (assessed at screening, day 1, day 29, day 57, and study early termination if applicable, clearance at day 57 reported) | 
| Participant's Local Skin Response Grading Scale | To investigate the local skin response to ingenol mebutate in organ transplant recipients. Local skin reaction (LSR) will be graded by visual assessment on a 4 point scale where 0=none, 1=mild, 2=moderate, 3=severe. Each of the following four reactions will be graded: erythema, vesiculation/postulation, crusting/scabbing/erosion, and edema/swelling. A composite score will be calculated (range 0-16). A high LSR indicated a worse outcome. LSR assessment will be performed at days 1, 8, 29, and 84. | Day 1, Day 4 (assessed at screening, day 1, day 4, day 29, day 57, and study early termination if applicable, results at day 1 and day 4 reported) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Actinic Keratosis, lung transplant, kidney transplant