Seborrheic Keratosis
Conditions
Keywords
Seborrheic keratosis, A101
Brief summary
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
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.
Interventions
DRUGA-101 Vehicle
Placebo control
DRUGA-101 (40) Topical Solution
A-101 (40) Topical Solution - high dose
DRUGA-101 (32.5) Topical Solution
A-101 (32.5) Topical Solution - low dose
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 No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Per Subject Percentage Target Lesions Judged Clear by the Physician's Lesion Assessment (PLA) | Baseline, visit 8 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Visit 8 in the Physician's Lesion Assessment | Baseline, visit 8 | 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. |
| 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. | 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. The PLA is a 4 point scale evaluating the severity of a lesion with 0 being clear and 3 being the most severe. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A-101 Vehicle A-101 Vehicle (placebo) Topical Solution
A-101 Vehicle: Placebo control | 58 |
| A-101 (40%) Topical Solution A-101 (40%) Topical Solution - high dose
A-101 (40%) Topical Solution: A-101 (40%) Topical Solution - high dose | 57 |
| A-101 (32.5%) Topical Solution A-101 (32.5%) Topical Solution - low dose
A-101 (32.5%) Topical Solution: A-101 (32.5%) Topical Solution - low dose | 57 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Schedule not conducive to study visits | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | A-101 Vehicle | A-101 (40%) Topical Solution | A-101 (32.5%) Topical Solution | Total |
|---|---|---|---|---|
| Age, Customized 18-55 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 56-70 | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Age, Customized 71 + | 56 Participants | 56 Participants | 57 Participants | 169 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 57 Participants | 57 Participants | 171 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fitzpatrick skin type 1 | 4 Participants | 4 Participants | 3 Participants | 11 Participants |
| Fitzpatrick skin type 2 | 13 Participants | 27 Participants | 24 Participants | 64 Participants |
| Fitzpatrick skin type 3 | 30 Participants | 19 Participants | 20 Participants | 69 Participants |
| Fitzpatrick skin type 4 | 11 Participants | 6 Participants | 10 Participants | 27 Participants |
| Fitzpatrick skin type 5 | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Fitzpatrick skin type 6 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 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 | 1 Participants | 0 Participants | 1 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 | 58 Participants | 56 Participants | 57 Participants | 171 Participants |
| Region of Enrollment United States | 58 participants | 57 participants | 57 participants | 172 participants |
| Sex: Female, Male Female | 30 Participants | 33 Participants | 28 Participants | 91 Participants |
| Sex: Female, Male Male | 28 Participants | 24 Participants | 29 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 57 | 0 / 57 |
| other Total, other adverse events | 15 / 58 | 9 / 57 | 17 / 57 |
| serious Total, serious adverse events | 1 / 58 | 0 / 57 | 2 / 57 |
Outcome results
Primary
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.
Time frame: Baseline, visit 8
Population: Overall number of participants = number of participants completing the study per protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A-101 Vehicle | Mean Per Subject Percentage Target Lesions Judged Clear by the Physician's Lesion Assessment (PLA) | 4.82 percentage of lesions cleared | Standard Deviation 15.26 |
| A-101 (32.5%) Topical Solution | Mean Per Subject Percentage Target Lesions Judged Clear by the Physician's Lesion Assessment (PLA) | 26.79 percentage of lesions cleared | Standard Deviation 38.1 |
| A-101 (40%) Topical Solution | Mean Per Subject Percentage Target Lesions Judged Clear by the Physician's Lesion Assessment (PLA) | 45.09 percentage of lesions cleared | Standard Deviation 37.06 |
p-value: 0.0003ANOVA
p-value: 0.0001ANOVA
Secondary
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.
Time frame: Baseline, visit 8
Population: N = number of participants completing the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A-101 Vehicle | Mean Change From Baseline to Visit 8 in the Physician's Lesion Assessment | -0.32 units on a scale | Standard Deviation 0.57 |
| A-101 (32.5%) Topical Solution | Mean Change From Baseline to Visit 8 in the Physician's Lesion Assessment | -0.77 units on a scale | Standard Deviation 0.67 |
| A-101 (40%) Topical Solution | Mean Change From Baseline to Visit 8 in the Physician's Lesion Assessment | -0.91 units on a scale | Standard Deviation 0.77 |
Comparison: mean change from baseline to Visit 8 PLA will be performed using Analysis of Covariance (ANCOVA) with baseline PLA as the covariate.p-value: 0.0001ANCOVA
Comparison: mean change from baseline to Visit 8 PLA will be performed using Analysis of Covariance (ANCOVA) with baseline PLA as the covariate.p-value: 0.0001ANCOVA
Secondary
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.
Time frame: Baseline, visit 8
Population: N = number of subjects who completed the study per protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A-101 Vehicle | 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. | 0 Participants |
| A-101 (32.5%) Topical Solution | 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. | 9 Participants |
| A-101 (40%) Topical Solution | 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. | 11 Participants |
Comparison: Secondary efficacy analyses will also be conducted based on the proportion of subjects who have at least 3 of 4 target lesions judged to be clear on the PLA (PLA=0) at Visit 8.~A separate comparison will be made between each active treatment group and the vehicle treatment group using Cochran-Mantel-Haenszel (CMH) tests stratified by site.p-value: 0.0016Cochran-Mantel-Haenszel
p-value: 0.0004Cochran-Mantel-Haenszel