Common Wart
Conditions
Brief summary
Phase 3 Study of A-101 Topical Solution in Subjects with Common Warts
Detailed description
A Phase 3 Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Study of A-101 Topical Solution Applied Twice a Week in Subjects with Common Warts
Interventions
DRUGActive
A-101 45% (hydrogen peroxide 45% topical solution)
OTHERVehicle
Vehicle solution containing isopropyl alcohol and water
Sponsors
Aclaris Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The blinded vehicle solution is packaged to match the active study drug and will be stored under the same conditions.
Intervention model description
Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Study
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject or legal guardian is able to comprehend and is willing to sign an informed consent/assent for participation in this study. 2. Male or female ≥ 2 years old. 3. Subject has a clinical diagnosis of common warts (verruca vulgaris). 4. Subject has at least 1 and up to 6 clearly identifiable common warts located on the trunk or extremities that meet the requirements as defined below: 1. Have a longest axis that is ≥3 and ≤8 mm and have a thickness of ≤3mm 2. Be a discrete lesion, i.e. each wart meeting the entry criteria is clearly separated from other warts. 3. Be present for at least 4 weeks 4. Not be covered with hair which, in the investigator's opinion, would interfere with the study medication treatment or the study evaluations 5. Not be in an intertriginous fold 6. Periungual, subungual, genital, anal, mosaic, plantar, flat and filiform warts are excluded from treatment and evaluation. If a subject has these types of warts, but also has warts that meet the inclusion criteria, the subject will NOT be excluded from the study. 5. Each common wart identified for treatment must have a PWA ≥ 2. 6. Subject's chemistry and complete blood count results are within normal limits. If any of the laboratory values are outside normal range, the treating investigator must assess the value(s) as NOT clinically significant and document this in the subject's medical chart in order for the subject to be eligible for randomization. 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 the evaluation of the identified common warts 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 must be the only individual in a household participating in the study.
Exclusion criteria
1. Subject has clinically atypical common warts. 2. Subject is immunocompromised (e.g., due to chemotherapy, systemic steroids, genetic immunodeficiency, transplant status, etc.). 3. Subject has a history of Human Immunodeficiency Virus (HIV) infection. 4. Subject has had any Human Papilloma Virus (HPV) vaccine within 6 months prior to Visit 1. 5. Subject has used any of the following intralesional therapies within the specified period prior to Visit 2: 1. Immunotherapy (e.g., Candida antigen, mumps antigen, Trichophyton antigen); 8 weeks 2. Anti-metabolite therapy (e.g., bleomycin, 5-fluorouracil); 8 weeks 6. Subject has used any of the following systemic therapies within the specified period prior to Visit 2: 1. Immunomodulatory/immunosuppressant therapy (e.g., etanercept, alefacept, infliximab); 16 weeks 2. Glucocorticosteroids (inhaled and intra-nasal steroids are permitted); 28 days 7. Subject has used any of the following topical therapies within the specified period prior to Visit 2 on, or in the proximity to any of the common warts identified for treatment, that in the investigator's opinion interferes with the study medication treatment or the study assessments: 1. LASER, light or other energy-based therapy (e.g., intense pulsed light \[IPL\], photodynamic therapy \[PDT\]); 180 days 2. Immunotherapy (e.g., imiquimod, squaric acid dibutyl ester\[SADBE\], etc.) 12 weeks 3. Liquid nitrogen, electrodesiccation, curettage; 60 days 4. Hydrogen peroxide; 90 days 5. Antimetabolite therapy (e.g., 5-fluorouracil); 8 weeks 6. Retinoids; 90 days 7. Over-the-counter (OTC) wart therapies and cantharidin; 28 days 8. Subject currently has or has had any of the following within the specified period prior to Visit 1 on or in the proximity to any of the common warts identified for treatment that, in the investigator's opinion, interferes with the study medication treatment or the study assessments: 1. Cutaneous malignancy; 180 days 2. Sunburn; currently 3. Pre-malignancy (e.g., actinic keratosis); currently 9. Subject has a history of sensitivity to any of the ingredients in the study medications. 10. Subject has any current skin or systemic disease (e.g., psoriasis, atopic dermatitis, eczema, sun damage), 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. 11. Participation in another therapeutic investigational drug/device trial in which administration of an investigational treatment occurred with 30 days prior to Visit 1. 12. Subject has an active malignancy. 13. Subjects is viewed by the Principal Investigator as not being able to complete the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60) | Day 60 | The primary efficacy endpoint is the number of subjects whose identified common warts are determined to be clear on the Physician Wart Assessment (PWA) scale (PWA=0) at Visit 10 (Day 60). Efficacy will be assessed using the Physician's Wart Assessment Scale (PWA) which is a 4 point scale. A higher amount of warts cleared represents a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137) | Day 137 | Number of subjects whose identified common warts are determined to be clear on the Physician Wart Assessment (PWA) scale (PWA=0) at Visit 13 (Day 137). Efficacy will be assessed using the Physician's Wart Assessment Scale (PWA) which is a 4 point scale. A higher amount of warts cleared represents a better outcome. |
| Mean Per-Subject Percent of All Warts That Were Clear on the Physician Wart Assessment (PWA) Scale Between Active and Vehicle That Are Clear (PWA=0) at Visit 13 (Day 137) | Day 137 | Mean Per-Subject Percent of all Warts that were Clear on the Physician Wart Assessment (PWA) scale between Active (A-101 45%) and Vehicle that are clear (PWA=0) at Day 137. Clearance of all treated warts will be assessed using the Physician Wart Assessment (PWA) scale which is a four point scale. A higher amount of warts cleared represents a better outcome. |
| Number of Subjects With a Single Wart at Baseline Whose Wart Was Clear on the PWA Scale Between Active and Vehicle Group (PWA=0) at Visit 10 (Day 60) | Day 60 | Comparison between Active (A-101 45%) and Vehicle of subjects with a single wart at baseline, whose wart is clear (PWA=0) at Day 60. Clearance of the single wart at baseline will be assessed using the Physician Wart Assessment (PWA) scale which is a four point scale. A higher amount of warts cleared represents a better outcome. |
| Median Time for Subjects to Achieve Clearance (PWA=0) of All Treated Common Warts | Day 137 | Comparison between Active (A-101 45%) and Vehicle with respect to the median time to achieve onset of clearance (PWA=0) for all treated warts at Day 137. Clearance of all treated warts will be assessed using the Physician Wart Assessment (PWA) scale which is a four point scale. A higher amount of warts cleared represents a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Topical solution, hydrogen peroxide 45%
A-101: hydrogen peroxide 45% topical solution | 251 |
| Vehicle Topical solution, isopropyl alcohol and water
Vehicle: Vehicle solution containing isopropyl alcohol and water | 251 |
| Total | 502 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator Decision | 2 | 2 |
| Overall Study | Lost to Follow-up | 16 | 12 |
| Overall Study | Withdrawal by Subject | 9 | 17 |
Baseline characteristics
| Characteristic | Active | Vehicle | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 75 Participants | 70 Participants | 145 Participants |
| Age, Categorical >=65 years | 7 Participants | 13 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 169 Participants | 168 Participants | 337 Participants |
| Age, Continuous | 31.1 years STANDARD_DEVIATION 17.8 | 31.7 years STANDARD_DEVIATION 17.33 | 31.4 years STANDARD_DEVIATION 17.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 35 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 206 Participants | 199 Participants | 405 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 22 Participants | 17 Participants | 39 Participants |
| Fitzpatrick Skin Type I - Always Burns | 9 Participants | 14 Participants | 23 Participants |
| Fitzpatrick Skin Type II - Burns Easily | 93 Participants | 91 Participants | 184 Participants |
| Fitzpatrick Skin Type III - Burns Moderately | 87 Participants | 83 Participants | 170 Participants |
| Fitzpatrick Skin Type IV - Burns Minimally | 42 Participants | 41 Participants | 83 Participants |
| Fitzpatrick Skin Type VI - Never Burns | 7 Participants | 8 Participants | 15 Participants |
| Fitzpatrick Skin Type V - Rarely Burns | 13 Participants | 14 Participants | 27 Participants |
| Longest Axis of Largest Wart Treated | 5.1 millimeter STANDARD_DEVIATION 1.54 | 5.1 millimeter STANDARD_DEVIATION 1.55 | 5.1 millimeter STANDARD_DEVIATION 1.55 |
| Prior Treatment of any Wart Treated No | 137 Participants | 139 Participants | 276 Participants |
| Prior Treatment of any Wart Treated Yes | 114 Participants | 112 Participants | 226 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 13 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) White | 228 Participants | 230 Participants | 458 Participants |
| Region of Enrollment United States | 251 participants | 251 participants | 502 participants |
| Sex: Female, Male Female | 104 Participants | 111 Participants | 215 Participants |
| Sex: Female, Male Male | 147 Participants | 140 Participants | 287 Participants |
| Thickness of Largest Wart Treated | 1.49 millimeters STANDARD_DEVIATION 0.741 | 1.50 millimeters STANDARD_DEVIATION 0.752 | 1.49 millimeters STANDARD_DEVIATION 0.746 |
| Time since First Appearance of Least Recent Wart Treated | 1926.2 days STANDARD_DEVIATION 2298.39 | 1780.0 days STANDARD_DEVIATION 2037.01 | 1853.5 days STANDARD_DEVIATION 2171.47 |
| Time Since First Appearance of Most Recent Wart Treated | 1726.7 days STANDARD_DEVIATION 2210.95 | 1670.2 days STANDARD_DEVIATION 2041.81 | 1698.6 days STANDARD_DEVIATION 2126.62 |
| Total Warts Treated 1 | 126 Participants | 142 Participants | 268 Participants |
| Total Warts Treated 2 | 68 Participants | 49 Participants | 117 Participants |
| Total Warts Treated 3 | 22 Participants | 18 Participants | 40 Participants |
| Total Warts Treated 4 | 13 Participants | 14 Participants | 27 Participants |
| Total Warts Treated 5 | 10 Participants | 10 Participants | 20 Participants |
| Total Warts Treated 6 | 12 Participants | 18 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 251 | 0 / 251 |
| other Total, other adverse events | 154 / 251 | 61 / 251 |
| serious Total, serious adverse events | 1 / 251 | 2 / 251 |
Outcome results
Primary
The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60)
The primary efficacy endpoint is the number of subjects whose identified common warts are determined to be clear on the Physician Wart Assessment (PWA) scale (PWA=0) at Visit 10 (Day 60). Efficacy will be assessed using the Physician's Wart Assessment Scale (PWA) which is a 4 point scale. A higher amount of warts cleared represents a better outcome.
Time frame: Day 60
Population: The study's primary endpoint was to evaluate the amount of patients achieving a clearance of all baseline WARTS. Patients were stratified by the amount of WARTS at Baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active | The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60) | Warts at Baseline - 1 | 19 Participants |
| Active | The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60) | Warts at Baseline - 3 | 3 Participants |
| Active | The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60) | Warts at Baseline - 2 | 9 Participants |
| Active | The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60) | Warts at Baseline - >3 | 2 Participants |
| Active | The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60) | Warts at Baseline - All | 33 Participants |
| Vehicle | The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60) | Warts at Baseline - >3 | 4 Participants |
| Vehicle | The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60) | Warts at Baseline - All | 8 Participants |
| Vehicle | The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60) | Warts at Baseline - 1 | 4 Participants |
| Vehicle | The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60) | Warts at Baseline - 2 | 0 Participants |
| Vehicle | The Primary Efficacy Endpoint is the Number of Subjects Whose Identified Common Warts Are Determined to be Clear on the PWA Scale (PWA=0) at Visit 10 (Day 60) | Warts at Baseline - 3 | 0 Participants |
Comparison: A summary of the wart clearance at Visit 10.p-value: 0.000195% CI: [2.14, 10.76]Mixed Models Analysis
Secondary
Mean Per-Subject Percent of All Warts That Were Clear on the Physician Wart Assessment (PWA) Scale Between Active and Vehicle That Are Clear (PWA=0) at Visit 13 (Day 137)
Mean Per-Subject Percent of all Warts that were Clear on the Physician Wart Assessment (PWA) scale between Active (A-101 45%) and Vehicle that are clear (PWA=0) at Day 137. Clearance of all treated warts will be assessed using the Physician Wart Assessment (PWA) scale which is a four point scale. A higher amount of warts cleared represents a better outcome.
Time frame: Day 137
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Mean Per-Subject Percent of All Warts That Were Clear on the Physician Wart Assessment (PWA) Scale Between Active and Vehicle That Are Clear (PWA=0) at Visit 13 (Day 137) | 27.7 percentage of warts cleared | Standard Deviation 2.3 |
| Vehicle | Mean Per-Subject Percent of All Warts That Were Clear on the Physician Wart Assessment (PWA) Scale Between Active and Vehicle That Are Clear (PWA=0) at Visit 13 (Day 137) | 12.2 percentage of warts cleared | Standard Deviation 2.3 |
p-value: <0.000195% CI: [9, 21.8]Wilcoxon (Mann-Whitney)
Secondary
Median Time for Subjects to Achieve Clearance (PWA=0) of All Treated Common Warts
Comparison between Active (A-101 45%) and Vehicle with respect to the median time to achieve onset of clearance (PWA=0) for all treated warts at Day 137. Clearance of all treated warts will be assessed using the Physician Wart Assessment (PWA) scale which is a four point scale. A higher amount of warts cleared represents a better outcome.
Time frame: Day 137
Population: A median was not able to be calculated in the Vehicle group due to an insufficient number of participants with events.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active | Median Time for Subjects to Achieve Clearance (PWA=0) of All Treated Common Warts | 113 days |
| Vehicle | Median Time for Subjects to Achieve Clearance (PWA=0) of All Treated Common Warts | NA days |
p-value: <0.0001Log Rank
Secondary
Number of Subjects With a Single Wart at Baseline Whose Wart Was Clear on the PWA Scale Between Active and Vehicle Group (PWA=0) at Visit 10 (Day 60)
Comparison between Active (A-101 45%) and Vehicle of subjects with a single wart at baseline, whose wart is clear (PWA=0) at Day 60. Clearance of the single wart at baseline will be assessed using the Physician Wart Assessment (PWA) scale which is a four point scale. A higher amount of warts cleared represents a better outcome.
Time frame: Day 60
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Number of Subjects With a Single Wart at Baseline Whose Wart Was Clear on the PWA Scale Between Active and Vehicle Group (PWA=0) at Visit 10 (Day 60) | 19 Participants |
| Vehicle | Number of Subjects With a Single Wart at Baseline Whose Wart Was Clear on the PWA Scale Between Active and Vehicle Group (PWA=0) at Visit 10 (Day 60) | 4 Participants |
p-value: 0.000695% CI: [1.76, 15.53]Wilcoxon (Mann-Whitney)
Secondary
Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137)
Number of subjects whose identified common warts are determined to be clear on the Physician Wart Assessment (PWA) scale (PWA=0) at Visit 13 (Day 137). Efficacy will be assessed using the Physician's Wart Assessment Scale (PWA) which is a 4 point scale. A higher amount of warts cleared represents a better outcome.
Time frame: Day 137
Population: The study's primary endpoint was to evaluate the amount of patients achieving a clearance of all baseline WARTS. Patients were stratified by the amount of WARTS at Baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active | Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137) | Warts at Baseline - 1 | 29 Participants |
| Active | Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137) | Warts at Baseline - 3 | 5 Participants |
| Active | Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137) | Warts at Baseline - 2 | 12 Participants |
| Active | Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137) | Warts at Baseline - >3 | 10 Participants |
| Active | Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137) | Warts at Baseline - All | 56 Participants |
| Vehicle | Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137) | Warts at Baseline - >3 | 8 Participants |
| Vehicle | Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137) | Warts at Baseline - All | 25 Participants |
| Vehicle | Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137) | Warts at Baseline - 1 | 13 Participants |
| Vehicle | Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137) | Warts at Baseline - 2 | 2 Participants |
| Vehicle | Number of Subjects With Complete Clearance of All Treated Common Warts Between Active and Vehicle on the Physician Wart Assessment (PWA) Scale (PWA=0) at Visit 13 (Day 137) | Warts at Baseline - 3 | 2 Participants |
Comparison: P-Value test comparing the Patients Cleared of All Baseline Warts in the Active (A-101 45%) and vehicle groups.p-value: 0.000195% CI: [1.61, 4.56]Mixed Models Analysis