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

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

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.

Study Overview

• Status: Completed
• Conditions: Seborrheic Keratosis
• Intervention / Treatment: Drug: A-101 Vehicle; Drug: A-101 (40) Topical Solution; Drug: A-101 (32.5) Topical Solution

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 172
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Snellville, Georgia, United States, 30078
      • Gwinnett Clinical Research Center, Inc.
  • Michigan
    • Clinton Township, Michigan, United States, 48038
      • Michigan Center for Research Corp.
  • Oregon
    • Portland, Oregon, United States, 97223
      • Oregon Medical Research Center
  • Texas
    • Austin, Texas, United States, 78759
      • DermReseach, Inc.
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • The Education & Research Foundation, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject is at least 18 years of age
2. Subject has a clinical diagnosis of stable clinically typical seborrheic keratosis

3. 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.
4. 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
5. Subject is non-pregnant and non-lactating
6. 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
7. Subject is willing and able to follow all study instructions and to attend all study visits
8. Subject is able to comprehend and willing to sign an Informed Consent Form (ICF).

Exclusion Criteria:

1. Subject has clinically atypical and/or rapidly growing seborrheic keratosis lesions
2. Subject has presence of multiple eruptive seborrheic keratosis lesions (Sign of Leser-Trelat)
3. Subject has a current systemic malignancy
4. Subject has a history of keloid formation or hypertrophic scarring

5. 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

6. 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

7. 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
8. Subject has a history of sensitivity to any of the ingredients in the study medications
9. 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
10. Subject has participated in an investigational drug trial in which administration of an investigational study medication occurred within 30 days prior to Visit 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: A-101 Vehicle; A-101 Vehicle (placebo) Topical Solution	Drug: A-101 Vehicle; Placebo control
Active Comparator: A-101 (40) Topical Solution; A-101 (40) Topical Solution - high dose	Drug: A-101 (40) Topical Solution; A-101 (40) Topical Solution - high dose
Active Comparator: A-101 (32.5) Topical Solution; A-101 (32.5) Topical Solution - low dose	Drug: A-101 (32.5) Topical Solution; A-101 (32.5) Topical Solution - low dose

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aclaris Therapeutics, Inc.
• Investigators: Principal Investigator: Jonathan S Weiss, MD, Gwinnett Clinical Research Center, Inc.; Principal Investigator: Janet Dubois, MD, Derm Research, PLLC; Principal Investigator: David C Wilson, MD, The Education & Research Foundation, Inc.; Principal Investigator: Daniel M Stewart, DO, Michigan Center for Research Corp.; Principal Investigator: Andrew Blauvelt, MD, MBA, Oregon Medical Research Center

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: June 6, 2014
• First Submitted That Met QC Criteria: June 9, 2014
• First Posted (Estimate): June 11, 2014

Study Record Updates

• Last Update Posted (Actual): January 3, 2019
• Last Update Submitted That Met QC Criteria: December 10, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Seborrheic keratosis; A101
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Keratosis, Seborrheic; Pharmaceutical Solutions
• Other Study ID Numbers: A-101-SEBK-202