Dose-Response Profile of A-101 in Subjects With Seborrheic Keratosis

Study Overview
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Brief Summary
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The main objective of this study is to evaluate the dose-response relationship of two concentrations of A-101 solution when applied to individual seborrheic keratosis (SK) lesions (target lesions) compared with a matching A-101 Solution Vehicle.

Detailed Description
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The main objective of this study is to evaluate the dose-response relationship of two concentrations of A-101solution when applied to individual seborrheic keratosis (SK) lesions (target lesions) compared with a matching A-101 Solution Vehicle. Each subject will have 4 target lesions on the trunk/extremities. A further objective is to evaluate the safety and efficacy of two concentrations of A-101 solution and its matching vehicle when applied to SK target lesions on the trunk/extremities.

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.

Conditions
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Seborrheic Keratosis

Intervention / Treatment
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* Drug: A-101 Vehicle
* Drug: A-101 (40) Topical Solution
* Drug: A-101 (32.5) Topical Solution


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 clinical diagnosis of stable clinically typical seborrheic keratosis Subject has 4 appropriate seborrheic keratosis target lesions, as defined below, on the trunk/extremities: Have a clinically typical appearance Be treatment naïve Have a Physician Lesion Assessment (PLA) of ≥2 Have a longest axis that is ≥7mm and ≤15mm Have a longest dimension perpendicular to the longest axis that is ≥7mm and ≤15mm 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 in an intertriginous fold Not be in an area where clothing, such as a bra, might cause physical irritation Not be pedunculated. If the subject is a woman of childbearing potential, she has a negative urine pregnancy test and agrees to use an active form of birth control 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 any 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 Glucocorticosteroids; 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, that 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; 90 days Liquid nitrogen, electrodesiccation, curettage, imiquimod, 5-fluorouracil, or ingenol mebutate; 60 days Glucocorticosteroids or antibiotics; 14 days Moisturizers/emollients, sunscreens; 12 hours 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 that, 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) that, in the opinion of the investigator, 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

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 |
| --- | --- |
| Placebo Comparator: A-101 Vehicle<br>A-101 Vehicle (placebo) Topical Solution | Drug: A-101 Vehicle<br>* Placebo control<br>|
| Active Comparator: A-101 (40) Topical Solution<br>A-101 (40) Topical Solution - high dose | Drug: A-101 (40) Topical Solution<br>* A-101 (40) Topical Solution - high dose<br>|
| Active Comparator: A-101 (32.5) Topical Solution<br>A-101 (32.5) Topical Solution - low dose | Drug: A-101 (32.5) Topical Solution<br>* A-101 (32.5) Topical Solution - low dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Per Subject Percentage Target Lesions Judged Clear by the Physician's Lesion Assessment (PLA) | Mean of per-subject percentages of target lesions judged to be clear on the PLA (PLA = 0) at end of study (Visit 8). The PLA is a four point scale from 0 being clear to 3 being most severe lesion. | Baseline, visit 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to Visit 8 in the Physician's Lesion Assessment | Change from baseline PLA will be calculated for each lesion first, then per-subject mean changes from baseline will be calculated. The PLA is a score on a four scale from 0 to 3 with 0 being clear and 3 being the most severe, a lower score indicating a better result. For the mean change in this score, a larger mean change is a better result. | Baseline, visit 8 | 
| Proportion of Subjects Who Had at Least 3 of 4 Target Lesions Judged to be Clear on the Physician Lesion Assessment (PLA =0) at Visit 8. | Proportion of Subjects who had at least 3 of 4 target lesions judged to be clear on the Physician Lesion Assessment (PLA =0) at visit 8. The PLA is a 4 point scale evaluating the severity of a lesion with 0 being clear and 3 being the most severe. | Baseline, visit 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Seborrheic keratosis, A101