Seborrheic Keratosis
Conditions
Brief summary
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
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.
Interventions
DRUGA-101
Topical Solution
Sponsors
Aclaris Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is at least 18 years of age 2. Subject has a Fitzpatrick skin type of 1-4 3. Subject has a clinical diagnosis of stable clinically typical seborrheic keratosis 4. 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. 5. 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 6. Subject is non-pregnant and non-lactating 7. 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 8. Subject is willing and able to follow all study instructions and to attend all study visits 9. 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 * Glucocortico-steroids; 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, 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 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, 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 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) which, in the investigator's opinion, 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of PLA Responders With Target Lesion Clear (PLA = 0) in Each Arm at Visit 8. | Day 106 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline PLA Score at Visit 8 | Day 106 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A-101 40% A-101 40% Topical Solution | 39 |
| A-101 32.5% A-101 32.5% Topical Solution | 39 |
| A-101 Vehicle Topical Solution A-101 0% Topical Solution (vehicle) | 41 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | A-101 40% | A-101 32.5% | A-101 Vehicle Topical Solution | Total |
|---|---|---|---|---|
| Age, Customized Age | 71 years | 71 years | 67 years | 70 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 39 Participants | 41 Participants | 118 Participants |
| Sex: Female, Male Female | 21 Participants | 24 Participants | 20 Participants | 65 Participants |
| Sex: Female, Male Male | 18 Participants | 15 Participants | 21 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 39 | 0 / 39 | 0 / 41 |
| other Total, other adverse events | 13 / 39 | 7 / 39 | 12 / 41 |
| serious Total, serious adverse events | 3 / 39 | 0 / 39 | 1 / 41 |
Outcome results
Primary
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.
Time frame: Day 106
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A-101 40% | Percentage of PLA Responders With Target Lesion Clear (PLA = 0) in Each Arm at Visit 8. | 22 Participants |
| A-101 32.5% | Percentage of PLA Responders With Target Lesion Clear (PLA = 0) in Each Arm at Visit 8. | 18 Participants |
| A-101 Vehicle Topical Solution | Percentage of PLA Responders With Target Lesion Clear (PLA = 0) in Each Arm at Visit 8. | 1 Participants |
p-value: <0.0001Chi-squared
p-value: <0.0001Chi-squared
Secondary
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.
Time frame: Day 106
Population: Participants completing the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A-101 40% | Mean Change From Baseline PLA Score at Visit 8 | -1.7 score on a scale | Standard Deviation 1.11 |
| A-101 32.5% | Mean Change From Baseline PLA Score at Visit 8 | -1.4 score on a scale | Standard Deviation 1.14 |
| A-101 Vehicle Topical Solution | Mean Change From Baseline PLA Score at Visit 8 | -0.1 score on a scale | Standard Deviation 0.56 |
p-value: <0.0001ANCOVA
Comparison: The primary efficacy analysis of mean change from baseline to Visit 8 PLA was performed using analysis of covariance (ANCOVA) with baseline PLA as the covariate. Comparisons between vehicle and each A-101 group were performed within the model using least-squares means and the common error term.p-value: <0.0001ANCOVA