Study of A-101 for the Treatment of Seborrheic Keratosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and dose-response of 2 concentrations of A-101 versus a vehicle control in the treatment of seborrheic keratosis.

Detailed Description
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The main objective of this study is to evaluate the dose-response relationship of 2 concentrations of A-101 Solution and its matching A-101 Solution Vehicle when applied to seborrheic Keratosis (SK) target lesions on the face. A further objective is to evaluate the safety and efficacy of 2 concentrations of A-101 Solution and its matching A-101 Solution Vehicle when applied topically up to 2 times to SK target lesions on the face.

Official Title
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A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Study of the Dose-Response Profile of A-101 Topical Solution in Subjects With Seborrheic Keratosis of the Face

Conditions
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Seborrheic Keratosis

Intervention / Treatment
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* Drug: A-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is at least 18 years of age Subject has a Fitzpatrick skin type of 1-4 Subject has a clinical diagnosis of stable clinically typical seborrheic keratosis Subject has 1 appropriate seborrheic keratosis target lesion, as defined below (Section 5.4), on the face: Have a clinically typical appearance Be treatment naïve Have a Physician's Lesion Assessment (PLA) of ≥2 (Section 6.1.2) Have a longest axis that is ≥7mm and ≤15mm (Section 5.4) Have a longest dimension perpendicular to the longest axis that is ≥7mm and ≤15mm (Section 5.4) Have a thickness that is ≤2mm Be a discrete lesion Be, when centered in the area outlined by the provided 3cm diameter circular template, the only seborrheic keratosis lesion present Not be on the eyelids Not be within 5mm of the orbital rim Not be covered with hair which, in the investigator's opinion, would interfere with the study medication application or the study evaluations (NB: the study medication may bleach hair) Not be in an intertriginous fold Not be pedunculated. If the subject is a woman of childbearing potential, she has a negative urine pregnancy test and agrees to use an approved effective method of birth control (Section 8) for the duration of the study Subject is non-pregnant and non-lactating Subject is in good general health and free of any known disease state or physical condition which, in the investigator's opinion, might impair evaluation of the target lesion or which exposes the subject to an unacceptable risk by study participation Subject is willing and able to follow all study instructions and to attend all study visits Subject is able to comprehend and willing to sign an Informed Consent Form (ICF). Exclusion Criteria: Subject has clinically atypical and/or rapidly growing seborrheic keratosis lesions Subject has presence of multiple eruptive seborrheic keratosis lesions (Sign of Leser-Trelat) Subject has a current systemic malignancy Subject has a history of keloid formation or hypertrophic scarring Subject has used any of the following systemic therapies within the specified period prior to Visit 1: Retinoids; 180 days Glucocortico-steroids; 28 days Anti-metabolites (e.g., methotrexate); 28 days Subject has used any of the following topical therapies within the specified period prior to Visit 1 on, or in a proximity to the target lesion, which in the investigator's opinion, interferes with the application of the study medication or the study assessments: LASER, light (e.g., intense pulsed light (IPL), photo-dynamic therapy(PDT)) or other energy based therapy; 180 days Retinoids; 28 days Liquid nitrogen, electrodesiccation, curettage, imiquimod, 5-fluorouracil, or ingenol mebutate; 60 days Glucocortico-steroids or antibiotics; 14 days Subject currently has or has had any of the following within the specified period prior to Visit 1 on, or in a proximity to the target lesion, which in the investigator's opinion, interferes with the application of the study medication or the study assessments : A cutaneous malignancy; 180 days Experienced a sunburn; 28 days A pre-malignancy (e.g., actinic keratosis); currently Body art (e.g., tattoos, piercing, etc.); currently Excessive tan; currently Subject has a history of sensitivity to any of the ingredients in the study medications Subject has any current skin disease (e.g., psoriasis, atopic dermatitis, eczema, sun damage, etc.), or condition (e.g., sunburn, excessive hair, open wounds) which, in the investigator's opinion, might put the subject at undue risk by study participation or interfere with the study conduct or evaluations Subject has participated in an investigational drug trial in which administration of an investigational study medication occurred within 30 days prior to Visit 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: A-101 40%<br>A-101 40% Topical Solution | Drug: A-101<br>* Topical Solution<br>|
| Active Comparator: A-101 32.5%<br>A-101 32.5% Topical Solution | Drug: A-101<br>* Topical Solution<br>|
| Placebo Comparator: A-101 Vehicle Topical Solution<br>A-101 0% Topical Solution (vehicle) | Drug: A-101<br>* Topical Solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of PLA Responders With Target Lesion Clear (PLA = 0) in Each Arm at Visit 8. | The primary effectiveness analysis was a comparison between each A-101 group and the vehicle group based on the percentage with target lesions judged to be clear on the PLA (PLA = 0) at Visit 8. The three arms of the study are A-101 40% Topical Solution, A-101 32.5% Topical Solution, and A-101 0% Topical Solution (vehicle). The Physician's Lesion Analysis ( PLA) is a 4 point scale from 0 to 3, with 0 being lesion clear and 3 being the most severe lesion. A larger proportion of subjects with a PLA =0 is better. | Day 106 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline PLA Score at Visit 8 | A secondary efficacy analysis was the mean change from baseline PLA Score at visit 8. The three arms of the study are A-101 40% Topical Solution, A-101 32.5% Topical Solution, and A-101 0% Topical Solution (vehicle). The Physician's Lesion Analysis ( PLA) is a 4 point scale from 0 to 3, with 0 being lesion clear and 3 being the most severe lesion. A larger proportion of subjects with a PLA =0 is better. A lower (more negative) mean change is a better outcome. | Day 106 |