Clinical trial NCT03691831
Conditions: Common Wart
Sponsor: Aclaris Therapeutics, Inc.
Start date: 2018-09-13; Completion date: 2019-07-09
Enrollment: 502 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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

Arms: arm 1: A-101 45% (Topical solution, hydrogen peroxide 45%) arm 2: Topical solution, isopropyl alcohol and water
Interventions: intervention 1: Active intervention 2: Vehicle
Intervention descriptions: intervention 1: A-101 45% (hydrogen peroxide 45% topical solution) intervention 2: Vehicle solution containing isopropyl alcohol and water

Protocol documents:
SAP_002.pdf: 
26 September 2019
Statistical Analvsis Plan
Acl餌is Therapeutics lnc.
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STATISTICAL ANALYSIS PLAN ­ TEXT
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VEHICLE­CONTROLLED, PARALLEL GROUP STUDY OF A­101
TOP重CAL SOI,UT賞ON APPLIED TWIC田A WEEK IN SUBJECTS
WITH COMMON WARTS
Protocol:　　A­1 0 1 ­WARIL302
StudyDrug: A­101
¯ Sponsors:　Aclaris Therapeutics;Inc.
¯∇erSibn (Date) : ¯I5xt丁2 (26­Septeinber 2IT19)
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Rebecca DeMoor: Principal Statistician
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D如e:　090CT2019
Pageしof25


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Statistical Analysis Plan 
 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ............................ 4 
1. 
STUDY OBJECTIVES .................................................................................. 5 
1.1 Primary Objective ............................................................................................. 5 
1.2 Secondary Objectives ........................................................................................ 5 
2. 
STUDY DESIGN ........................................................................................... 5 
3. 
STATISTICAL METHODS ........................................................................... 9 
3.1 Study Populations, Disposition, Baseline Characteristics, 
Medical History Concomitant Medications, Exposure and 
Protocol Violations ...................................................................................... 9 
3.1.1 
Analysis Populations ...................................................................... 9 
3.1.2 
Subject Disposition and Discontinuation from Study .................... 9 
3.1.3 
Wart Diagnosis and Characteristics at Baseline ........................... 10 
3.1.4 
Prior and Concomitant Medications, Therapies and 
Procedures .................................................................................... 10 
3.1.5 
Protocol Violations ....................................................................... 10 
3.2 Efficacy Endpoints .......................................................................................... 10 
3.2.1 
Complete Clearance of All Warts ................................................. 11 
3.2.2 
Sensitivity Analyses for the Primary Endpoint ............................ 12 
3.2.3 
Secondary Efficacy Endpoints ..................................................... 13 
3.2.4 
Mean Per Subject Percent of Warts Cleared ................................. 13 
3.2.5 
Complete Clearance in Subjects with a Single Wart 
at Baseline .................................................................................... 14 
3.2.6 
Time to Clearance of All Warts .................................................... 14 
3.2.7 
Subgroup Analyses of Efficacy .................................................... 15 
3.3 Safety Analyses ............................................................................................... 16 
3.3.1 
Extent of Exposure ....................................................................... 16 
3.3.2 
Adverse Events ............................................................................. 16 
3.3.3 
Local Skin Reactions .................................................................... 17 
3.3.4 
Vital Signs .................................................................................... 17 
3.3.5 
Laboratory Evaluations ................................................................ 17 
3.4 Interim Analyses .............................................................................................. 18 
3.5 Sample Size ..................................................................................................... 18 
3.6 Changes in/ Clarifications to the Conduct of the Study or 
Planned Analysis ....................................................................................... 18 
4. 
STATISTICAL SOFTWARE ....................................................................... 20 
5. 
REFERENCES............................................................................................. 20 
APPENDIX A:  MULTIPLE IMPUTATION AND TIPPING POINT 


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ANALYSES ................................................................................................. 21 
APPENDIX B:  ASSIGNMENT TO ANALYSIS VISIT ..................................... 24 
APPENDIX C:  SIMULATION DETAILS FOR POWER 
COMPUTATION ......................................................................................... 25 
 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
 
Abbreviation 
Term 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
ANOVA 
Analysis of Variance 
CBC 
Complete Blood Count 
CMH 
Cochran-Mantel-Haenszel 
CPH 
Cox Proportional Hazards 
CRF 
Case Report Form 
FCS 
Fully Conditionally Specified 
ID 
Identification 
ITT 
Intent to Treat 
LSR 
Local Skin Reactions 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple Imputation 
PHREG 
SAS Procedure for Proportional Hazards Regression 
PP 
Per Protocol 
PT 
Preferred Term 
PWA 
Physician’s Wart Assessment 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Alan 
SOC 
System Organ Class 
US 
United States 


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INTRODUCTION 
 
The purpose of this statistical analysis plan (SAP) is to provide a description of the 
statistical analyses performed for the Phase 3 protocol, A-101-WART-302, Amendment 2, 
Version 4 (12Oct2018). 
1. 
STUDY OBJECTIVES 
1.1 Primary Objective 
The primary objective of this study is to evaluate the effectiveness of A-101 45% 
compared to Vehicle when applied twice weekly to common warts. 
1.2 Secondary Objectives 
The secondary objectives of this study include: 
• 
Duration of response to A-101 45% compared to Vehicle. 
• 
Onset of action of A-101 45% compared to Vehicle. 
• 
Safety of A-101 45%. 
2. 
STUDY DESIGN 
This is a phase 3, multicenter, randomized vehicle controlled, double blind parallel 
group study to evaluate the safety and efficacy of A-101 45% vs Vehicle in subjects 
with common warts. Investigators will be required to identify at least 1 and up to 6 
clearly identifiable common warts for treatment with A-101 study medication. All 
identified common warts will be treated twice a week for up to 8 weeks (maximum of 
16 treatment applications). Subjects will be required to complete a total of 13 study 
visits. The protocol defined study visits are: 
 
• 
Visit 1 (Day -13 to 0) screening 
• 
Visit 2 (Day 1)* randomization; study medication treatment 
• 
Visit 3 (Day 8)* study medication treatment 
• 
Visit 4 (Day 15)* study medication treatment 
• 
Visit 5 (Day 22)* study medication treatment 
• 
Visit 6 (Day 29)* study medication treatment 
• 
Visit 7 (Day 36)* study medication treatment 
• 
Visit 8 (Day 43)* study medication treatment 
• 
Visit 9 (Day 50)* study medication treatment 
• 
Visit 10 (Day 60) follow up evaluations, no identified Wart retreatment 
• 
Visit 11 (Day 78) follow up evaluations, no identified Wart retreatment 
• 
Visit 12 (Day 106) follow up evaluations, no identified Wart retreatment 
• 
Visit 13 (Day 137) follow up evaluations, no identified Wart retreatment; end of 
study 
*The second weekly application will be applied by the subject/parent/legal guardian at 
home (Day 4, 11, 18, 25, 32, 39, 46, and 53). 
Approximately 500 subjects will be randomized to one of 2 treatment arms in a 1:1 ratio 


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at approximately 25 investigational centers in the US. Of the 500 subjects randomized, 
approximately 100 subjects will be between 1 and 17years of age.  
 
 
The study schedule of assessments can be found in Table 1.A. 


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Schedule of Assessments 
Visit 
V1 
Screening 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
Treatment Day 
-13 to 0 
1 
8 
15 
22 
29 
36 
43 
50 
60 
78 
106 
137 
Treatment Window 
N/A 
N/A 
±1 
day 
±1 
day 
±1 
day 
±1 
day 
±1 
day 
±1 
day 
±1 
day 
+4 
days 
±7 
days 
±7 
days 
+7 
days 
Study Procedures 
Informed Consent 
▲ 
Inclusion Criteria/Exclusion Criteria 
▲ 
▲1 
Subject Identifier 
▲2 
Medical history/demographics 
▲ 
Fitzpatrick Skin Type Assessment 
▲3 
Vital Signs 
▲4 
▲ 
▲ 
Prior Medications/Therapies 
▲5 
Clinical Chemistry and CBC6 
▲ 
▲ 
Common Wart Identification7 
▲ 
Physician’s Wart Assessment8 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Common Wart Dimensions9 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Standardized Photography10 
▲ 
▲11 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Subject Randomization 
▲12 
Local Skin Reactions 
▲13 
▲13 
▲13 
▲13 
▲13 
▲13 
▲13 
▲ 
▲ 
▲ 
▲ 
▲ 
Study Medication Application14 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Study Medication Application at 
Home15 
A-101 Study Medication will be applied at home on Days 4, 
11, 18, 25, 32, 39, 46, 53. A window of +1 day is allowed.  
Subject Instructions 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Concomitant therapies16 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Adverse Events17 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
 
See Footnotes starting on next page. 


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1Subject inclusion/exclusion criteria will be re-assessed prior to randomization during Visit 2. 
2Investigational sites will assign a unique five-digit subject identifier to each subject at Visit 1. This subject identifier will be used in all study documentation for the duration 
of the study. 
3Each subject’s skin must be assessed during Visit 1 using the Fitzpatrick Skin Type Assessment. 
4Vital signs [including temperature, pulse, respiratory rate, blood pressure, height and weight (Visit 1 only)] will be measured by a qualified staff member at Visit 1, Visit 9 
and Visit 13. 
5Prior medications/therapies will be collected for a time-period of 14 days prior to Visit 2.  
6A complete blood count (including hematocrit, hemoglobin, platelet count, red blood cell count and morphology, white blood cell count and differential (absolute and %) 
including basophils, eosinophils, lymphocytes, monocytes and neutrophils and a clinical chemistry panel including albumin, alkaline phosphatase, alanine aminotransferase 
(ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), bicarbonate, calcium, chloride, creatinine, glucose, lactate dehydrogenase (LDH), phosphorus, 
potassium, sodium, total bilirubin, total protein, and uric acid. 
7The treating investigator will identify at least 1 and up to 6 common warts located on the trunk or extremities that meet the inclusion criteria. 
8 The investigator will use the Physician Wart Assessment (PWA) scale to assess each identified common wart. The investigator must assess the identified common warts 
prior to application of the study medication at Visit 2-Visit 9. In order to be eligible for randomization at Visit 2, each common wart must have a PWA grade ≥ 2. 
9 The investigator will measure the dimensions (longest axis and thickness of the common wart) at Visit 1 and prior to randomization at Visit 2. The investigator will be 
required to measure the longest axis of each common wart at Visits 2-13. 
10 At Visits 1, Visit 2, 4, 6, and 9 (prior to study medication application), and Visit 10-13, a qualified investigational center staff member will take a photograph of each 
identified common wart using the Aclaris supplied camera. All photographs will be sent to a central imaging laboratory. 
11At a sub-set of investigational sites (up to 3 sites), subjects randomized at these sites will have additional standardized photographs taken of their common warts at the 
following time-points: V2-10 minutes post application, 1-hour post application and 24 hours post application. 
12Subjects will be randomized at Visit 2 prior to application of study medication. Investigational study staff will re-confirm subject eligibility prior to randomization. 
13 The investigator and subject will assess each identified common wart for local skin reactions associated with irritation at Visits 2-13. At Visit 2-Visit 9, the investigator and 
subject will assess each identified common wart for LSRs prior to the application of the study medication.  
14 During in-office visits, subjects 18 years of age and older will apply their A-101 study medication in the presence of the treating physician or a member of the 
investigational study staff that has been trained on the protocol. Subjects ages 1 to 17 will have their A-101 study medication applied by a parent/legal guardian in front of the 
treating physician or a member of the investigational study staff during in-office visits. If the identified common wart meets the criteria for re- treatment the lesion will be re-
treated at Visits 3-9. Following application of study medication, subjects must NOT wash/submerge the treated wart for at least 6 hours and they must NOT apply any topical 
products to the treated common warts for at least 6 hours. Parents/legal guardians of children must ensure that the child does not put the treated area in their mouth, or eyes, 
until completely dry after the application. If the treated area is not completely dry 10 minutes after the application, the area should be blotted dry. 
15All subjects will receive their second weekly treatment of the A-101 study medication at home on Days 4, 11, 18, 25, 25, 32, 39, 46, 53 as determined by the PWA 
assessment performed during the in-office visit. Subjects ages 1 to 17 will have their A-101 study medication applied by a parent or legal guardian. All subjects will need to 
document the application of A-101 study medication in a subject diary. The second weekly treatment will depend on the PWA performed during the in-office visit that week. 
If the identified common wart meets the criteria for re-treatment during the in-office visit, then the subject/parent/guardian will perform the second weekly treatment at home. 
16All concomitant therapies including (topical and oral) prescription medications, over the counter medications and natural supplements and non-drug therapies including 
chiropractic, physical therapy, and energy-based therapy must be documented in the subject CRF. Subjects must not apply any topical products (e.g., moisturizers, sunscreen, 
etc.) to the identified common wart within 12 hours prior to any study visit. 
17The reporting period for Serious Adverse Events (SAEs) begins when the subject signs the informed consent and continues through Visit 11. Non-serious clinical adverse 
events will be collected following the application of the study medication at Visit 2 and through Visit 11. Non-serious adverse events that occur between the time of consent 
and study medication application will be documented as medical history. All safety reporting (AEs and SAEs) will conclude at Visit 11 (approximately 28 days after last 
study medication application) except for clinical adverse events related to local skin reactions. 


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3. 
STATISTICAL METHODS  
The Intent-to-Treat Population (ITT) will be used for primary and secondary efficacy 
analyses and summaries.  The Per-Protocol (PP) population will be used for sensitivity 
analyses for the primary efficacy analysis and all secondary efficacy analyses included in 
the hierarchical testing procedure (Figure 1).  Subjects will be summarized and analyzed 
according to randomized treatment group for efficacy. The Safety Population will be used 
for safety analyses. Subjects will be summarized according to actual treatment received at 
first application of study medication for safety.  
The baseline scores for PWA will be the last non-missing value collected ≤ the date of the 
first application of double-blind study medication.  
For the purpose of analysis, data will be assigned to an analysis visit based on relative 
study day as defined in Appendix B.   
All Data listings will be sorted by randomized treatment group and subject ID. 
3.1 Study Populations, Disposition, Baseline Characteristics, Medical History 
Concomitant Medications, Exposure and Protocol Violations 
3.1.1 Analysis Populations 
The populations used for analyses will be defined as follows: 
• Intent-to-Treat Population (ITT): The ITT population includes all randomized 
subjects.  
• Per-Protocol Population (PP):  The PP Population includes all subjects who 
received at least one application of study medication and had no protocol 
violations as defined in Section 3.1.6. 
• Safety Population: The Safety population includes all subjects who received at 
least one application of study medication. 
3.1.2 Subject Disposition and Discontinuation from Study 
The number of subjects screened, randomized and treated will be presented together with 
the study completion status and the reasons for discontinuation grouped by treatment 
and by major reason (lost to follow-up, adverse event, poor compliance etc.).  
A listing will be provided of all patients discontinued from the study after enrolment, 
broken down by center and treatment group, giving a patient identifier, the specific 
reason for discontinuation, the treatment (drug and dose), and the duration of treatment 
before discontinuation. Whether or not the blind for the patient was broken at the time of 
discontinuation will be noted. Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be presented in the data listings.  


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Descriptive summary statistics (n, mean, standard deviation, median, minimum, and 
maximum) and/or frequency distributions, as appropriate, will be generated by 
randomized treatment group and combined.   
3.1.3 Wart Diagnosis and Characteristics at Baseline 
Descriptive summary statistics (n, mean, standard deviation, median, minimum, and 
maximum) and/or frequency distributions, as appropriate, will be generated by 
randomized treatment group and combined.  Summarized variables include total warts 
treated, time since first appearance of most and least recent treated warts, longest axis of 
largest wart treated, and thickness of largest wart treated. 
3.1.4 Prior 
and 
Concomitant 
Medications, 
Therapies 
and 
Procedures 
Medications are coded using the WHO Drug (March 2019).  Prior and concomitant 
medications are listed only.  The period(s) in which the medications were administered 
will be flagged. 
3.1.5 Protocol Violations 
Protocol violations will be identified prior to database lock to measure adherence to key 
aspects the protocol (see section 16.2 of the protocol for full definitions).    Specific data 
fields that will be examined to identify protocol violations include entrance 
inclusion/exclusion criteria and prohibited prior and concomitant medications as well as 
all deviations identified by the investigator. All protocol violations will be listed by 
patient number and summarized (n and percent) by randomized treatment group. 
3.2 Efficacy Endpoints 
The primary efficacy analysis will evaluate the effectiveness of A-101 45% compared to 
Vehicle at the endpoint visit, Visit 10 (Day 60). It will be based on the proportion of 
subjects who achieve complete clearance (PWA=0) of all treated common warts.  
Four secondary efficacy analyses will be performed and tested in a hierarchical Fixed-
Sequence step-down method to control alpha among the pre-specified secondary efficacy 
variables. The predefined order of the tests is specified to be the order of these analyses 
as presented below (Figure 1). All analyses will be conducted at the same alpha level (2-
tail alpha = 0.05). The results of the second analysis will only be reported if the first 
analysis reaches statistical significance at alpha = 0.05.  The results of the third analysis 
will only be reported if the first and second analyses reach statistical significance, each at 
alpha = 0.05. The results of the fourth analysis will only be reported if the first, second 
and third analyses reach statistical significance, each at alpha = 0.05.  


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Figure 1 
Hierarchical Testing of Primary and Secondary Endpoints to 
Maintain Study-Wise Type I error at α=0.05 (2-Sided) 
 
For regulatory purposes, testing for will halt at the first endpoint with P> 0.05, however 
all endpoints will be analyzed irrespective of the results. Supportive and sensitivity 
analyses of the primary and secondary endpoints will also be performed. 
Should sparse enrollment at one or more sites occur, the following algorithm will be 
employed to “pool” sites for analysis. Sites with fewer than 5 subjects randomized will be 
pooled by ordering the sites based on the number of subjects randomized and the site 
number (in the event multiple sites have the same number randomized) and then 
combining the smallest with the next smallest site in the sort order in a stepwise fashion 
until all the sites/pooled sites have more than 4 subjects.  A pooled site can be pooled 
again if, after an initial pooling, it remained part of the smallest or next smallest site or 
pooled site.  In the sort order when there are ties in count, a “pooled site” comes after 
non-pooled sites in the pooling hierarchy. The pooled site(s) will be used in all analyses 
that are stratified by site and/or include site in the statistical model.   
3.2.1 Complete Clearance of All Warts 
The primary efficacy analysis will evaluate the effectiveness of A-101 45% compared to 
Vehicle at the endpoint visit, Visit 10 (Day 60). It will be based on the proportion of 
subjects who achieve complete clearance (PWA=0) of all treated common warts. A 


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Statistical Analysis Plan 
 
 
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Cochran-Mantel-Haenszel (CMH) test stratified by the baseline number of treated warts 
(1 wart, 2 warts, 3 warts, >3 warts) will be used to perform the primary efficacy 
comparison between treatment groups, with 2-tail alpha set at 0.05. Any treated common 
wart for a randomized subject that has missing data at the endpoint visit will be treated as 
not clear for the purpose of the primary efficacy analysis. Corresponding estimates of the 
common Mantel-Haenszel odds ratio will be provided along with 95% confidence 
intervals (CIs).  Stratum specific odds ratio estimates and 95% confidence intervals will 
also be provided. 
Syntax for the SAS statements used to perform the analysis will be consistent with 
respect to the statistics calculated in the following: 
PROC FREQ; 
TABLE WARTS*TREATMENT*RESPONSE/CMH; 
OUTPUT OUT=STATS (KEEP=P_CMHGA  _MHOR_ L_MHOR  U_MHOR  P_BDCHI) CMH; 
Where WARTS represents the number of warts assessed at baseline (1 wart, 2 warts, 3 
warts, >3 warts); TREATMENT is 1 for A-101 and 2 for Vehicle; and RESPONSE = 1 
for those with all warts cleared and 2 for those without all warts cleared. P_CMHGA is 
the CMH general association test, _MHOR_ is the Mantel-Haenszel estimated common 
odds ratio, and L_MHOR and U_MHOR are the lower and upper limits, respectively, of 
the corresponding 95% confidence interval.  P_BDCHI is the p-value from the Breslow-
Day test of the homogeneity of the odds ratios across strata and is provided as a 
supportive statistic to assess the model.  A statistically significant finding (P<0.05) of the 
Breslow-Day test indicates that the treatment effect differs by stratum and these 
differences should be investigated by stratum-specific odds ratios estimates which will be 
included in the output for the primary endpoint.  
3.2.2 Sensitivity Analyses for the Primary Endpoint 
The first sensitivity analysis for the primary endpoint will be an analysis based upon the 
PP population.  This analysis will use the same CMH model described for the primary 
analysis. 
A second sensitivity analysis will be conducted for the primary endpoint using the same 
CMH model for the ITT population that includes the imputation of missing PWA data 
using a fully conditionally specified (FCS) regression-based Multiple Imputation (MI) 
procedure.  This regression-based MI will be conducted on the worst (maximum) PWA 
score for all treated warts at a given visit for each subject.  The utilization of the FCS 
methodology accounts for the correlation within a subject and models mean changes over 
time in the maximum PWA score.  For each subject, only data selected as representative 
of an analysis visit (i.e. within the defined relative day range and closest to the “target”) 
as documented in Appendix B are included in the imputation process.  The imputed data 
will be in the form of the maximum PWA score and will be rounded to an integer and 
bounded by 0 below and 3 above.  All imputed maximum PWA scores that are assigned a 
0 will correspond to complete clearance of all warts at that visit.  The complete clearance 
at visit 10 using this MI data will be analyzed using the same CMH model described for 


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the primary analysis.  Results from the CMH on the MI data will then be summarized 
using the Wilson-Hilferty3 transformation to obtain the sensitivity results primary 
efficacy endpoint.  The SAS syntax used to perform the MI and the MI summary is 
shown in Appendix A 
To assess the impact of missing data imputation on primary analysis results a tipping 
point analysis will be conducted.  This analysis will shift the treatment coefficient in the 
regression model used in the MI procedure to impose a worse mean maximum PWA for 
the A-101 45% arm and a better mean maximum PWA for the vehicle arm.  The shifts 
will be from 0 to 3 in increments of 0.5 for the A-101 45% arm and from 0 to -3 in 
increments of 0.5 for the vehicle arm.  Apart from these tipping point shifts, the analysis 
will follow the same methodology described for the MI procedure. The odds ratio and 
CMH Chi-square P-value are provided for each of the 7 x 7 =49 shift combinations for 
the two arms. 
In addition, a model similar to the primary analysis model but stratified instead by Study 
Center will be performed as a sensitivity analysis including the Breslow-Day test to 
evaluate heterogeneity across sites.  The SAS syntax differs only by replacing the 
WARTS in the above example with SITE where site may be a “pooled site” as detailed in 
section 3.2. 
3.2.3 Secondary Efficacy Endpoints 
Visit 13 (Day 137) will be analyzed using an identical model as the primary endpoint at 
Visit 10 (Day 60).  This will be the first secondary endpoint tested in the hierarchy of 
endpoints described in Section 3.2.  This analysis will be run on the ITT population using 
randomized treatment group.  
 
Sensitivity analyses performed for the primary endpoint will be repeated for the Visit 13 
analysis.  These sensitivity analyses will include the PP analysis, missing data imputation 
impact analyses, and the tipping point analysis.  The site heterogeneity analysis will not 
be performed. 
3.2.4 Mean Per Subject Percent of Warts Cleared 
Mean per-subject percent of warts cleared at Visit 13 (Day 137) will be evaluated as the 
second secondary endpoint using analysis of covariance (ANCOVA) with treatment 
group as a class variable and the baseline number of warts assessed as a continuous 
covariate.  Patents without a week Visit 13 measurement according to the assignment to 
analysis visit in Appendix B will be assigned a score of 0% warts cleared.  Ninety-five 
percent confidence intervals will be constructed about the estimated treatment difference 
based on the model estimates and associated variability. 
 
Syntax for the SAS statements used to perform the analysis will be consistent with 
respect to the statistics calculated in the following: 
PROC GLM: 
CLASS TREATMENT; 


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26 September 2019 
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Statistical Analysis Plan 
 
 
CONFIDENTIAL 
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MODEL PER_CLEAR = TREATMENT WARTS / SOLUTION CLPARM; 
LSMEANS TREATMENT / PDIFF STDERR ALPHA=0.05 CL E; 
ESTIMATE ‘A-101 vs Vehicle’ TREATMENT 1 -1 / CL; 
 
Where WARTS represents the number of warts assessed at baseline; TREATMENT is 1 
for A-101 and 2 for Vehicle; and PER_CLEAR is the mean per subject percent of warts 
cleared.  
 
A separate sensitivity analysis for the mean per-subject percent of warts cleared will be 
conducted using the PP population. 
3.2.5 Complete Clearance in Subjects with a Single Wart at Baseline 
A Cochran Mantel Haenszel (CMH) test stratified by investigative site will be used to 
compare treatment groups with respect to the proportion whose wart is Clear (PWA=0) at 
Visit 10 in the subset of ITT subjects with a single wart at baseline. This is the third 
secondary endpoint in hierarchy summarized in section 3.2. 
Syntax for the SAS statements used to perform the analysis will be consistent with 
respect to the statistics calculated to the following: 
PROC FREQ; 
TABLE SITE*TREATMENT*RESPONSE/CMH; 
OUTPUT OUT=STATS (KEEP=P_CMHGA _MHOR_ L_MHOR  U_MHOR  P_BDCHI) CMH; 
Where SITE may be a “pooled site” as detailed in Section 3.2 and the other terms are as 
detailed in Section 3.2.1. 
A sensitivity analysis for the complete clearance in subjects with a single wart at baseline 
will be conducted in the subset of the PP subjects with a single wart at baseline. 
3.2.6 Time to Clearance of All Warts 
The fourth secondary endpoint tested, the difference in time to clearance of all warts from 
randomization between the two treatment arms, is assessed in the ITT population using 
the stratified log-rank test (Score statistic from PHREG and ties=Breslow) from a Cox 
proportional hazards (CPH) model including treatment and the number of warts assessed 
at baseline in the model. Survival for each arm is summarized using Kaplan Meier curves 
and is further characterized in terms of the median and survival probability at selected 
timepoints, along with the corresponding 2-sided 95% confidence intervals for the 
estimates. Confidence intervals for median survival are based upon the methods of 
Brookmeyer and Crowley1. Confidence intervals for survivorship estimates are calculated 
using the log-log transformation2.   
Syntax for the SAS statements used to perform the analysis will be consistent with 
respect to the statistics calculated to the following: 
PROC PHREG; 
MODEL DAYSFOL*RESPONSE(2) = TREATMENT / RISKLIMITS TIES=BRESLOW; 


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STRATA  WARTS; 
 
Where WARTS represents the number of warts assessed at baseline (1 wart, 2 warts, 3 
warts, >3 warts); TREATMENT is 1 for A-101 and 0 for Vehicle; and RESPONSE = 1 
for those with all warts cleared and 2 for those without all warts cleared. Subjects without 
complete clearance (i.e. RESPONSE = 2) are censored on the date of the last wart 
assessment.  DAYSFOL = Date of last wart(s) assessment – date randomized +1. Patients 
without a post baseline assessment are censored on date of randomization. The Wald Chi-
Square P-value is used. 
 
Kaplan-Meier estimates for plotting and for estimates of median and of the survivorship 
curve at selected times (Days from Randomization) will be obtained using SAS statements 
consistent with the following syntax: 
 
PROC LIFETEST ALPHA=.05; 
TIME DAYSFOL*RESPONSE(2); 
SURVIVAL OUT=SURV CONFTYPE=LOGLOG; 
STRATA TREATMENT; 
A sensitivity analysis for the time to clearance of all warts will be conducted on the PP 
population. 
3.2.7 Subgroup Analyses of Efficacy 
Exploratory subgroup analyses of the primary and secondary endpoints will be performed. 
Descriptive statistics will be provided by treatment group.  Odd Ratios for wart clearance 
and hazard ratio for time to wart clearance will also be presented. The following 
subgroups will be assessed: 
• Age (<18, ≥18) 
• Sex (Male, Female) 
• Race (White, Non-White) 
• Maximum PWA at Baseline (2,3) 
• Fitzpatrick Skin Type (I, II, III, IV, V, VI) 
• Number of treated warts  (1 wart, 2 warts, 3 warts, >3 warts) 
• Subjects <18 years old with 4 or more treated warts 
 
Additionally, an analysis of wart clearance according to wart location will be performed 
using the individual warts as the experimental unit (i.e. the denominator).  Five location 
categories are defined as follows based upon the grid locations as recorded on the CRF: 


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Subgroup 
Grid Locations 
Hands 
'A4', 'D4', 'E4', 'H4' 
Feet 
'B6', 'C6', 'F6', 'G6' 
Elbows 
'A3', 'D3', 'E3', 'H3' 
Knees 
'B5', 'C5', 'F5', 'G5' 
Rest of Body 
All locations not included in above 4 categories 
 
3.3 Safety Analyses 
Safety summaries will be conducted on the Safety Population and use actual treatment 
received.    
The following sections detail the summaries performed on the safety data. Additional 
data handling rules including those for imputation of partially missing dates are provided 
in a separate SAP document pertaining to data handling and programming specifications. 
The baseline scores for vital signs, laboratory assessments and local skin reactions will be 
the last non-missing value collected ≤ the date of the first application of double-blind 
study medication.  
3.3.1 Extent of Exposure 
The duration of treatment, the number of application days (i.e. the actual count of days 
where an application occurred), the mean applications per wart (for each subject the sum 
of all applications across all treated warts and all application days divided by the total 
number of treatments for all treated warts), and the total applications will be summarized 
using descriptive statistics (n, mean, SD, median, minimum and maximum). The 
percentage of total wart treatments that were performed in 1, 2 or 3 applications is also 
provided. 
Overall compliance is calculated as the number total number of warts treated for the 
treatment period (through date of last application to any wart) divided by the total number 
of warts expected to be treated. The total number of warts treated is the sum of the 
retreatment and home application diary records completed times the number of warts 
assessed at baseline minus the number of warts scored as PWA=0 or having an LSR 
grade 3 at the most recent assessment (<= the date of the application). 
3.3.2 Adverse Events 
Adverse events are coded using the MedDRA (Version 22) dictionary and are categorized 
by system organ class (SOC) and preferred term (PT).  Only treatment emergent adverse 
events are included in summary tabulations (i.e. adverse events occurring on or after the 
first application of study medication and within 30 days following the last application of 
study medication). All adverse events are included in the data listings including those that 
are not considered treatment emergent.   


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To allow differentiation as to which study period an Adverse Event occurred, three 
categories are defined based upon onset date. Adverse Events that had onset dates prior to 
the first application of study medication are considered "prior”. Adverse events with 
onset dates on or after the first application of double-blind study medication and within 
30 days following the last application of study medication are considered “treatment 
emergent”.  Events with onset dates more than 30 days after the last application of study 
medication are considered as "post-therapy".   
   
Frequency tabulations are presented by MedDRA SOC and preferred term, for all adverse 
events; study treatment-related, adverse events resulting in discontinuation of study 
treatment, serious adverse events and adverse events by maximum severity. Adverse 
events resulting in discontinuation are those with ‘action taken’ recorded as ‘drug 
withdrawn’. 
 
Treatment emergent adverse event summaries by MedDRA SOC and preferred term will 
also be provided according to the following subgroups: 
 
• Age (<18, 18 to 65, and >65) 
• Sex (Male, Female) 
• Race (White, Non-White) 
 
3.3.3 Local Skin Reactions 
The number of subjects with local skin reaction signs that worsened by at least 1 grade 
from baseline any time after the first application of study medication will be tabulated 
according to treatment group for each sign as well any sign. A separate summary limited 
to LSRs that worsen and which occur within 30 days of the last application of study 
medication will be provided.  The number of subjects with local skin reaction signs that 
worsened by at least 1 grade from baseline any time after the first application of study 
medication will be tabulated by treatment group and Fitzpatrick Skin Type for each sign 
as well as any sign. 
3.3.4 Vital Signs 
Systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate and 
temperature are summarized using descriptive statistics for each visit. Both actual values 
and changes from baseline will be summarized. 
3.3.5 Laboratory Evaluations 
Shift tables showing changes in relationship to the normal reference range grade from 
baseline to the “worst” relationship recorded post-baseline are tabulated.  In the event a 
subject had both “low” and “high” post-baseline values the subject will be counted under 
both “low” and “high”.  As such, the percentages of the cells in the shift table may add to 
more than 100%.   
Chemistry and hematology parameters are summarized using descriptive statistics for 


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each visit. Both actual values and changes from baseline will be summarized. 
The number and percentage of subjects meeting criteria for hepatobiliary abnormalities 
will be provided. 
3.4 Interim Analyses 
No interim analyses are planned for this study. 
3.5 Sample Size 
Based on efficacy results from study A-101-WART-203 with the same active study 
medication and treatment plan specified in the current protocol for a comparable subject 
population and indication, an overall per-wart clearance rate of at least 26% for Active 
compared with 9% for Vehicle is anticipated. Assuming a distribution of treated warts per 
subject comparable to the Phase 2 study results, statistical modeling provided a forecast 
of an advantage in subject responder rates (all treated warts with PWA=0) for Active over 
Vehicle groups of at least 11 percentage points. This leads to a required sample size for 
the current study of approximately 500 subjects to provide greater than 90% power to 
achieve statistical significance in the primary efficacy analysis. This projection takes into 
account the impact of the anticipated subject dropout rate on power for the primary 
efficacy analysis, based on the Intent-to-Treat (ITT) population and planned missing data 
imputation procedures. 
Additionally, a simulation was conducted in a manner that accounted for the distribution 
of multiple warts, the treatment effect in clearance between the different warts and the 
correlation in wart clearance among multiple warts.  Specific details of the simulation are 
described in Appendix C.  Results of this simulation indicate that data from 500 subjects 
(250 per group) will provide 97% power to demonstrate the superiority of 45% A-101 
topical solution over vehicle for the primary endpoint.    
3.6 Changes in/ Clarifications to the Conduct of the Study or Planned 
Analysis 
The secondary endpoint of mean per subject percent of warts decreased will be analyzed 
by an analysis of covariance (ANCOVA) including, in addition to the treatment, terms for 
baseline number of warts as a continuous covariate and study site as a class variable.  The 
protocol mentioned only analysis of variance (ANOVA) with specifying the treatment 
term to be included in the model. 
A Breslow-Day test of the homogeneity of the odds rations across strata for the analysis 
of the primary endpoint – i.e. across the strata defined by the number of warts assessed at 
baseline – is added to assess the model.  
A PP Population has been added to test the sensitivity of the primary and select secondary 
analyses to major violations in the protocol. 
A “Safety Population” has been added that will be used for all safety summaries as 


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opposed to the ITT Population mentioned in the protocol.  Safety analyses will be 
performed according to actual treatment received at the first application in the event of 
dosing error(s). 
An error in Section 3.2.4 in version 1.1 of the SAP was corrected where the text in the 
first sentence incorrectly indicated that site was class variable in the model.  The SAS 
syntax in this same section did not include site and reflects the intended analysis.  Site 
has been removed from the first sentence in Version 1.2.  This correction was performed 
after unblinding the study.  An Ad Hoc analysis with the inclusion of site confirmed that 
there is no meaningful difference between the two models.  


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4. 
STATISTICAL SOFTWARE 
All data summaries and listings will be performed using SAS Version 9.4 or higher, 
under Windows operating system. 
5. 
REFERENCES 
1. Brookmeyer and Crowley, A Confidence Interval for the Median Survival Time, 
Biometrics 38, 29-41, March 1982. 
 
2.   Kalbfleisch, J. D. and Prentice, R. L. (1980), The Statistical Analysis of Failure Time 
      Data, New York: John Wiley & Sons, Inc. 
 
3.   Wilson, E. H. (1931). The distribution of chi-squared. National Academy of Sciences,  
      (pp. 684-688). Washington. 


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APPENDIX A:  MULTIPLE IMPUTATION AND TIPPING POINT 
ANALYSES 
This appendix details the syntax used to perform the sensitivity analyses described in 
section 3.2.1 of the SAP.  The syntax is consistent with SAS version 9.4. 
proc mi data=PWAtran seed=123 nimpute=20 out=MIout maximum=3 minimum=0 
round=1; 
   class TREATMENT; 
   fcs reg(PWAV2= PWAV8 PWAV9 PWAV10 PWAV13 WartN TREATMENT /details); 
   fcs reg(PWAV8= PWAV2 PWAV9 PWAV10 PWAV13 WartN TREATMENT /details); 
   fcs reg(PWAV9= PWAV8 PWAV2 PWAV10 PWAV13 WartN TREATMENT /details); 
   fcs reg(PWAV10= PWAV8 PWAV9 PWAV2 PWAV13 WartN TREATMENT /details); 
   fcs reg(PWAV13= PWAV8 PWAV9 PWAV10 PWAV2 WartN TREATMENT /details); 
   var PWAV2 PWAV8 PWAV9 PWAV10 PWAV13 TREATMENT WARTN;  
run;  
 
*** PWAV2 PAWV8 PWAV9 PWAV10 PWAV10 PWAV11 PWAV12 and PWAV13 *** 
*** represent the maximum of PWA scores from all warts assessed ***    
*** at baseline and analysis visits 8 through 13 as defined in ***       
*** Appendix B. WARTN is the number of warts assessed at baseline ***; 
 
**** Assign Response and Strata ****; 
 
data MIresp; 
  set MIout; 
  if PWAV10 =0 then response=1; 
  else response=2; 
  WARTS=wartN; 
  if WARTS gt 3 then WARTS=4;  ** Greater than 3 warts **;  
 
proc sort; 
  by _imputation_; 
 
*** Obtain Mantel-Haenszel estimate of the common odds ratio and General 
Association Statistic adjusted for baseline score category ***; 
PROC FREQ DATA=MIresp; 
TABLES WARTS*TREATMENT*RESPONSE / CMH; 
output out=stats cmh; 
BY _Imputation_; 
 
DATA OR;  
  SET stats; 
  *** Log-transform odds ratio estimates and obtain standard error from 
confidence intervals ***; 
  log_or_mh_value=log(_MHOR_); 
  log_or_mh_se=(log(U_MHOR)-log(L_MHOR))/(2*1.96); 
  *** Apply Wilson-Hilferty transformation to the CMH statistic and 
standardize the resulting normal variable; 
  cmh_value_wh= 
  ((_CMHGA_/DF_CMHGA)**(1/3) - (1-2/(9*DF_CMHGA)))/SQRT(2/(9*DF_CMHGA)); 
  cmh_sterr_wh = 1.0; 
  *** Apply Wilson-Hilferty transformation to the Breslow Day statistic 
and standardize the resulting normal variable ****; 


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  BD_value_wh= 
  ((_BDCHI_/DF_BDCHI)**(1/3) - (1-2/(9*DF_BDCHI)))/SQRT(2/(9*DF_BDCHI)); 
  BD_sterr_wh = 1.0; 
 
*** Combine transformed OR estimates; 
PROC MIANALYZE DATA=OR; 
ODS OUTPUT PARAMETERESTIMATES=LOG_EST; 
MODELEFFECTS log_or_mh_value; 
STDERR log_or_mh_se; 
 
*** Back-transform OR combined values; 
DATA BACKTRANS;  
   SET LOG_EST; 
   Estimate_back = EXP(ESTIMATE); *Pooled odds ratio; 
   LCL_back=Estimate_back*EXP(-1.96*STDERR); *Pooled lower limit; 
   UCL_back=Estimate_back*EXP(+1.96*STDERR); *Pooled upper limit; 
 
*** Combine CMH General Association Results; 
PROC MIANALYZE DATA=OR; 
ODS OUTPUT PARAMETERESTIMATES=cmh_wh; 
MODELEFFECTS cmh_value_wh; 
STDERR cmh_sterr_wh; 
 
*** Compute combined CMH P-value as one-sided p-value from normal test 
from MIANALYZE ***; 
DATA cmh_wh_p;  
SET cmh_wh; 
IF tValue > 0 THEN ProbCMH = Probt/2; 
ELSE ProbCMH = 1-Probt/2; 
 
*** Combine Breslow-Day Results; 
PROC MIANALYZE DATA=OR; 
ODS OUTPUT PARAMETERESTIMATES=bd_wh; 
MODELEFFECTS bd_value_wh; 
STDERR bd_sterr_wh; 
 
*** Compute combined Breslow-Day P-value as one-sided p-value from 
normal test from MIANALYZE ***; 
DATA bd_wh_p;  
SET bd_wh;  
IF tValue > 0 THEN ProbBD = Probt/2; 
ELSE ProbBD = 1-Probt/2; 
 
****** Calculate Binomial Response Rates *****; 
 
data MIresp2; 
  set MIresp; 
  output; *** For each Stata ***; 
  Warts=9; 
  output; *** All Strata combined ***; 
 
** Create Dummy Data that has all both responder and non-responders **; 
***** for each strata and treatment but weight will be zero **********; 
proc sort data=miresp2 nodupkey out=trt_strat(keep=treatment warts 
_imputation_); 


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by treatment warts _imputation_; 
 
data zeros; 
  set trt_strat; 
  wt=0; 
  Response=1; output; 
  Response=2; output; 
 
**** Add the Zero Weight Records to the Data ***; 
data MIrespWT; 
  set MIresp2 zeros; 
  if wt=. then wt=1; 
 
proc sort; 
  by treatment warts _imputation_; 
 
PROC FREQ DATA=MIrespWT; 
TABLES RESPONSE / BINOMIAL; 
output out=Bin_prop binomial; 
BY treatment warts _Imputation_; 
*** Use zeros option in weight statement ***; 
weight wt/zeros; 
 
*** Combine proportion estimates ***; 
proc means data=bin_prop; 
  by treatment warts; 
  var N _bin_; 
  output out=Prop mean=N Prop; 
 
data Props; 
   set Prop; 
   *** Calculate Estimated Number of Responders (Does not need to be an 
integer) ***; 
   N_Resps=N*Prop; 
 
data All; 
  merge props(keep=TREATMENT WARTS N Prop N_Resps) 
        backtrans(keep=Estimate_back lcl_back ucl_back)  
        cmh_wh_p(keep=ProbCMH) 
        bd_wh_p (keep=ProbBD); 
 
 
label 
 
 
TREATMENT='Treatment Arm' 
        WARTS='Number of Warts at Baseline (9=All Levels)' 
        N='Subjects' 
        N_Resps='n Responders' 
        Prop='Proportion Responders' 
        estimate_back='MH OR' 
        LCL_back='Lower Limit MH OR' 
        UCL_back='Upper Limit MH OR' 
        ProbCMH='CMH P-Value' 
        ProbBD='Breslow-Day P-Value'; 
run; 


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APPENDIX B:  ASSIGNMENT TO ANALYSIS VISIT 
Due to the possibility of deviation from the protocol schedule as well as to incorporate 
data from unscheduled and/or early termination visits, analysis visits are defined below 
based on relative study day.  These analysis visits are based on the nominal, scheduled 
visits in the protocol but allow for wider windows (more days around the target study 
day).  Analysis visit will be used in analyses performed by or on specific visit as well as 
for the identifiers on data listings.  Both nominal visits as collected on the CRF and 
analysis visits will be retained in the SAS ADaM datasets. 
 
Analysis Visit 
Study Day Range 
Target Study Day 
V3 – Day 8 
2 - 11 
8 
V4 – Day 15 
12 - 18 
15 
V5 – Day 22 
19 - 25 
22 
V6 – Day 29 
26 - 32 
29 
V7 – Day 36 
33 - 39 
36 
V8 – Day 43 
40 - 46 
43 
V9 – Day50 
47 - 53 
50 
V10 – Day 60 
54 - 69 
60 
V11 – Day 78 
70 - 97 
78 
V12 – Day 106 
98 - 121 
106 
V13 – Day 137 
≥122 
137 
In the event that more than one observation falls into the same study day range, the value 
closest to the “target day” is selected.  If there’s a tie in the absolute distance from the 
target day, the observation with the greater cycle day is selected.   


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APPENDIX C:  SIMULATION DETAILS FOR POWER COMPUTATION 
A 27-parameter multinomial distribution was used to simulate the primary endpoint in the 
Phase 3 WART studies.  The 27 parameters corresponding to the 27 possibilities for the 
number of warts that are cleared at Visit 10 is shown in Table 2. 
 
Table 2: Grid of 27-Parameters Corresponding to the Number of Possible Warts Cleared 
Number 
Cleared 
Number of Treated Warts 
1 
2 
3 
4 
5 
6 
0 
X1 
X3 
X6 
X10 
X15 
X21 
1 
X2 
X4 
X7 
X11 
X16 
X22 
2 
 
X5 
X8 
X12 
X17 
X23 
3 
 
 
X9 
X13 
X18 
X24 
4 
 
 
 
X14 
X19 
X25 
5 
 
 
 
 
X20 
X26 
6 
 
 
 
 
 
X27 
 
The probability estimates for the multinomial parameters were derived from a Bayesian 
posterior Dirichlet distribution that resulted from updating a non-informative Jeffreys 
conjugate prior with the data from the A101-WART-203 Visit 10 data.  Random 
probability estimates were drawn from the Bayesian posterior distribution for each of the 
10,000 simulations.  Then a random event was drawn from the 27-parameter multinomial 
using simulation specific probabilities for each of the 10,000 simulations. 
 
In each individual simulation, the number of warts cleared in the first (1 baseline wart), 
second (2 baseline warts) and third (3 baseline warts) strata were obtained from X2, X5 
and X9, respectively, as defined in the grid in Table 2.  The number of cleared warts in 
the 4th striatum was obtained from the sum of X14, X20 and X27.  The odds ratio 
between A101 45% and vehicle was tested using a CMH stratified by these 4 strata.  The 
number of positive simulation results divided by the total number of simulations was 
used to compute power. 

Prot_001.pdf: 
Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
1  
 
CLINICAL STUDY PROTOCOL 
Protocol Number: A-101-WART-302 
 
THWART 2: 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 
Version 1.0:  21May2018 
Version 2.0: 09July2018 
FINAL Protocol:  Amendment 1 Version 3: 11 September 2018 
Amendment 2 Version 4: 12 October 2018 
Amendment 3 Version 5: 14 February 2019 
Sponsor 
Aclaris Therapeutics, Inc. 
640 Lee Road, Suite 200 
Wayne, PA 19087 
Telephone: (484) 324-7933 
Facsimile: (484) 320-2344 
Study Contact 
Judy Schnyder 
Telephone:  484-329-2144 
Cell Phone:  484-999-7448 
Email:  jschnyder@aclaristx.com 
Medical Monitor 
David Gordon, MD 
Chief Medical Officer 
Aclaris Therapeutics, Inc. 
Telephone:  484-540-6273 
Email:  dgordon@aclaristx.com 
Serious Adverse Event Facsimile:  484-324-2359 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
2  
 
 
This document is a privileged and confidential communication of Aclaris Therapeutics, Inc. Acceptance of this document 
constitutes an agreement by the recipient that no unpublished information contained herein will be used, published or disclosed 
without prior written approval from Aclaris Therapeutics, Inc 




Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
4  
 
INVESTIGATOR’S AGREEMENT 
Protocol Number:  A-101-WART-302 
Protocol Title:  THWART 2: 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 
Protocol Version  
Version 5 14 February 2019 
I have reviewed the above-titled protocol and agree that it contains all the information necessary to conduct the 
study as required.  I will conduct the trial in accordance with the principles of ICH Good Clinical Practice and the 
Declaration of Helsinki. 
I will maintain as confidential all written and verbal information provided to me by the Sponsor, including but not 
limited to, the protocol, case report forms, investigator’s brochure, material supplied at investigator meetings, 
minutes of teleconferences, etc.  Such material will only be provided as necessary to site personnel involved in the 
conduct of the trial, involved IRBs or local regulatory authorities. 
I will obtain written informed consent/assent from each prospective trial subject or each prospective trial subject’s 
legal representative prior to conducting any protocol-specified procedures.  The Informed Consent 
Document/Assent Document used will have the approval of the IRB appropriate for my institution. 
I will maintain adequate source documents and record all observations, treatments and procedures pertinent to trial 
patients in their medical records.  I will accurately complete the case report forms supplied by the Sponsor in a 
timely manner.  I will ensure that my facilities and records will be available for inspection by representatives of the 
Sponsor, the IRB, and/or local regulatory authorities.  I will ensure that I and my staff are available to meet with 
Sponsor representatives during regularly scheduled monitoring visits. 
I will notify the Sponsor immediately of any serious adverse events.  Following this notification, a written report 
describing the serious adverse event will be provided to the Sponsor as soon as possible, but no later than five days 
following the initial notification. 
 
 
 
 
Investigator Name (print) 
 
 
 
 
 
 
 
 
 
                     
    __________  
Investigator’s Signature 
 
 
 
 
 
Date 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
5  
 
1. 
AMENDMENT RATIONALE 
Amendment 3 
The protocol dated 12 October 2018 was amended to update the medical monitor contact information, as 
well as provide an update to the stats section.  
Amendment 2 
Amendment 2 dated 12 Sep 2018 of the protocol A-101-WART-301 has been amended to include subjects ≥ 
1 years of age and to clarify the application procedures for younger subjects randomized to the study.  This 
change in inclusion criteria is at the request of the FDA following a review of the pediatric plan for this 
program. 
Amendment 1 
The protocol dated 09 July 2018 has been amended to change the patient instruction sheet, to provide 
updated information on how to return the used applicators to the site for final accountability.  The rationale 
for this change is to simplify the instructions provided for any product which may remain in the applicator 
after it is applied at home, by removing the need to express any remaining product and the need to use a 
sharps container for disposal.  The protocol was also amended to clarify that cantharidin has a 28 day wash 
out window prior to joining the study, and that the concomitant use of cantharidin is prohibited while on study.   
Lastly, the study title has been updated throughout the document to include the branded study name, 
THWART.    
1.1. 
Protocol Changes 
Protocol 
Version 
Date 
Section 
Revisions 
Version 
2.0 
09 July 
2018 
NA 
Original Protocol  
Version 
3.0 
10 
September 
2018 
 
 
 
 
Title 
THWART 1, the branded study name, has been added to 
the study title throughout the document. 
 
 
Synopsis 
Revised exclusion criteria number 7 to clarify the wash 
out period for cantharidin use prior to study entry. 
 
 
Section 8.2 
Revised exclusion criteria number 7 to clarify the wash 
out period for cantharidin use prior to study entry. 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
6  
 
Protocol 
Version 
Date 
Section 
Revisions 
 
 
Section 10.7 
Language added to instruct all subjects/guardians that 
nitrile examination gloves must be worn during the 
application of A-101 study medication 
 
 
Section 11.1 
Revised the previous therapy list to clarify the wash out 
period for cantharidin use prior to study entry. 
 
 
Section 11.3 
Revised the prohibited medication list to include 
cantharidin use while on study as prohibited. 
 
 
Section 12.5 
Added nitrile gloves to the list of clinical supplies. 
 
 
Appendix 1 
Revised the patient instruction sheet to simplify the 
disposal of the applicator at home.  Additionally, typos 
and formatting were updated to provide clarity.  
Version 4 
12 Oct 2018 Synopsis, Inclusion 
criteria #2, Section 
7.1, Table 2 
Footnote 14 and 15, 
Section 10.5 and 
Section 10.7 
The age range for eligibility was broadened to subjects ≥ 
1 years of age.  
 
 
Section 10.7, Table 
2 Footnote 14, 
Section 11.3, 
Section 12.4 and 
Appendix 1 
Added clarification that parents/guardians should 
ensure that children should not put a treated area in 
their mouth or eyes until the treated area is dry post-
application. If the area is not dry 10 minutes after the 
application, the parent is advised to blot the area dry. 
Version 5 
14 Feb 
2019 
Cover page 
The medical monitor information has been updated to 
the current medical monitor. 
 
 
Section 10.6 
The language was updated to reflect that unused study 
medication will be disposed of after final accountability. 
 
 
Section 15 
The stats section of the protocol has been updated to 
reflect the planned statistical analyses that will be 
performed. 


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Protocol Number:  A-101-WART-302 
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2. 
SYNOPSIS 
Protocol Number A-101-WART-302 Synopsis 
Protocol Number:  
A-101-WART 302 
THWART 2: 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 
Sponsor: 
Aclaris Therapeutics 
 
Phase of Development: 
Phase 3 
Study Drug Description: 
 
A-101 Solution contains 45% hydrogen peroxide that will be supplied in a single use applicator to be 
applied directly to common warts (verruca vulgaris) twice a week.     
 
The study drug, A-101 (hydrogen peroxide) 45% Topical Solution (hereafter referred to as A-101) is a 
colorless solution that must be stored at room temperature (15-25º C or 59 -77 º F).  The blinded 
vehicle solution is packaged to match the active study drug and will be stored under the same 
conditions.   
Study Objectives: 
 
Primary: 
The primary objective of this study is to evaluate the effectiveness of A-101 45% compared to Vehicle 
when applied twice weekly to common warts.  
 
Secondary: 
The secondary objectives of this study include: 
• 
Duration of response 
• 
Onset of action of A-101 45%.  
• 
Safety of A-101 45%. 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
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Study Design:   
This is a phase 3, multicenter, randomized vehicle controlled, double blind parallel group study to 
evaluate the safety and efficacy of A-101 45% vs Vehicle in subjects with common warts. Investigators 
will be required to identify at least 1 and up to 6 clearly identifiable common warts for treatment with 
A-101 study medication.  All identified common warts will be treated twice a week for up to 8 weeks 
(maximum of 16 treatment applications). Subjects will be followed for 12 weeks after Visit 9.         
 
Approximately 500 subjects will be randomized to one of 2 treatment arms in a 1:1 ratio.  Of the 500 
subjects randomized, approximately 100 subjects will be between 1 and 17years of age.  The duration 
of study participation is anticipated to be up to a maximum of 158 days per subject.   
 
Safety will be evaluated based on clinical laboratory studies (hematology and clinical chemistry), vital 
signs, assessment of local skin reactions (LSRs), assessment of adverse events (AEs), physical exams, 
and concomitant medication review.   
 
Efficacy will be evaluated based on assessment of each identified common wart according to the 
Physician Wart Assessment (PWA)scale.  The Investigator should NOT refer to any other assessments or 
previous assessments to assist with this evaluation.  
 
Sites will be required to take standardized color photographs to assist with the documentation of the 
appearance and location of each identified common wart throughout the study.  These photographs 
are not to be used when performing the PWA.   
 
Number of Patients to be Enrolled: 
 
Approximately 500 subjects will be randomized to the study.   
Number of Study Sites: 
 
This study will be conducted in the US only at approximately 25 treatment centers.   


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
9  
 
Inclusion Criteria: 
Subjects must meet all the following criteria to be considered for participation in this study.   
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 ≥ 1 year 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:   
a. Have a longest axis that is ≥3 and ≤8 mm and have a thickness of ≤3mm 
b. Be a discrete lesion, i.e. each wart meeting the entry criteria is clearly separated from 
other warts. 
c. Be present for at least 4 weeks 
d. Not be covered with hair which, in the investigator’s opinion, would interfere with 
the study medication treatment or the study evaluations 
e. Not be in an intertriginous fold 
f. 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: 
Subjects are excluded from this study if any of the following criteria is met: 
1. Subject has clinically atypical common warts. 
2. Subject is immunocompromised (e.g., due to chemotherapy, systemic steroids, genetic 
immunodeficiency, transplant status, etc.). 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
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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: 
• 
Immunotherapy (e.g., Candida antigen, mumps antigen, Trichophyton antigen); 8 
weeks 
• 
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: 
• 
Immunomodulatory/immunosuppressant therapy (e.g., etanercept, alefacept, 
infliximab); 16 weeks 
• 
Glucocortico-steroids (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: 
• 
LASER, light or other energy-based therapy (e.g., intense pulsed light [IPL], 
photodynamic therapy [PDT]); 180 days 
• 
Immunotherapy (e.g., imiquimod, squaric acid dibutyl ester[SADBE], etc.) 12 weeks 
• 
Liquid nitrogen, electrodesiccation, curettage; 60 days 
• 
Hydrogen peroxide; 90 days 
• 
Antimetabolite therapy (e.g., 5-fluorouracil); 8 weeks 
• 
Retinoids; 90 days 
• 
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 a 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: 
• 
Cutaneous malignancy; 180 days 
• 
Sunburn; currently 
• 
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 within 30 days prior to Visit 1.  


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
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12. Subject has an active malignancy. 
13. Subjects viewed by the Principal Investigator as not being able to complete the study.   
Duration of Treatment 
The duration of the study participation is anticipated to be a maximum of 157 days per subject.  The 
final visit (Visit 13) has a maximum allowable visit window of 7 days:  Study visits are: 
• 
Visit 1 (Day -13 to 0) screening 
• 
Visit 2 (Day 1) randomization; study medication treatment 
• 
Visit 3 (Day 8) study medication treatment  
• 
Visit 4 (Day 15) study medication treatment 
• 
Visit 5 (Day 22) study medication treatment 
• 
Visit 6 (Day 29) study medication treatment 
• 
Visit 7 (Day 36) study medication treatment 
• 
Visit 8 (Day 43) study medication treatment 
• 
Visit 9 (Day 50) study medication treatment 
• 
Visit 10 (Day 60) follow up evaluations, no identified Wart retreatment 
• 
Visit 11 (Day 78) follow up evaluations, no identified Wart retreatment 
• 
Visit 12 (Day 106) follow up evaluations, no identified Wart retreatment 
• 
Visit 13 (Day 137) follow up evaluations, no identified Wart retreatment; end of study 
Study Endpoints: 
Primary Efficacy Endpoint: 
The primary efficacy endpoint is the proportion of subjects whose identified common warts are 
determined to be clear on the PWA scale (PWA=0) at Visit 10 (Day 60). 
 
Secondary Efficacy Endpoint: 
The secondary efficacy endpoints are: 
• 
Proportion of subjects whose identified common warts are clear on the PWA scale (PWA =0) 
at Visit 13 (Day 137; last follow-up evaluation). 
• 
Mean per-subject percent of all warts that are clear on the PWA scale at Visit 13 (Day 137) 
• 
Proportion of subjects with a single wart at baseline whose wart is clear on the PWA scale 
(PWA=0) at Visit 10 (Day 60) 
• 
Median time for subjects to achieve clearance (PWA=0) of all treated common warts. 
 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
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Criteria for Evaluation 
Efficacy: 
The investigator will evaluate the severity of the identified Warts using the Physician Wart 
Assessment (PWA) scale. 
 
Safety: 
Safety will be evaluated by following adverse events, clinical laboratory exams, vital signs, 
concomitant medications, as well as through the assessment of local skin reactions, skin examinations 
and general physical exams.   
 
Study Drug Administration 
 
Study drug medication will be applied to each identified common wart which meets the requirements 
for retreatment twice a week for up to 8 weeks (maximum of 16 applications).   At Visit 2, subjects 
who are 18 years of age or older will apply the A-101 study medication in the presence of the treating 
physician or a member of the investigational site staff who is a trained healthcare professional.   The 
second weekly application of the A-101 study medication will be applied by the subject at home.  
Subjects between the ages of 1 and 17 years of age will have their A-101 study medication applied in 
the office by a parent or legal guardian in the presence of the treating physician or a member of the 
investigational site staff.  The second weekly A-101 study medication application will be applied at 
home by a parent or a legal guardian.     
 
Study medication must be applied to each identified common wart for approximately 15 seconds. The 
treated wart must remain undisturbed for an additional approximately 15 seconds.  This treatment 
cycle must be repeated up to 3 times to the common wart.   If severe erythema and edema develop, 
then the treatment cycle should be discontinued for that specific treatment application.    
 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES  
TABLE OF CONTENTS 
INVESTIGATOR’S AGREEMENT ...............................................................................................4 
1. 
AMENDMENT RATIONALE ....................................................................................5 
1.1. 
Protocol Changes ..........................................................................................................5 
2. 
SYNOPSIS ...................................................................................................................7 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............13 
TABLE OF CONTENTS ...............................................................................................................13 
LIST OF TABLES .........................................................................................................................17 
LIST OF FIGURES .......................................................................................................................18 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................19 
5. 
INTRODUCTION ......................................................................................................22 
5.1. 
Summary .....................................................................................................................22 
5.2. 
Study Rationale ...........................................................................................................24 
6. 
OBJECTIVES .............................................................................................................27 
6.1. 
Study Objectives .........................................................................................................27 
6.1.1. 
Primary Objective .......................................................................................................27 
6.1.2. 
Secondary Objectives .................................................................................................27 
7. 
STUDY DESIGN .......................................................................................................28 
7.1. 
Number of Subjects and Study Centers ......................................................................28 
7.2. 
Duration of Study .......................................................................................................28 
8. 
STUDY ENTRY CRITERIA .....................................................................................29 
8.1. 
Inclusion Criteria ........................................................................................................29 
8.2. 
Exclusion Criteria .......................................................................................................29 
8.3. 
Removal of Subjects from Study Therapy ..................................................................30 
8.4. 
Withdrawal Procedures ...............................................................................................31 
8.5. 
Subject Replacement ..................................................................................................31 
8.6. 
Subject Identifier (SI) .................................................................................................31 


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9. 
STUDY PROCEDURES ............................................................................................32 
10. 
STUDY TREATMENT ..............................................................................................37 
10.1. 
Investigational Study Medication ...............................................................................37 
10.2. 
Subject Randomization ...............................................................................................37 
10.3. 
Study medication packaging, storage, and dispensing ...............................................38 
10.4. 
Drug Accountability ...................................................................................................38 
10.5. 
Study Medication Treatment ......................................................................................38 
10.6. 
Preparing the Study Medication for Application ........................................................40 
10.7. 
Applying Study Medication ........................................................................................42 
10.8. 
Dose Modification ......................................................................................................43 
10.9. 
Breaking the Blind ......................................................................................................43 
11. 
PREVIOUS AND CONCOMITANT THERAPIES ..................................................44 
11.1. 
Previous Therapy ........................................................................................................44 
11.2. 
Concomitant Therapies ...............................................................................................44 
11.3. 
Prohibited Therapies ...................................................................................................45 
12. 
ASSESSEMENTS OF CLINICAL EFFICACY ........................................................46 
12.1. 
Common Wart Identification ......................................................................................46 
12.2. 
Standardized Photography ..........................................................................................47 
12.3. 
Physician’s Wart Assessment (PWA) ........................................................................48 
12.4. 
Subject Instructions ....................................................................................................48 
12.5. 
Parents/legal guardians of children must ensure that the child does not put the treated 
area in their mouth, or eyes, until completely dry after the application. If the treated area 
is not completely dry 10 minutes after the application, the area should be blotted 
dry.Other Study Supplies ............................................................................................49 
13. 
ASSESMENT OF SAFETY .......................................................................................50 
13.1. 
Local Skin Reactions (LSRs)......................................................................................50 
13.2. 
Vital Signs ..................................................................................................................52 
13.3. 
Clinical Laboratory Sampling.....................................................................................52 
13.4. 
Demographics and Medical History ...........................................................................53 


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14. 
ADVERSE EVENTS..................................................................................................55 
14.1. 
Definitions ..................................................................................................................55 
14.1.1. 
Adverse Events (AEs) .................................................................................................55 
14.1.2. 
Serious Adverse Events (SAEs) .................................................................................56 
14.1.3. 
Adverse Event Reporting Period ................................................................................56 
14.1.4. 
Severity .......................................................................................................................56 
14.1.5. 
Relationship to Study Medication ..............................................................................57 
14.2. 
Reporting Procedures ..................................................................................................57 
14.2.1. 
Procedures for Reporting Adverse Events ..................................................................57 
14.2.2. 
Procedure for Reporting Serious Adverse Events ......................................................57 
14.2.3. 
Withdrawal Due to an Adverse Event ........................................................................58 
15. 
STATISTICAL CONSIDERATIONS .......................................................................59 
15.1. 
Sample Size and Power Considerations .....................................................................59 
15.2. 
Analysis of Populations ..............................................................................................59 
15.3. 
Statistical Analysis of Efficacy ...................................................................................59 
 
The first sensitivity analysis for the primary endpoint will be an analysis based upon the 
PP population.  This analysis will use the same CMH model described for the primary 
analysis.  A second sensitivity analysis will be conducted for the primary endpoint using 
the same CMH model for the ITT population that includes the imputation of missing 
PWA data using a fully conditionally specified (FCS) regression-based Multiple 
Imputation (MI) procedure. To assess the impact of missing data imputation on the 
primary analysis results a tipping point analysis will be conducted.  This analysis will 
shift the treatment coefficient in the regression model used in the MI procedure to 
impose a worse mean maximum PWA for the A-101 45% arm and a better mean 
maximum PWA for the vehicle arm.  Details of this tipping point analysis will be 
specified in the SAP.  In addition, a model similar to the primary analysis model but 
stratified instead by Study Center will be performed as a sensitivity analysis including a 
Breslow-Day test to evaluate heterogeneity across sites.   .........................................60 
15.4. 
Statistical Analysis of Safety Data .............................................................................61 
15.5. 
Interim Analysis ..........................................................................................................61 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................62 
16.1. 
Protocol Amendments ................................................................................................62 


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Protocol Number:  A-101-WART-302 
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16.2. 
Protocol Violations .....................................................................................................62 
16.3. 
Training .......................................................................................................................62 
16.4. 
Monitoring ..................................................................................................................62 
16.5. 
Data Management .......................................................................................................63 
16.6. 
Quality Assurance .......................................................................................................63 
16.7. 
Record Retention ........................................................................................................63 
17. 
ETHICS AND GENERAL STUDY CONDUCT CONSIDERATIONS ...................65 
17.1. 
Institutional Review Board (IRB)/Ethics Committee (EC) ........................................65 
17.2. 
Ethical Conduct of the Study ......................................................................................66 
17.3. 
Regulatory Documents ...............................................................................................66 
17.4. 
Contractual Requirements ..........................................................................................66 
18. 
REFERENCES ...........................................................................................................67 
APPENDIX 1. A-101-WART-302 SUBJECT INSTRUCTION SHEET ..................................68 
APPENDIX 2. PWA SITE USER MANUAL ............................................................................72 
 


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Protocol Number:  A-101-WART-302 
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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................19 
Table 2: 
Study Procedures ........................................................................................................33 
Table 3: 
Study Medication Information ....................................................................................37 
Table 4: 
Fitzpatrick Skin Type Scoring System .......................................................................54 
 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
Amendment 3: Version 5 14 February 2019 
 
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LIST OF FIGURES 
Figure 1: 
Diagram Showing the Process for Preparing A-101 Study Medication .....................41 
 
  


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Protocol Number:  A-101-WART-302 
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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms  
Abbreviation  
Term 
AE  
Adverse Event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BUN 
Blood Urea Nitrogen 
°C 
Degrees Celcius 
CBC 
Complete Blood Count 
CDMS 
Clinical Data Management System 
CMH 
Cochran-Mantel-Haenszel 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
e.g.  
for example, (Latin; exempla gratia) 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
eCRF 
Electronic Case Report Form 
°F 
Degrees Fahrenheit 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIV 
Human Immunodeficiency Virus 
HPV 
Human Papilloma Virus 


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Protocol Number:  A-101-WART-302 
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Abbreviation  
Term 
H2O2 
Hydrogen Peroxide 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization  
ID 
Identification 
i.e.  
that is (Latin; id est) 
IPL 
Intense Pulsed Light 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
LDH 
Lactate Dehydrogenase 
LSR 
Local Skin Reactions 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
Milliliter 
Mm 
Millimeter 
NCS 
Not Clinically Significant 
OTC 
Over-The-Counter 
PDL 
Pulsed-dye Laser 
PDT 
Photodynamic Therapy 
PWA 
Physician Wart Assessment 
SADBE 
Squaric Acid Dibutyl Ester 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SI 
Subject Identifier 
SOP 
Standard Operating Procedure 


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Protocol Number:  A-101-WART-302 
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Abbreviation  
Term 
US 
United States 
w/w 
Weight-to-weight 
 


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5. 
INTRODUCTION 
5.1. 
Summary 
Warts are benign proliferations of the skin and mucosa that are caused by infection of keratinocytes by 
subtypes of the human papilloma virus (HPV) family.  Cutaneous HPV subtypes are a subset of this large 
group of the DNA papillomavirus family that is capable of infecting humans and causing cutaneous lesions. 
HPVs are ubiquitous in the environment and infection occurs most commonly through direct contact with 
individuals who harbor the virus clinically (evident lesions) or sub-clinically, indirectly through exposure to 
contaminated surfaces, or even by autoinoculation of virus from individual lesions to adjacent uninfected 
skin. Cutaneous manifestations of HPV infection include common warts (verruca vulgaris), palmar and 
plantar warts, mosaic warts, flat warts, and butcher’s warts. Common warts are generally small, rounded, 
hyperkeratotic, exophytic dome-shaped papules or nodules and are typically associated with HPV subtypes 
1, 2 or 4 though other subtypes are reported. Lesions are most commonly located on the fingers (including 
periungual and subungual regions), dorsal surfaces of the hands, and sites prone to trauma (e.g., knees, 
elbows), but commonly occur at virtually any other anatomical location, potentially spreading by 
autoinoculation from the finger/hand lesions. 
In immunocompetent individuals, many common cutaneous warts (up to 2/3rds in some reports) may 
spontaneously resolve in less than 2 years. However, they often persist for many years, may be large and/or 
cosmetically unsightly (e.g., face, hands), spread to distant anatomical regions by autoinoculation, be painful 
and/or prone to trauma, and, importantly, provide a significant reservoir of HPV infection in the community, 
placing (especially immunocompromised) individuals at risk for significant morbidity. 
There are currently no specific antiviral therapies available to treat cutaneous HPV infection and there is no 
FDA-approved topical treatment for cutaneous common warts. Existing therapies, many of which are off-
label uses of drugs approved for other indications, and many of which have never undergone the drug 
approval process, are  of unproven safety and/or efficacy, and are generally directed towards either the direct 
physical destruction of the lesions with locally destructive or ablative modalities such as cryotherapy, 
electrosurgery, curettage, application of acids (e.g., salicylic acid, trichloroacetic acid); locally cytotoxic 
therapies, such as topical podophyllin, cantharidin, topical or intralesional 5-fluorouracil, or bleomycin; 
topical immunomodulatory or immunotherapy (e.g., topical imiquimod, intralesional candida antigen, 
topical squaric acid dibutyl ester) or lesion removal. Several of these therapies are also available as over-the-
counter (OTC) wart therapies in lesser exposures than used in the office setting (e.g., topical salicylic acid 
preparations, home freezing kits). Systemic therapy with agents such as cimetidine, and even local occlusion 
with duct tape have also been anecdotally reported to be effective in some cases. While these methods may 
achieve cure in some cases, many require multiple visits to a physician’s office, and may require providers 
with specialized training and the use of expensive equipment. Such procedures can be painful, may require 
anesthesia and/or analgesia, and they can be complicated by adverse cosmetic outcomes including scarring 
at the treatment site, as well as the typical post-surgical risks of bleeding and infection. No one therapy is 


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Protocol Number:  A-101-WART-302 
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consistently effective in all cases and, in fact, there is great variability among practitioners in the methods 
employed using each of these techniques with great variability of the results. 
Hydrogen peroxide (H2O2) is a compound that is ubiquitous in the environment. It is the simplest peroxide 
and a potent oxidizing agent commonly used in innumerable household goods including chlorine-free 
bleaches, general-purpose cleaning products, and disinfectants. Additionally, H2O2 has been employed as the 
oxidizing component in hair dyes, and has been used in oral hygiene products and tooth-whitening systems 
for many years. In industry, it is employed in the treatment of wastewater. In high concentrations, it is used 
in bleaching paper, pulp, and textiles. Clinically, in addition to its use as an oral topical agent noted above, 
H2O2 is widely employed at low concentrations (e.g., 3%-6%) as a wound irrigant and topical 
antiseptic/disinfectant, and has been in use medicinally since its introduction into clinical practice by 
Richardson in 1858.  (Schumb, 1955) (Chan, 2008) (Richardson, 1866) (Richardson, 1891) (Watt, 2004) 
(Zonios, 2007). 
H2O2 is an important oxidizing agent in biological systems. The local deleterious effects of reactive oxygen 
species on the skin are mitigated by the presence of a complex antioxidant defense system that includes, 
enzymes such as catalase, glutathione peroxidase, superoxide dismutase, thioredoxin reductase, lipoamine, 
lipid peroxidase and others, as well as non-enzymatic components including ascorbic acid, urates and uric 
acid, tocopherol, glutathione, ubiquinones, ubiquinol and other water-soluble groups.  The local application 
of supra-physiologic concentrations of H2O2 may overwhelm the antioxidant defense systems in the skin, 
allowing H2O2 to act not only through its direct oxidation of organic tissues, generation of reactive oxygen 
species, and local lipid peroxidation, but also by the generation of local concentrations of O2 that are toxic to 
the abnormal lesional (seborrheic keratosis) cells. 
 
An investigator-initiated, single-site, double-blind, vehicle-controlled, parallel-group proof-of-concept trial: 
“A randomized, double-blind, vehicle-controlled, parallel group study of hydrogen peroxide solution in 
adult subjects with common warts of the hand (WART-01), was conducted utilizing once weekly 
applications (maximum of four applications) of A-101 (hydrogen peroxide) 40% topical solution or placebo 
(vehicle) topical solution to investigate the potential utility of a 40% hydrogen peroxide topical solution for 
the treatment of common warts on the hands. A total of 15 subjects received 4 study medication 
applications. One subject achieved complete clearance of the Target Wart during the investigation, and data 
from this pilot study demonstrated a statistically significant trend towards clearing warts in the A-101 40% 
group when compared with the vehicle. It was the Investigator’s opinion that “1 or 2 additional treatments 
may clear the warts as most A-101 40% treated warts were “Near Clear” at the end of the four-week study”. 
The administration of A-101 40% over four applications one week apart showed no untoward effects and the 
treatment was well tolerated by all subjects. The data and clinical observations suggest that a larger study 
allowing greater than four drug applications and evaluating additional doses of A-101 topical solution are 
warranted. 


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5.2. 
Study Rationale 
Aclaris has conducted three (3) Phase 2 studies to determine the dose response and dose frequency of 
A-101 (H2O2) Topical Solution in patients with common warts. The three studies conducted are 
identified below and they represent data collected from 406 subjects. 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-302 
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• 
Study A-101-WART-201: A Randomized, Double-Blind, Vehicle-Controlled, Parallel- 
Group, Study of A-101 Solution in Subjects with Common Warts (n=90). 
• 
Study A-101-WART-202: A Randomized, Double-Blind, Vehicle-Controlled, Parallel 
Group Study of A-101 Topical Solution Applied Once a Week in Subjects with Common 
Warts (n=157). 
• 
Study A-101-WART-203: A Randomized, Double-Blind, Vehicle-Controlled, Parallel 
Group Study of A-101 Topical Solution Applied Twice a Week in Subjects with 
Common Warts (n=159). 
 
The results from Study A-101-WART-201 evaluated two concentrations of A-101 (H2O2) 
Topical Solution: 40% and 45% (w/w) compared with vehicle. The 45% (w/w) concentrations 
demonstrated clinically and statistically significant results in clearing warts while the 40% 
concentration had no effect when compared with vehicle. Therefore, A-101 40% topical 
solution was judged to be an ineffective concentration and not evaluated in further Phase 2 
studies. 
 
The results from Study A-101-WART-202, which evaluated a 45% (w/w) concentration of A-
101 (H2O2) Topical Solution when treating a single target wart and up to 3 additional warts 
showed that the 45% concentration applied once weekly resulted in a clinically and 
statistically significant clearing of warts at the end of the treatment period (Day 56) and at the 
end of a 12-week post-treatment follow-up (Day 134). 
 
The results from Study A-101-WART-203, which evaluated a 45% concentration of A-101 
(H2O2) Topical Solution administered twice weekly to a single target wart and up to 5 
additional warts showed that the 45% (w/w) concentrations resulted in clinically and 
statistically significant clearing of the target wart and all treated warts at the end of the 
treatment period (Day 56) and at the end of a 12-week, post-treatment follow-up (Day 134). 
The results from Study WART-203 were clinically and statistically significant clearance of warts 
at the end of the treatment period (Day 56) and at the end of a 12-week post-treatment 
follow-up (Day 134), with consistently earlier and stronger results than the data from Study 
WART-202 which incorporated a once weekly dose regimen. 
 
A-101 (H2O2) 45% (w/w) Topical Solution administered once weekly and twice weekly was well 
tolerated. Treatment emergent adverse events were predominantly mild and unrelated to 
study medication.  Local Skin Reactions (LSRs) were predominantly mild and transient. The 
LSRs of pruritus and stinging reported by subjects, and crusting, edema, erythema, and scaling 
reported by the investigator following treatment generally resolved by Visit 13 (Day 134). 
There were no clinically significant changes during the study in laboratory evaluations or vital 
signs. 


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6. 
OBJECTIVES 
6.1. 
Study Objectives 
6.1.1. 
Primary Objective 
The primary objective of this study is to evaluate the effectiveness of A-101 45% compared to 
Vehicle when applied twice weekly to common warts. 
6.1.2. 
Secondary Objectives 
The secondary objectives of this study include: 
• 
Duration of response to A-101 45% compared to Vehicle. 
• 
Onset of action of A-101 45% compared to Vehicle. 
• 
Safety of A-101 45%. 


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7. 
STUDY DESIGN 
This is a phase 3, multicenter, randomized, vehicle controlled, double blind parallel group study 
designed to evaluate the efficacy and safety of A-101 45% compared to Vehicle in subjects with 
common warts. 
During the study, the investigator will identify at least 1 and up to 6 common warts to be treated 
twice a week for up to 8 weeks (maximum of 16 treatment applications) 
Subjects will be required to complete a total of 13 study visits.  The protocol defined study visits are: 
• 
Visit 1 (Day -13 to 0) screening 
• 
Visit 2 (Day 1)* randomization; study medication treatment 
• 
Visit 3 (Day 8)* study medication treatment  
• 
Visit 4 (Day 15)* study medication treatment 
• 
Visit 5 (Day 22)* study medication treatment 
• 
Visit 6 (Day 29)* study medication treatment 
• 
Visit 7 (Day 36)* study medication treatment 
• 
Visit 8 (Day 43)* study medication treatment 
• 
Visit 9 (Day 50)* study medication treatment 
• 
Visit 10 (Day 60) follow up evaluations, no identified Wart retreatment 
• 
Visit 11 (Day 78) follow up evaluations, no identified Wart retreatment 
• 
Visit 12 (Day 106) follow up evaluations, no identified Wart retreatment 
• 
Visit 13 (Day 137) follow up evaluations, no identified Wart retreatment; end of study 
*The second weekly application will be applied by the subject/parent/legal guardian at home 
(Day 4, 11, 18, 25, 32, 39, 46, and 53). 
Refer to Table 2 for a complete list of protocol required study assessments. 
7.1. 
Number of Subjects and Study Centers 
Approximately 500 subjects will be randomized to one of two treatment arms at approximately 
25 investigational centers in the US.  Of the 500 subjects randomized, approximately 100 
subjects will be between 1 and 17 years of age. 
7.2. 
Duration of Study 
The anticipated time for study enrollment is approximately 3 months. The duration of study 
participation is anticipated to be a maximum of 157 days per subject. Subjects will have a total of 
13 study visits.  The maximum anticipated duration for the study is approximately 10 months. 


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8. 
STUDY ENTRY CRITERIA 
8.1. 
Inclusion Criteria 
Subjects must meet all the following criteria to be considered for participation in this study.   
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 ≥ 1 year 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:   
a. Have a longest axis that is ≥3 and ≤8 mm and have a thickness of ≤3mm 
b. Be a discrete lesion, i.e. each wart meeting the entry criteria is clearly separated from 
other warts. 
c. Be present for at least 4 weeks 
d. Not be covered with hair which, in the investigator’s opinion, would interfere with the 
study medication treatment or the study evaluations 
e. Not be in an intertriginous fold 
f. 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.   
8.2. 
Exclusion Criteria 
Subjects are excluded from this study if any of the following criteria is met: 
1. Subject has clinically atypical 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: 
• 
Immunotherapy (e.g., Candida antigen, mumps antigen, Trichophyton antigen); 8 weeks 
• 
Anti-metabolite therapy (e.g., bleomycin, 5-fluorouracil); 8 weeks 


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6. Subject has used any of the following systemic therapies within the specified period prior to 
Visit 2: 
• 
Immunomodulatory/immunosuppressant therapy (e.g., etanercept, alefacept, 
infliximab); 16 weeks 
• 
Glucocortico-steroids (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: 
• 
LASER, light or other energy-based therapy (e.g., intense pulsed light [IPL], 
photodynamic therapy [PDT]); 180 days 
• 
Immunotherapy (e.g., imiquimod, squaric acid dibutyl ester[SADBE], etc.) 12 weeks 
• 
Liquid nitrogen, electrodesiccation, curettage; 60 days 
• 
Hydrogen peroxide; 90 days 
• 
Antimetabolite therapy (e.g., 5-fluorouracil); 8 weeks 
• 
Retinoids; 90 days 
• 
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: 
• 
Cutaneous malignancy; 180 days 
• 
Sunburn; currently 
• 
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.   
8.3. 
Removal of Subjects from Study Therapy 
A subject may be removed from the study therapy for a variety of reasons, including: 
• 
Unacceptable adverse event 
• 
Subject unwilling or refusal to continue with the protocol defined study visits and/or consent 
withdrawal for study participation 
• 
Change in compliance with an inclusion/exclusion criteria 
• 
Use of a prohibited medication (through Visit 13) 
• 
General or specific changes in the subject’s condition that render the subject unacceptable for 
further treatment in this study in the judgement of the investigator. 


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If a subject is to be withdrawn from the study, the Aclaris Therapeutics, Inc. CRA or designee must be 
informed within 24 hours of the decision to remove the subject from the study.   
 
The study may be discontinued at the discretion of Aclaris Therapeutics, Inc.  Some examples of reasons 
for discontinuation are the occurrence of the following:   
• 
Increased frequency, severity or duration of known AEs 
• 
Medical, regulatory or ethical reasons affecting the continued performance of the study 
• 
Difficulties in the recruitment of subjects 
8.4. 
Withdrawal Procedures 
If a subject withdraws from the study prior to Visit 13, the reason for and the date of withdrawal 
from the study must be recorded on the eCRF.  If the reason for withdrawal is an adverse event 
or a clinically significant abnormal laboratory test result, monitoring of the subject will continue 
until the event has resolved or stabilized, until the patient is referred to the care of a local health 
care professional, or until a determination of a cause unrelated to the study drug or study 
procedure is made. 
8.5. 
Subject Replacement 
Subjects that are determined to be screen failures may be rescreened for the study and if 
determined to be eligible for the study they may be randomized using the same subject identifier.  
A screen failure is a subject that signs an informed consent form for participation in the study but 
is determined not to be eligible for the study prior to the subject being randomized to the study.   
8.6. 
Subject Identifier (SI) 
The investigator or designee will assign a unique five-digit subject identifier (SI) to each subject 
at Visit 1. 
The SI format will be NN-NNN where the first 2 digits are the investigational center site number 
(using leading zeroes, as appropriate). The final 3 digits are the subject number and must be 
assigned in ascending numerical order, without omitting or repeating any number, starting with 
001 at each investigational center. For example, the SI for the second subject that signs an 
informed consent at site number 04 would be 04-002. 
The subject will be identified using the SI in all study documentation for the duration of the 
study. 
 


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9. 
STUDY PROCEDURES 
The schedule of study activities (including assessments, tests, exams, disease assessments, and 
study drug administration) beginning with screening and continuing through the end of study are 
outlined in Table 2 .  A written, signed informed consent form (ICF) must be obtained from each 
subject prior to performing any study related procedure (e.g., vital signs, clinical laboratory 
sampling, or photography). 


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Table 2: 
Study Procedures 
Visit  
V1 
Screening 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
 
V9 
V10 
V11 
V12 
V13 
Treatment Day 
-13 to 0 
1 
8 
15 
22 
29 
36 
43 
50 
60 
78 
106 
137 
 Treatment Window 
N/A 
N/A 
±1 
day 
±1 day 
±1 day 
±1 day 
±1 day 
±1 day  
±1 day 
+4 days 
±7 
days 
±7 
days 
+7 days 
Study Procedures 
 
Informed Consent 
▲ 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion Criteria/Exclusion 
Criteria 
▲ 
▲1 
 
 
 
 
 
 
 
 
 
 
 
Subject Identifier 
▲2 
 
 
 
 
 
 
 
 
 
 
 
 
Medical 
history/demographics 
▲ 
 
 
 
 
 
 
 
 
 
 
 
 
Fitzpatrick Skin Type 
Assessment 
▲3 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs 
▲4 
 
 
 
 
 
 
 
▲ 
 
 
 
▲ 
Prior 
Medications/Therapies 
▲5 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Chemistry and CBC6 
▲ 
 
 
 
 
 
 
 
 
 
 
 
▲ 
Common Wart 
Identification7 
▲ 
 
 
 
 
 
 
 
 
 
 
 
 
Physician’s Wart 
Assessment8 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 


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Visit  
V1 
Screening 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
 
V9 
V10 
V11 
V12 
V13 
Treatment Day 
-13 to 0 
1 
8 
15 
22 
29 
36 
43 
50 
60 
78 
106 
137 
 Treatment Window 
N/A 
N/A 
±1 
day 
±1 day 
±1 day 
±1 day 
±1 day 
±1 day  
±1 day 
+4 days 
±7 
days 
±7 
days 
+7 days 
Common Wart 
Dimensions9 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Standardized 
Photography10 
▲ 
▲11 
 
▲ 
 
▲ 
 
 
▲ 
▲ 
▲ 
▲ 
▲ 
Subject Randomization 
 
▲12 
 
 
 
 
 
 
 
 
 
 
 
Local Skin Reactions 
 
▲13 
▲13 
▲13 
▲13 
▲13 
▲13 
▲13 
▲ 
▲ 
▲ 
▲ 
▲ 
Study Medication 
Application14 
 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
 
 
 
 
Study Medication 
Application at Home15 
 
 
A-101 Study Medication will be applied at home on Days 4, 11, 
18, 25, 32, 39, 46, 53.  A window of +1 day is allowed.  
 
 
 
 
Subject Instructions 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
 
Concomitant therapies16 
 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
 
Adverse Events17 
 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
 
 
1Subject inclusion/exclusion criteria will be re-assessed prior to randomization during Visit 2.  
2Investigational sites will assign a unique five-digit subject identifier to each subject at Visit 1. This subject identifier will be used in all study documentation for 
the duration of the study.   
3Each subject’s skin must be assessed during Visit 1 using the Fitzpatrick Skin Type Assessment.   


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4Vital signs [including temperature, pulse, respiratory rate, blood pressure, height and weight (Visit 1 only)] will be measured by a qualified staff member at 
Visit 1, Visit 9 and Visit 13.   
5Prior medications/therapies will be collected for a time-period of 14 days prior to Visit 2.  Refer to Section 11 for a list of permitted and restricted concomitant 
medications.    
6A complete blood count (including hematocrit, hemoglobin, platelet count, red blood cell count and morphology, white blood cell count and differential 
(absolute and %) including basophils, eosinophils, lymphocytes, monocytes and neutrophils and a clinical chemistry panel including albumin, alkaline 
phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), bicarbonate, calcium, chloride, creatinine, glucose, 
lactate dehydrogenase (LDH), phosphorus, potassium, sodium, total bilirubin, total protein, and uric acid.   
7The treating investigator will identify at least 1 and up to 6 common warts located on the trunk or extremities that meet the inclusion criteria outlined in 
Section 7.   
8 The investigator will use the Physician Wart Assessment (PWA) scale to assess each identified common wart.  The investigator must assess the identified 
common warts prior to application of the study medication at Visit 2-Visit 9.  In order to be eligible for randomization at Visit 2, each common wart must have a 
PWA grade ≥ 2.   
9 The investigator will measure the dimensions (longest axis and thickness of the common wart) at Visit 1 and prior to randomization at Visit 2.  In order for the 
subject to be randomized at Visit 2 the identified common warts must have the specific dimensions outlined in Section 12.1.   The investigator will be required 
to measure the longest axis of each common wart at Visits 2-13. 
10 At Visits 1, Visit 2, 4, 6, and 9 (prior to study medication application), and Visit 10-13, a qualified investigational center staff member will take a photograph 
of each identified common wart using the Aclaris supplied camera.  All photographs will be sent to a central imaging laboratory.   
11At a sub-set of investigational sites (up to 3 sites), subjects randomized at these sites will have additional standardized photographs taken of their common 
warts at the following time-points:  V2-10 minutes post application, 1-hour post application and 24 hours post application.    
12Subjects will be randomized at Visit 2 prior to application of study medication.  Investigational study staff will re-confirm subject eligibility prior to 
randomization.   
13 The investigator and subject will assess each identified common wart for local skin reactions associated with irritation at Visits 2-13.  At Visit 2-Visit 9, the 
investigator and subject will assess each identified common wart for LSRs prior to the application of the study medication.  Refer to Section 13.1 for the 
complete list of Local Skin Reaction signs and symptoms. 
14 During in-office visits, subjects 18 years of age and older will apply their A-101 study medication in the presence of the treating physician or a member of the 
investigational study staff that has been trained on the protocol.  Subjects ages 1 to 17 will have their A-101 study medication applied by a parent/legal 
guardian in front of the treating physician or a member of the investigational study staff during in-office visits.  If the identified common wart meets the criteria 


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for re-treatment as defined in Section 10.6  the lesion will be re-treated at Visits 3-9.  Following application of study medication, subjects must NOT 
wash/submerge the treated wart for at least 6 hours and they must NOT apply any topical products to the treated common warts for at least 6 hours.  
Parents/legal guardians of children must ensure that the child does not put the treated area in their mouth, or eyes, until completely dry after the application. 
If the treated area is not completely dry 10 minutes after the application, the area should be blotted dry.15All subjects will receive their second weekly 
treatment of the A-101 study medication at home on Days 4, 11, 18, 25, 25, 32, 39, 46, 53 as determined by the PWA assessment performed during the in-
office visit.  Subjects ages 1 to 17 will have their A-101 study medication applied by a parent or legal guardian.  All subjects will need to document the 
application of A-101 study medication in a subject diary.  The second weekly treatment will depend on the PWA performed during the in-office visit that week.  
If the identified common wart meets the criteria for re-treatment during the in-office visit, then the subject/parent/guardian will perform the second weekly 
treatment at home.   
16All concomitant therapies including (topical and oral) prescription medications, over the counter medications and natural supplements and non-drug 
therapies including chiropractic, physical therapy, and energy-based therapy must be documented in the subject CRF.  Subjects must not apply any topical 
products (e.g., moisturizers, sunscreen, etc.) to the identified common wart within 12 hours prior to any study visit.   
17The reporting period for Serious Adverse Events (SAEs) begins when the subject signs the informed consent and continues through Visit 11.  Refer to Section 
Section 14.1.2  for instructions on the reporting of SAEs.  Non-serious clinical adverse events will be collected following the application of the study medication 
at Visit 2 and through Visit 11. Non-serious adverse events that occur between the time of consent and study medication application will be documented as 
medical history.   All safety reporting (AEs and SAEs) will conclude at Visit 11 (approximately 28 days after last study medication application) except for 
clinical adverse events related to local skin reactions.   
  
 


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10. 
STUDY TREATMENT 
10.1. 
Investigational Study Medication 
The study medications for the study are A-101 45%, and matching Vehicle.  All study 
medications are clear, colorless solutions which are indistinguishable in physical appearance. 
Table 3: 
Study Medication Information 
Study Medication 
Name 
A-101 45% 
Vehicle 
Manufacturer 
James Alexander Corporation, Blairstown NJ 
A-101 concentration 
(%) 
45 
0 
Pharmaceutical Form 
Solution 
Storage Conditions 
59ºF to 77ºF (15ºC to 25ºC) excessive heat, open flame and 
combustibles, out of direct sunlight and in a well-ventilated, dry area 
Route 
Topical 
Frequency 
A-101 Study Medication will be applied twice a week for 8 weeks.   
Duration of 
Administration 
Apply study medication to each identified common wart for 
approximately 15 seconds.  Allow each treated wart to remain 
undisturbed for approximately 15 seconds.  Repeat the 
application/waiting cycle until the study medication has been applied 
to each identified common wart up to 3 times.   
Activated Applicators 
Activated applicators are stable for 4 hours at room temperature (59ºF 
to 77ºF or 15ºC to 25ºC) 
 
10.2. 
Subject Randomization 
Prior to the start of the study, Aclaris Therapeutics, Inc./designee will generate a randomization list that 
will be provided to the assigned clinical packaging organization for study medication labeling.   
 
The randomization list will be stored with limited access to designated personnel for study medication 
labeling.      
 


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Subjects will be randomized to the study in a 1:1 ratio and stratified by investigational study site.   Sites 
will be shipped study medication in blocks of 4.  Once a subject is determined to have met all inclusion 
criteria and does not meet any of the exclusion criteria, the site will pull the next sequential drug kit 
from their supply and enter the drug kit number into the EDC system.     
  
10.3. 
Study medication packaging, storage, and dispensing 
A-101 45% and matching Vehicle will be provided by Aclaris Therapeutics, Inc. and labeled 
according to applicable regulatory requirements.   
The study medication will be packaged in single use applicators.  The ampoule is provided inside 
a sealed polyethylene tube with a flocked, doe foot applicator on one end. 
Subject kits will contain 20 study medication applicators.  The blinded subject kits will remain at 
the investigational site and the site staff will dispense a study medication applicator to the subject 
for the at home treatment visit.    The outside of each subject kit and each individual treatment 
applicator will be labelled in compliance with applicable regulatory requirements.  
A-101 study medication must be stored in a location where there is limited access at 59ºF to 77ºF 
(15ºC to 25ºC) protected from excessive heat, open flame and combustibles, out of direct 
sunlight and in a well-ventilated, dry area.  Proper storage of the A-101 study medication must 
be reviewed with the subject prior to dispensing the blinded subject kit. 
Investigational study medication supplies are only to be used for subjects properly consented and 
randomized to this study. 
10.4. 
Drug Accountability 
The investigator or designee will maintain an accurate record of the receipt of the study 
medications as shipped by Aclaris Therapeutics, Inc. (or designee), including the date received 
and the condition of the study medications. One copy of this receipt will be returned to Aclaris 
Therapeutics, Inc. (or designee) when the contents of the study medication shipment have been 
verified and one copy maintained in the study file. In addition, an accurate study medication 
disposition record will be kept, specifying the amount dispensed for each subject and the date of 
dispensing. This inventory record will be available for inspection at any time. At the completion 
of the study, the original inventory record will be available for review by Aclaris Therapeutics, 
Inc. upon request. 
Final drug accountability will be completed by the CRA at the completion of the study and all 
unused study medication will be returned to Aclaris Therapeutics, Inc. drug depot for disposal 
per Aclaris Therapeutics, Inc. (or designee’s) written instructions. 
10.5. 
Study Medication Treatment 
The study medications are for external, topical use only and are to be applied only to those 
subjects that have been properly consented and randomized to the study. 


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The investigational center staff member must comply with the study medication storage 
conditions outlined in Section 10.1  
During Visit 2-Visit 9 (if the identified common wart meets the criteria for retreatment), the 
investigational study staff will select the appropriate study medication applicator for treatment of 
a specific subject. Subjects ages 18 years of age and older will apply the appropriately labeled A-
101 study medication to the identified common wart in the presence of the treating investigator 
or investigational staff that has been trained on the protocol.   The second weekly application of 
the A-101 study medication will be applied by the subject at home (Days 4, 11, 18, 25, 32, 39, 
46, and 53).  The second weekly treatment will be determined by the PWA assessment 
performed during the in-office visit. If the identified common wart meets the criteria for 
retreatment, then the subject will apply the A-101 study medication at home. 
Subjects between the ages of 1 and 17 years of age will have their A-101 study medication 
applied in the office by a parent or legal guardian in the presence of the treating physician or a 
member of the investigational site staff during Visit 2-Visit 9.  The second weekly A-101 study 
medication application will be applied at home by a parent or a legal guardian (Days 4, 11, 18, 
25, 32, 39, 46, and 53).  The second weekly treatment will be determined by the PWA 
assessment performed during the in-office visit. If the wart meets the criteria for retreatment, 
then the subject will apply the A-101 study medication at home. 
Retreatment Criteria: 
 
At Visit 3-9, if the identified common wart has a PWA grade of >0 then the subject will receive re-
treatment with the A-101 study medication treatment.  However, treatment with the A-101 study 
medication should not be applied if any of the following criteria apply to the identified common wart: 
• 
The common wart has a pre-treatment LSR grade of 3 (severe) for any sign or symptom AND 
the grade has increased compared to the previous visit. 
• 
The common wart is, in the investigator’s opinion, not appropriate for a retreatment (the 
investigator must note the reason on the subject’s Comments CRF page). 
• 
The common wart, in the Investigator’s opinion, cannot be visualized so the Investigator cannot 
assess the PWA. 
 
If the identified common wart meets the criteria for re-treatment during the in-office visit (PWA>0), 
then the subject/parent/legal guardian should treat the common wart at home on the protocol defined 
at home treatment days (Days 4, 11, 18, 25, 32, 39, 46, 53.  A window of +1 day is allowed).  If the 
subject is unable to tolerate treatment the day of an at home treatment visit due to severe skin 
irritation, then the treatment should be held and the investigational site should be notified.    
 


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Subjects whose identified common wart(s) is assessed at a particular visit (V3-V9) to be a PWA=0 will not 
have the that common wart re-treated at that visit (or retreated at the second at home application that 
week).   
10.6. 
Preparing the Study Medication for Application 
To perform a study medication treatment for the identified common wart a staff member will 
select the appropriate study medication applicator from the identified subject’s kit. The following 
instructions outline the procedure for application of the study medication to the identified 
common wart.  During each in-office treatment visit, the Investigational Study Staff will be 
responsible for reviewing the following instructions with the subject/parent/legal guardian and 
ensure that they understand how to properly prepare the applicator and apply the A-101 study 
medication. 
• 
For the in-office treatment applications, the Investigational Study Staff member will prepare the 
A-101 study medication applicator for all subjects, regardless of age by: 
o Washing their hands prior to, and after completing the study medication treatments  
o Wear nitrile or vinyl examination gloves during the treatment; latex gloves are 
prohibited 
o Visually inspect the applicator for damage: 
 
If the applicator appears damaged do not use it for the treatment, contact the 
study monitor for disposal instructions and select an unused applicator with the 
next highest number for the treatment 
If the applicator is intact, proceed with the applicator preparation process as outlined in Figure 1.  


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Figure 1: 
Diagram Showing the Process for Preparing A-101 Study Medication  
 
1. Each common wart should be cleaned using an alcohol wipe prior to application of A-101 
45%. 
2. Hold the applicator so that the applicator cap is pointing up. 
3. Crush the ampule in the applicator by applying pressure to the center of the barrel of the 
applicator. 
4. Remove the sleeve. 
5. Tap the barrel of the applicator to ensure the solution is free of the crushed ampule. 
6. Gently remove the cap by twisting while pulling away from the applicator. 
7. Express a single drop of A-101 45% so that the tip of the applicator becomes wet. 
8. Apply the solution to the identified warts in a circular motion. 
 
All subjects will be supplied with treatment application instruction sheets at the completion of 
each in-office visit. 


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10.7. 
Applying Study Medication   
All subjects that are between the ages of 1 and 17 will have their A-101 study medication applied by a 
parent/legal guardian. Parents/legal guardians of children must ensure that the child does not put the 
treated area in their mouth, or eyes, until completely dry after the application. If the treated area is not 
completely dry 10 minutes after the application, the area should be blotted dry. For in-office visits, the 
subject’s parent or legal guardian will apply the A-101 study medication in front of a member of the 
investigational study staff to ensure there is a clear understanding regarding how the study medication 
should be handled.   
 
Subjects 18 years of age and older will apply their A-101 study medication to his/her identified common 
warts in the presence of the treating physician or member of the investigational staff during in-office 
visits.  The second weekly application will be performed at home.   
 
The following instructions will be used by all subjects/parents/legal guardians applying A-101 study 
medication to all identified common warts:    
• 
Do not apply the study medications to eyes, nose, mouth, mucous membranes, or open wounds 
• 
Wear nitrile or vinyl examination gloves during the treatment; latex gloves are prohibited (All 
subjects will be supplied with nitrile or vinyl examination gloves to be used for at home 
applications) 
• 
Thoroughly cleanse the common wart by firmly rubbing with a swab/wipe wetted with 70% 
isopropyl alcohol 
• 
Using firm pressure and with the tip of the applicator held over the wart, squeeze in the middle 
of the applicator to apply one drop of study medication onto the common wart.  Using the 
smaller side of the applicator tip, move the applicator around in a circular motion to fully 
saturate the lesion.  Apply the study medication for approximately 15 seconds.   
• 
Minimize exposure to the surrounding normal skin 
• 
During the treatment process remove excess study medication from the surrounding skin using 
a clean absorbent wipe. 
• 
Ensure the identified common wart is fully saturated with study medication at the end of the 
~15 second application 
• 
Allow the treated wart to remain undisturbed for ~15 seconds 
• 
After ~15 seconds repeat the ~15 second application process 
• 
Repeat the application/waiting cycle until the study medication has been applied to each 
identified Wart up to 3 times. 
• 
If severe erythema and edema develop, then the treatment cycle should be discontinued for 
that specific treatment application. 
• 
Absorb any remaining A-101 study medication and dry the common wart and the surrounding 
skin without wiping or rubbing. 


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10.8. 
Dose Modification 
If a subject refuses to have a study medication treatment the investigator must report the visit 
number, visit date, and state the reason the subject refused to allow treatment in the subject’s 
CRF. 
If the subject’s refusal is associated with an AE, the investigator must also report the event on the 
appropriate CRF. 
10.9. 
Breaking the Blind 
The blind may be broken ONLY in the event of a medical emergency, in which knowledge of the 
study medication identity is critical to the management of the subject’s course of treatment.  
Before breaking the blind, the investigator should determine that the information is necessary.  In 
many cases, particularly when the emergency is clearly not study medication-related, the 
problem may be effectively managed by assuming that the subject is receiving an active study 
medication without the need for unblinding. 
If deemed necessary to break the blind for a study subject, attempt to contact the Medical 
Monitor to obtain permission to break the blind of a particular subject.  If it is not possible to 
contact the Medical Monitor beforehand, contact her/him as soon as possible after breaking the 
blind for a subject. 
  
 


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11. 
PREVIOUS AND CONCOMITANT THERAPIES 
11.1. 
Previous Therapy 
During Visit 1, the investigator or designee will question the subject to ensure they have not used 
any excluded therapies within the specified period prior to Visit 2 to the identified common 
warts: 
• 
Intralesional Therapy 
o Immunotherapy (e.g., Candida antigen, mumps antigen, Trichophyton antigen); 8 weeks 
o Anti-metabolite therapy (e.g., bleomycin, 5-fluorouracil); 8 weeks 
• 
Systemic Therapy 
o Immunomodulatory/immunosuppressant therapy (e.g., etanercept, alefacept, 
infliximab); 16 weeks 
o Glucocortico-steroids (inhaled and intra-nasal steroids are permitted); 28 days 
• 
Topical Therapy 
o LASER (e.g., pulsed-dye laser [PDL], light (e.g., intense pulsed light [IPL], photodynamic 
therapy [PDT], other energy-based therapy); 6 months 
o Immuno-therapy (e.g., imiquimod, squaric acid dibutyl ester [SADBE], etc.); 12 weeks 
o Antimetabolite therapy (e.g., 5-fluorouracil); 8 weeks 
o Retinoids; 90 days 
o Liquid nitrogen, electrodesiccation, curettage; 60 days 
o Over-the-counter (OTC) wart therapies and cantharidin; 28 days 
11.2. 
Concomitant Therapies 
Concomitant therapies are any new or existing therapy received from Visit 1 until discharge from 
the study. 
Concomitant therapies include drug (e.g., prescription, over-the-counter [OTC]) and non-drug 
(e.g., chiropractic, physical therapy, energy-based treatments) therapies. Subjects will refrain 
from receipt of any therapy in compliance with the inclusion/exclusion criteria. Subjects should 
refrain from changing the use of any concomitant therapies during the study. 
All new or modified concomitant therapies used during the study must be recorded in the subject 
CRF. 


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11.3. 
Prohibited Therapies 
During the course of this study, subjects are prohibited from using the following treatment 
therapies to treat the identified common warts: 
• 
Intralesional Therapy 
o Immunotherapy (e.g., Candida antigen, mumps antigen, Trichophyton antigen)  
o Anti-metabolite therapy (e.g., bleomycin, 5-fluorouracil);  
• 
Systemic Therapy 
o Immunomodulatory/immunosuppressant therapy (e.g., etanercept, alefacept, 
infliximab);  
o Glucocortico-steriods (inhaled and intra-nasal steroids are permitted);  
• 
Topical Therapy 
o LASER (e.g., pulsed-dye laser [PDL], light (e.g., intense pulsed light [IPL], photodynamic 
therapy [PDT], other energy-based therapy);  
o Immuno-therapy (e.g., imiquimod, squaric acid dibutyl ester [SADBE], etc.);  
o Anti-metabolite therapy (e.g., 5-fluorouracil);  
o Retinoids;  
o Liquid nitrogen, electrodesiccation, curettage;  
o Over-the-counter (OTC) wart therapies and cantharidin. 
The investigator should notify the Medical Monitor immediately if any prohibited therapies are required 
to ensure subject safety. 
 
Starting with Visit 2, subjects must not apply any topical products (e.g., moisturizers, sunscreens, 
etc.) to their identified common warts within 12 hours prior to any study visit (Note: routine 
cleansing products are allowed). 
 
After the completion of any study visit where a study medication treatment was performed 
subjects must NOT wash/submerge the treated common wart for at least 6 hours and must not 
apply any topical products to the treated common wart for at least 6 hours. Parents/legal 
guardians of children must ensure that the child does not put the treated area in their mouth, or 
eyes, until completely dry after the application. If the treated area is not completely dry 10 
minutes after the application, the area should be blotted dry. 
 


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12. 
ASSESSEMENTS OF CLINICAL EFFICACY 
12.1. 
Common Wart Identification 
At Visit 1, the investigator will identify at least one 1 and up to 6 common warts for treatment 
and evaluation. 
At Visit 1, each identified common wart must: 
• 
Have a longest axis that is ≥3 mm and ≤8 mm 
• 
Have a thickness ≤3mm 
• 
Be a discrete lesion, i.e. each wart meeting the entry criteria must be clearly 
separated from other warts  
• 
Be present for at least 4 weeks 
• 
Not be a periungual, subungual, genital, anal, mosaic, plantar, flat or filiform wart 
• 
Not be in an intertriginous fold 
• 
Not be covered with hair which, in the Investigator’s opinion, would interfere with the 
study medication treatments or the study evaluations  
Not be in an area that may be occluded (e.g., by clothing or footwear or in a skin fold). 
Record the location of each identified common wart on the body charts in the CRFs indicating 
landmarks and distances to assist with confirming the location of the identified common wart at 
subsequent visits. 
 
 


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12.2. 
Standardized Photography 
At Visits 1, 2, 4, 6, 9-13 a qualified investigational center staff member will take standardized 
color photographs of each identified common wart.  
Subjects at a sub-set of investigational sites (up to 3) will have additional standardized 
photographs taken of their each identified common wart at the following time-points: 
• V2:  10 minutes post application 
• V2:  1-hour post application 
• V2:  24-hour post application 
The photographs are to document the appearance and location of the each identified common 
wart.  The subject’s identity will not be revealed in the study photographs. 
At Visit 2, the photographs must be taken prior to the study medication application. 
Care must be taken to ensure the same lighting, background, subject positioning relative to the 
camera and camera settings are used for each photograph. 
Sites will be provided with photography equipment and supplies necessary for obtaining the 
common wart photographs.  Detailed instructions for obtaining and managing the photographs 
will be documented in the study specific Photography Manual and provided to the site at the 
study initiation visit.


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12.3. 
Physician’s Wart Assessment (PWA) 
The Physician’s Wart Assessment (PWA) is the Investigator’s assessment of the severity of each 
identified common wart at a particular time point. The Investigator should NOT refer to any other 
assessments to assist with this evaluation. This evaluation IS NOT a comparison with the PWA 
performed at any other visit. 
 At every study visit, the Investigator will assess each identified common wart and report the one 
integer that best describes the common wart severity using the following scale. At any visit where a 
study medication treatment is performed, the PWA must be completed prior to the treatment 
visit. 
Physician’s Wart Assessment  
Grade 
Descriptor 
0 
Clear: No visible wart.  No further treatment is indicated  
 
1 
Near Clear:  a visible wart that is less than 3 mm in maximal diameter (or length) 
2 
A visible wart ≥ 3 mm and < 6 mm in maximal diameter (or length) 
3 
A visible wart ≥ 6 mm in maximal diameter (or length) 
The physician is encouraged to use a ruler or caliper and to feel the wart or skin area to help his/her 
assessment. 
At Visit 1 for the subject to be enrolled and at Visit 2 for the subject to be randomized each identified 
wart must have a PWA grade ≥ 2. 
At Visits 3-9, identified common warts must have a PWA > 0 to be retreated. If the Investigator 
cannot assess the PWA for a common wart (e.g., the common wart cannot be visualized because of 
an LSR such as edema, scabbing, etc.) she/he must report the reason in the subject’s CRFs. The 
identified common wart must not be retreated at that visit, and the subject should be seen at the next 
scheduled visit.  All at home treatment visits will be based on the PWA score during the in-office 
visit.   
Refer to Appendix 2 for the PWA Site Manual.   
12.4. 
Subject Instructions 
An investigational center staff member will dispense a Subject Instruction Sheet to each subject 
at Visit 1 (Refer to Appendix 1). 
Throughout the study, the subjects should: 


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• 
Continue their routine cleansing regimen except they should avoid vigorous scrubbing of the 
identified common warts (e.g., loofah, back brushes, scrubbing straps, abrasive washcloths, 
sponges and cleansing pads, etc.) 
• 
Continue their routine cosmetics and skin care products 
• 
Avoid exposing the identified common warts to excessive natural or artificial ultraviolet radiation 
(e.g., sunlight, tanning beds) and use sunscreen on the common warts, if excessive exposure 
cannot be avoided 
• 
Avoid activities that might irritate the common warts. 
• 
Avoid the use of self-tanning lotions and spray tans near the common warts. 
• 
Bring the subject instruction sheet and subject diary with them to each visit. 
• Follow all instructions for the proper application of the A-101 study medication when 
applying product at home. 
On study visit days, the subjects should: 
• 
Wear loose fitting clothing to the visit (Note: clothing that comes in contact with the study 
medication may be bleached) 
• 
Starting with Visit 2, not apply any topical products to the identified common wart within 12 hours 
prior to the visit (Note: routine cleansing products are allowed) 
• 
After the completion of any study visit where a study medication treatment was performed DO 
NOT: 
o Wash/submerge the treated common wart for at least 6 hours 
o Apply any topical products to the treated common wart for at least 6 hours. 
12.5. 
Parents/legal guardians of children must ensure that the child does not 
put the treated area in their mouth, or eyes, until completely dry after the 
application. If the treated area is not completely dry 10 minutes after the 
application, the area should be blotted dry.Other Study Supplies 
Aclaris Therapeutics, Inc. will provide: 
• An appropriate ruler, or other instrument, for measuring of all common wart dimensions;  
• Supplies and instructions for collecting, labeling, shipping and result reporting for the clinical 
laboratory tests from ACM Laboratories; 
• Nitrile examination gloves 
• Equipment, supplies and training for taking standardized photographs; 


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13. 
ASSESMENT OF SAFETY 
In addition to reporting adverse events throughout the study the investigator, a designated and 
appropriately trained staff member or the subject, will perform the following safety assessments 
according to the schedules noted below. 
13.1. 
Local Skin Reactions (LSRs) 
The LSR assessment is the Investigator’s assessment of the signs and the subject’s assessment of the 
symptoms associated with irritation at the identified common wart site (i.e., the common wart and the skin 
immediately surrounding the common wart exposed to study medication). The Investigator may refer to 
previous photographs to assist with these assessments only AFTER the PWA has been performed. 
The Local Skin Reaction signs to be assessed are: 
• 
Erythema 
• 
Edema 
• 
Erosion 
• 
Ulceration 
• 
Vesicles/bullae 
• 
Excoriations 
• 
Scabbing 
The Local Skin Reaction symptoms to be assessed (by the Subject) are: 
• 
Stinging/burning 
• 
Pruritus (itch) 
At Visits 2-13, the Investigator will evaluate the LSR signs at the each identified common wart site as 
follows: 
• 
At visits where a study medication treatment or retreatment is performed: 
o Perform an LSR assessment prior to any study medication application 
and 
At Visits 2-13, the Subject will assess the LSR symptoms at the identified common wart site as follows: 
• 
At visits where a study medication treatment or retreatment is performed: 
o Perform an LSR assessment prior to any study medication application 
 
At visits where NO study medication treatment is performed: 


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o Perform an LSR assessment. 
The Investigator and Subject should report the one integer that best describes the severity of each 
LSR sign or LSR symptom for the common wart site using the scale below:


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Local Skin Reactions 
Grade 
Descriptor 
0 
None; No signs or symptoms present. 
1 
Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated. 
2 
Moderate; minimal, local or noninvasive intervention indicated. 
3 
Severe or medically significant but not immediately life threatening; disabling; limiting 
self-care of activities of daily living. 
13.2. 
Vital Signs 
Vital signs will be measured by a qualified staff member at Visit 1, Visit 9 and Visit 13. The following 
items will be measured: 
• 
Body temperature; 
• 
Heart rate; 
• 
Respiration rate; 
• 
Blood pressure (systolic and diastolic) after the subject sits quietly for at least 5 minutes; 
• 
Height (at Visit 1 only); 
• Weight (at Visit 1 only); 
Any measure that is, in the opinion of the investigator, abnormal AND clinically significant (CS 
must be recorded as history if found prior to the first study medication treatment or as an AE if 
found after the first study medication treatment begins. 
13.3. 
Clinical Laboratory Sampling 
Non-fasting blood samples for clinical laboratory analysis will be collected by a qualified staff 
member at Visit 1 and Visit 13. Approximately 7.5 mL of blood will be collected for each 
chemistry sample and 3 ml of blood will be collected for each complete blood count (CBC). 
These blood samples will be sent to a central laboratory for analysis.  Refer to the study specific 
laboratory manual for instructions regarding handling of the blood samples and shipping 
instructions. 
The following tests, at a minimum, will be conducted: 
 
Chemistry Panel 
Complete Blood Count 
Albumin 
Hematocrit 


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Alkaline phosphatase 
Hemoglobin 
Alanine aminotransferase (ALT) 
Platelet count 
Aspartate aminotransferase (AST) 
Red blood cell morphology 
Blood urea nitrogen (BUN) 
Red blood cell count 
Bicarbonate 
White blood cell count 
Calcium 
White blood cell differential 
Chloride 
    % & absolute 
Creatinine 
    Basophils 
Glucose 
    Eosinophils 
Lactate dehydrogenase (LDH) 
    Lymphocytes 
Phosphorus 
    Monocytes 
Potassium 
    Neutrophils 
Sodium 
 
Total bilirubin 
 
Total protein 
 
Uric acid 
 
The results of the clinical laboratory tests will be reported on the central laboratory’s standard 
reports. These laboratory results will be sent to the investigator via fax.  The investigator must 
review all laboratory reports in a timely manner and note NCS or CS to define the clinical 
relevance of any result that is outside the normal range for the laboratory. The investigator must 
date and initial every laboratory report. 
The investigator must review the Visit 1 laboratory results for all the measured analytes for each 
subject prior to Visit 2. The subject must not be randomized at Visit 2 if any of the Visit 1 results 
are outside normal range for the laboratory AND, in the opinion of the investigator, CS. 
The investigator must report all laboratory results that are BOTH outside the normal range for 
the laboratory AND, in the opinion of the investigator, CS as medical history if found prior to the 
first study medication treatment or as an AE if found after the first study medication treatment 
begins. 
13.4. 
Demographics and Medical History 
At Visit 1, the investigator or designee will collect demographic information including date of 
birth, sex at birth, race and, if appropriate, ethnicity for each subject. 


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At Visit 1, the investigator must determine each subject’s Fitzpatrick skin type and document 
appropriately on the subject’s CRF. 
Table 4: 
Fitzpatrick Skin Type Scoring System 
Skin Type 
Classification 
Description 
Type I 
always burns, never tans (pale white; blond or red hair; 
blue eyes; freckles) 
Type II 
usually burns, tans minimally (white; fair; blond or red 
hair; blue, green, or hazel eyes) 
Type III 
sometimes mild burn, tans uniformly (cream white; fair 
with any hair or eye color) 
Type IV 
burns minimally, always tans well (moderate brown) 
Type V 
very rarely burns, tans very easily (dark brown) 
Type VI 
Never burns, never tans (deeply pigmented dark brown to 
darkest brown) 
(Fitzpatrick, TB, 1988) 
Medical history information will be recorded including all medical conditions and disease states that, at 
Visit 1: 
• 
Are ongoing 
• 
Require concomitant therapy 
Are, in the opinion of the investigator, relevant to the subject’s study participation. 


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14. 
ADVERSE EVENTS 
14.1. 
Definitions 
14.1.1. 
Adverse Events (AEs) 
An adverse event (AE) is any untoward medical occurrence in a patient that develops or worsens 
in severity during the conduct of a clinical study of a pharmaceutical product and does not 
necessarily have a causal relationship to the study drug.  An adverse event can, therefore, be any 
unfavorable and unintended physical sign, symptom, or laboratory parameter that develops or 
worsens in severity during the course of the study, or significant worsening of the disease under 
study (or any concurrent disease), whether or not considered related to the study drug.  
Accordingly, an adverse event could include any of the following: 
• intercurrent illnesses; 
• physical injuries; 
• events possibly related to concomitant medication; 
• significant worsening (change in nature, severity, or frequency) of the disease under 
study or other pre-existing conditions.  (NOTE: A condition, recorded as pre-existing, 
that is intermittently symptomatic [e.g., headache] and which occurs during the study 
should be recorded as an adverse event); 
• Drug interactions; 
• Events occurring during diagnostic procedures or any washout phase of the study; 
• laboratory or diagnostic test abnormalities occurring after the start of the study (i.e., 
after screening and once confirmed by repeat testing) that results in the withdrawal of 
the patient from the study, requires medical treatment or further diagnostic work-up, 
or is considered by the study investigator to be clinically significant.  NOTE: 
Abnormal laboratory test results at the screening visit that preclude a patient from 
entering the study or receiving study treatment are not considered adverse events, but 
will be recorded to monitor data from patients who do not meet screening criteria. 
Worsening of any of the identified common wart assessments should be reported as an 
AE ONLY if the use of the study medication is interrupted or discontinued or if therapy 
is required to manage the event. 
The investigator must, for any common wart related AE, question the subject in detail 
to determine if there are any confounding factors (e.g., irritation by clothing or activity, 
sunburn) for any such AE. 
The investigator should, when certain, report a diagnosis rather than the signs, symptoms or 
clinically relevant abnormal laboratory values associated with the AE. Otherwise, signs, 
symptoms or abnormal laboratory values may be used to describe the AE. 
Any CS abnormality discovered prior to the first study medication treatment should be 
reported as medical history, not as an AE. 


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14.1.2. 
Serious Adverse Events (SAEs) 
A Serious Adverse Event is any untoward medical occurrence that at any dose: 
• 
Results in death; 
• 
Is life threatening; 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization; 
• 
Results in persistent or significant disability/incapacity,  
• 
Is a congenital anomaly/birth defect or 
• 
Is an important medical event. 
 
The term “life threatening” refers to an event in which the subject was at risk of death at the time of 
event; it does not refer to an event that hypothetically might have caused death if it was more severe. 
 
Inpatient hospitalization is considered to have occurred if the subject is admitted to the hospital on an in-
patient basis, even if released the same day. Prolongation of hospitalization is defined as an additional 
night stay in the hospital. Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
 
Important medical events are those that may not be immediately life threatening, result in death or 
hospitalization, but are clearly of major clinical significance and may jeopardize the subject or require 
intervention to prevent one of the outcomes listed in the SAE definition above. These should also usually 
be considered serious. Examples of such events are intensive treatment in an emergency room or at home 
for allergic bronchospasm, blood dyscrasia or convulsions that do not result in hospitalization. 
 
14.1.3. 
Adverse Event Reporting Period 
The investigator must start reporting non-serious AEs starting with the subject’s first study 
medication treatment continuing until Visit 11. Non-serious adverse events that occur between 
the time the subject was consented and the first application of study medication will be reported 
as medical history. 
Reporting for SAEs begins after the subject signs the informed consent and continues until Visit 
11 (regardless of relationship to study medication).  If a subject experiences a SAE after Visit 11 
that is deemed by the investigator to be related to study medication, the investigator must report 
this to the Sponsor using the study specific SAE report form. 
14.1.4. 
Severity 
The investigator must define the severity of each AE using the following definitions as a 
guideline. The investigator will consider the range of the possible severity of the event and 
identify the severity that is the most appropriate according to her/his medical judgment. 
Mild – Awareness of signs or symptom, but easily tolerated 
Moderate – Discomfort, enough to cause interference with usual activity 


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Severe – Incapacitating with inability to perform usual activity. 
14.1.5. 
Relationship to Study Medication 
The investigator will determine if there is a reasonable causal relationship between the study 
medication and an AE or not. The investigator will use her/his best medical judgment and 
consider all relevant factors (e.g., temporal relationship, location of the event, the subject’s 
relevant medical history, concomitant therapies and concurrent conditions) to determine the 
relationship of the AE to the study medication. The investigator will define the relationship of an 
AE to the study medication by selecting one of the following categories. 
Related – There is a reasonable possibility that there is a causal relationship between the study 
medication and the AE. 
Not Related – There is not a reasonable possibility that there is a causal relationship 
between the study medication and the AE. 
The term “reasonable causal relationship” means there are facts or arguments to suggest a causal 
relationship (International Conference on Harmonization (ICH) E2A. 
14.2. 
Reporting Procedures 
14.2.1. 
Procedures for Reporting Adverse Events 
At each post enrollment visit, the investigator or designee will question the subject to elicit AEs 
using a non-directive question such as “Has there been any change in your health since the 
previous study visit?”   
The Investigator/designee will monitor the subject for at least 20 minutes after the Treatment 
Completion Time at any visit during which a study medication treatment is performed to elicit 
AEs in a similar manner. 
If appropriate, based on the subject’s response to non-directed questioning regarding AEs, the 
investigator or designee will follow-up with directed questions and appropriate evaluations. 
Any AE noted during the reporting period must be reported in the source documents and on the 
appropriate AE CRF. 
AEs that are defined as “Not Related” to the study medications will be followed until they are 
resolved or until the subject’s last study visit. AEs that are defined as “Related” to the study 
medications will be followed until they are resolved or, if not resolved after the subject’s last 
study visit, until in the opinion of the investigator, the AE reaches a clinically stable outcome 
with or without sequelae. 
14.2.2. 
Procedure for Reporting Serious Adverse Events 
Upon becoming aware of a SAE occurring during the AE reporting period, whether or not related 
to the study medications, the investigator must: 
1. 
Take the appropriate medical action to ensure the subject’s safety 


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2. 
Immediately inform Aclaris of the SAE: 
Serious Adverse Event Facsimile:  484-324-2359 
 
3. 
Within 24-hours of becoming aware of the event, a SAE report form, an AE CRF and any other 
relevant information (e.g., concomitant medication CRF, medical history CRF, laboratory test 
results) must be faxed to the SAE Fax line listed above. 
4. 
Monitor and document the progress of the SAE until it resolves or, if not resolved after the subject’s 
last study visit, until in the opinion of the investigator the AE reaches a clinically stable outcome 
with or without sequelae AND the investigator and Drug Safety Monitor agree that the SAE is 
satisfactorily resolved. 
5. 
Inform the Drug Safety Monitor of SAE updates by telephone followed by an SAE form update sent 
by fax or by e-mail. 
Comply with the appropriate regulatory requirements and Aclaris Therapeutics, Inc. instructions 
regarding reporting of the SAE to the responsible Institutional Review Board (IRB) or Ethics 
Committee (EC). 
14.2.3. 
Withdrawal Due to an Adverse Event 
Any patient who experiences an adverse event may be withdrawn from study drug at any time at 
the discretion of the investigator.  If a patient is withdrawn wholly or in part because of an 
adverse event, both the adverse events page and termination page of the CRF will be completed 
at that time.  The patient will be monitored until the event has resolved or stabilized, until a 
determination of a cause unrelated to the study drug or study procedure is made, or until the 
patient is referred to the care of a local health care professional.  The investigator must inform 
the medical monitor as soon as possible of all patients who are being considered for withdrawal 
due to adverse events.  Additional reports must be provided when requested. 
 


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15. 
STATISTICAL CONSIDERATIONS 
15.1. 
Sample Size and Power Considerations 
 Based on efficacy results from study A-101-WART-203 with the same active study medication 
and treatment plan specified in the current protocol for a comparable patient population and 
indication, an overall per-wart clearance rate of at least 26% for Active compared with 9% for 
Vehicle is anticipated.  Assuming a distribution of treated warts per subject comparable to the 
Phase 2 study results, statistical modeling provided a forecast of an advantage in subject 
responder rates (all treated warts with PWA=0) for Active over Vehicle groups of at least 11 
percentage points.  This leads to a required sample size for the current study of approximately 
500 subjects to provide greater than 90% power to achieve statistical significance in the primary 
efficacy analysis. This projection takes into account the impact of the anticipated subject dropout 
rate on power for the primary efficacy analysis, based on the Intent-to-Treat (ITT) population 
and planned missing data imputation procedures.  
Additionally, a simulation was conducted in a manner that accounted for the distribution of 
multiple warts, the treatment effect in clearance between the different warts and the correlation 
in wart clearance among multiple warts.  Specific details of the simulation are described in the 
SAP.  Results of this simulation indicate that data from 500 subjects (250 per group) will provide 
97% power to demonstrate the superiority of 45% A-101 topical solution over vehicle for the 
primary endpoint. 
15.2. 
Analysis of Populations 
The populations used for analyses will be defined as follows: 
• Intent-to-Treat Population (ITT): The ITT population includes all randomized subjects.  
• Per-Protocol Population (PP):  The PP Population includes all subjects who received at 
least one application of study medication and have no major protocol violations. 
• Safety Population: The Safety population includes all subjects who received at least one 
application of study medication. 
15.3. 
Statistical Analysis of Efficacy 
The ITT population will be used for primary and secondary efficacy analyses and summaries.  
The ITT population is defined as all subjects randomized to the study and analyzed as 
randomized.  The Per-Protocol (PP) population will be used for sensitivity analyses for the 
primary efficacy analysis and all secondary efficacy analyses included in the hierarchical testing 
procedure.   Details on all analyses discussed below will be provided in the study Statistical 
Analysis Plan (SAP).  
The primary efficacy analysis will be a treatment comparison of A-101 45% compared to 
Vehicle at Visit 10 (Day 60).  It will be based on the proportion of subjects who achieve 
complete clearance (PWA=0) of all identified common warts.  A Cochran Mantel Haenszel 
(CMH) test stratified by the baseline number of treated warts will be used to perform the primary 


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efficacy comparison between treatment groups, with 2-tail alpha set at 0.05.  The analysis will be 
based on the ITT population.  Any identified common wart for a randomized subject that has 
missing data at the endpoint visit will be treated as not Clear for the purpose of the primary 
efficacy analysis.   
The first sensitivity analysis for the primary endpoint will be an analysis based upon the PP 
population.  This analysis will use the same CMH model described for the primary analysis.  A 
second sensitivity analysis will be conducted for the primary endpoint using the same CMH 
model for the ITT population that includes the imputation of missing PWA data using a fully 
conditionally specified (FCS) regression-based Multiple Imputation (MI) procedure. To assess 
the impact of missing data imputation on the primary analysis results a tipping point analysis will 
be conducted.  This analysis will shift the treatment coefficient in the regression model used in 
the MI procedure to impose a worse mean maximum PWA for the A-101 45% arm and a better 
mean maximum PWA for the vehicle arm.  Details of this tipping point analysis will be specified 
in the SAP.  In addition, a model similar to the primary analysis model but stratified instead by 
Study Center will be performed as a sensitivity analysis including a Breslow-Day test to evaluate 
heterogeneity across sites.   
Four secondary efficacy analyses will be performed and tested in a hierarchical Fixed-Sequence step-
down method to control alpha among secondary efficacy variables.  The predefined order of the tests is 
specified to be the order of these analyses as presented below.  All analyses will be conducted at the 
same alpha level (2-tail alpha = 0.05).  The results of the second analysis will only be reported if the first 
analysis reaches statistical significance at alpha = 0.05.  The results of the third analysis will only be 
reported if the first and second analyses reach statistical significance, each at alpha = 0.05.  The results 
of the fourth analysis will only be reported if the first, second and third analyses reach statistical 
significance, each at alpha = 0.05.  Each of the analyses will focus on the outcome of identified common 
warts at specified time points.   
The first secondary analysis will evaluate the effectiveness of A-101 45% compared to Vehicle at Visit 13 
(Day 137).  It will be based on the proportion of subjects who achieve complete clearance (PWA=0) of all 
identified common warts.  A Cochran Mantel Haenszel (CMH) test identical to the primary efficacy 
analysis model and stratified by the number of treated warts at baseline will be used to perform the 
comparison between treatment groups, with 2-tail alpha set at 0.05.  Any randomized subject with 
missing data at the Day 137 visit will be treated as not Clear for the purpose of this secondary efficacy 
analysis. Sensitivity analyses specified for the primary efficacy analysis will also be performed for this 
efficacy time point, including missing data imputation impact analyses, the tipping point analysis, and 
the site heterogeneity analysis.       
The second secondary efficacy analysis will be based on a comparison between A-101 45% and 
Vehicle of the mean per-subject percent of treated warts that are Clear (PWA=0) at Visit 13 (Day 
137), using an analysis of variance (ANOVA) model with 2-tail alpha set at 0.05. 
The third secondary efficacy analysis will be a comparison between A-101 45% and Vehicle of 
the proportion of subjects with a single wart at baseline, whose wart is Clear (PWA=0) at Visit 
10, using a CMH test stratified by investigator site, with 2-tail alpha set at 0.05. 


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The fourth secondary efficacy analysis will a comparison between A-101 45% and Vehicle s 
with respect to the median time to achieve onset of Clearance (PWA=0) for all treated warts.  It 
will be conducted as a comparison of median time for a subject to first achieve Clearance 
(PWA=0) of all treated warts, using a log rank test with 2-tail alpha set at 0.05.  This will be a 
Kaplan-Meier time-to-event analysis providing standard survivor functions and comparisons of 
time-to-event curves using the log rank test, where time-to-event curves will be compared with 
two-tail alpha = 0.05, and median time to event will be presented for each treatment group. For 
each subject the time to achieve onset of complete treated wart Clearance will be calculated from 
the date of randomization to the earliest visit date when all treated warts are clear.  In the event a 
subject does not attain complete wart Clearance, that subject’s time-to-event data will be treated 
as censored for the Kaplan-Meier analysis.    
15.4. 
Statistical Analysis of Safety Data 
Descriptive statistics will be calculated on the safety parameters using the Safety Population and using 
actual treatment received. The proportion of subjects with treatment-emergent adverse events will be 
tabulated and presented by treatment and Medical Dictionary for Regulatory Activities (MedDRA) 
System Organ Class. Vital signs, LSR scores and clinically relevant abnormal laboratory results will also be 
tabulated and presented by study medication. No inferential testing will be performed. 
 
 Safety summaries by study medication group will include listings by study medication of adverse events 
incidences within each MedDRA System Organ Class, and changes from pre-application values in vital 
signs. Adverse event summaries will be presented by study medication showing the proportion of 
subjects experiencing adverse events, both overall and by MedDRA System Organ Class.  The version of 
MedDRA to be used for the analysis of this study will be specified in the Statistical Analysis Plan. 
15.5. 
Interim Analysis 
No interim analyses are planned for this study.  


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16. 
QUALITY CONTROL AND QUALITY ASSURANCE 
16.1. 
Protocol Amendments 
No changes from the final approved (signed) protocol will be initiated without the prior written 
approval or favorable opinion of a written amendment by the IRB/EC, except when necessary to 
eliminate immediate safety concerns to the study subjects or when the change involves only 
logistics or administration.  The principal investigator and the sponsor will sign the protocol 
amendment. 
16.2. 
Protocol Violations 
A protocol violation is defined as any divergence from the protocol-specific inclusion/exclusion 
criteria, subject is administered a prohibited medication, and/or GCP guidelines.  Protocol 
violations will be identified and recorded, by study center personnel, on the CRF. 
As a matter of policy, sponsor/CRO will not grant exceptions to protocol-specific entry criteria 
to allow patients to enter a study.  If under extraordinary circumstances such action is considered 
ethically, medically, and scientifically justified for a particular patient, prior approval from 
sponsor/CRO and the responsible IRB/IEC, in accordance with the Sponsor/CROs Standard 
Operating Procedure (SOP), is required before the patient will be allowed to enter the study.  If 
investigative center personnel learn that a patient who did not meet protocol eligibility criteria 
was entered in a study (a protocol violation), they must immediately inform sponsor/CRO.  Such 
subjects will be discontinued from the study, except in a rare instance following review and 
written approval by sponsor/CRO and the responsible IRB/IEC, according to the applicable SOP. 
16.3. 
Training 
For each investigational center, there will be an initiation visit prior to enrolling any study 
subjects. 
It is strongly recommended that all investigators, other evaluators, study nurses, study 
coordinators or other applicable personnel attend this visit.  During this visit, participants will be 
trained to the protocol, study specific procedures, and the CRFs.  Those unable to attend the 
initiation visit must receive on-site training from an appropriately trained individual prior to 
participating in any of the procedures and evaluations in this study. 
Clinical Research Associates (CRAs) and other applicable personnel will be trained prior to 
study initiation to familiarize CRAs with the disease, the Standard Operating Procedures (SOPs), 
the protocol and other study specific items.  Team organization, communication and operational 
issues will also be discussed. 
Aclaris Therapeutics, Inc. will provide an investigational center file to each center. 
16.4. 
Monitoring 
The conduct of the study will be closely monitored by the Aclaris Therapeutics, Inc. study 
monitor /CRO to verify adherence to ICH Good Clinical Practice (GCP) guidelines, applicable 
SOPs, the protocol, other written instructions and regulatory guidelines. 


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The investigator will allow the Aclaris Therapeutics, Inc. representatives designee and/or and 
any regulatory agency to have direct access to all study records, CRFs, corresponding subject 
medical records, study medication dispensing records and study medication storage area, and any 
other documents considered source documentation.  The investigator also agrees to assist the 
representative, if required. 
16.5. 
Data Management 
Data will be collected using CRFs that are specifically designed for this study.  The data 
collected on the CRFs will be captured in a clinical data management system (CDMS) that meets 
the technical requirements described in US 21 Code of Federal Regulations (CFR) Part 11.  The 
CDMS will be fully validated to ensure that it meets the scientific, regulatory, and logistical 
requirements of the study before it is used to capture data from this study.  Before using the 
CDMS, all users will receive training on the system and study specific training.  After they are 
trained, users will be provided with individual system access rights. 
The handling of data, including data quality assurance, will comply with regulatory guidelines, 
including ICH and GCP, and the sponsor/CRO SOPs and working instructions.  Data 
management and control processes specific to this study will be described in a data management 
plan.    At the end of the study, the database will be locked and the data will be released for 
reporting and statistical analysis. 
16.6. 
Quality Assurance 
The study is conducted under the sponsorship of Aclaris Therapeutics, Inc. in compliance with 
the applicable regulatory requirements as well as applicable ICH guidelines, Helsinki 
Declaration, and in respect of the Aclaris Therapeutics, Inc. and/or sub-contractor SOPs for study 
conduct and monitoring. 
Audits may be carried out by the Aclaris Therapeutics, Inc. or Aclaris Therapeutics, Inc.’s 
representatives and inspections may be performed by regulatory authorities or IRB/ECs before, 
during or after the study.  The investigator will provide the auditing/inspecting group direct 
access to all study records (e.g., CRFs, subject medical records, study medication dispensing 
records) and the investigational center study facilities. The investigator and study staff will be 
available and will assist the auditing/inspecting groups as appropriate. 
16.7. 
Record Retention 
All pertinent data, samples, photographs, correspondence, original or amended protocol, reports 
and all other material relating to the study will be maintained securely in Aclaris Therapeutics, 
Inc./CRO/investigator archives for the legally required duration for archiving. 
The investigator should maintain the essential study documents as specified in ICH GCP, and in 
compliance with all regulatory requirements. The investigator should ensure these documents are 
protected from accidental destruction or disposal. 
If the Investigator needs to re-assign responsibility for maintaining these documents (e.g., due to 
retirement) it must be transferred to a person willing to accept this responsibility.  The 


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investigator must notify Aclaris Therapeutics, Inc., in writing, of the name and address of the 
new individual. 
If the Investigator cannot guarantee this archiving requirement at the investigative site for any or 
all of the documents, special arrangements must be made between the Investigator and the 
Sponsor to store these in sealed containers in an off-site storage location so that they can be 
returned to the Investigator in case of a regulatory audit.  Where source documents are required 
for the continued care of the patient, appropriate copies will be made for off-site storage.  
No trial document should be destroyed without prior written agreement between the Sponsor and 
the Investigator. Should the Investigator wish to assign the trial records to another party or move 
them to another location, the Investigator must notify the Sponsor in writing of the new 
responsible person and/or the new location. 


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17. 
ETHICS AND GENERAL STUDY CONDUCT 
CONSIDERATIONS 
17.1. 
Institutional Review Board (IRB)/Ethics Committee (EC) 
This protocol and any accompanying material, including information that will be provided to 
prospective patients (such as advertisements, patient information sheets, or study descriptions 
used to induce study participation or obtain informed consent) must be submitted to the Central 
IRB for approval.  Approval of each such submission must be obtained from the committee 
before it may be used in the study and must be documented in a written notification to the 
Investigator specifying the protocol number, protocol version, documents reviewed, and date on 
which the committee met and granted the approval.  In particular, each informed consent 
document must bear clear evidence (written, stamp, date of approval, etc.) of IRB approval 
before it may be presented to prospective (or ongoing, as appropriate) study patients for 
signature. 
Written evidence of the approval must be made available to the Sponsor.  Any modifications 
made to the protocol and of correspondingly modified informed consent documents made after 
receipt of Central IRB approval must also be submitted to the committee for approval before 
implementation unless the modification is made on an emergency basis to protect the welfare of 
study patients.  In the latter case, the Central IRB must be notified promptly and their written 
approval must be obtained as soon after the fact as possible. 
Appropriate reports on the progress of the study will be made to the Central IRB and the Sponsor 
by the Investigator in accordance with applicable regulatory regulations and in conformity with 
policies established by both the Central IRB and the Sponsor.  The shortest time interval between 
required reports required by either party or by regulations will prevail. 
The Investigator at each investigative site, or his/her nominee, will be responsible for reporting 
any SAEs to the Central IRB as soon as possible, and in accordance with the guidelines of the 
Central IRB. 
The Sponsor will be responsible for reporting all serious, life threatening or fatal adverse study 
drug events with a causal relationship to the study drug to appropriate regulatory agencies within 
their required timelines. 
The Investigator is responsible for obtaining written, informed consent(s) from each prospective 
patient interested in participating in this study before performing any study-related procedures.  
Written informed consent must be obtained after adequate, thorough, and clear explanation of the 
aims, methods, objectives, and potential hazards of the study, as well as any use of the patient’s 
genetic information from the study.  The Investigator must use the most current Central IRB-
approved consent form for documenting written informed consent.  Each informed consent will 
be appropriately signed and dated by the patient and the person obtaining consent and each page 
not signed must be initialed and dated by the patient.  The investigational site must retain the 
original signed consent and provide a copy to the patient. 


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17.2. 
Ethical Conduct of the Study 
The Sponsor will use information developed in this clinical study in connection with the 
development of A-101 Solution and, therefore, may disclose it as required to other clinical 
Investigators participating in other studies and to regulatory agencies.  In order to allow the use 
of the information derived from this clinical study, the Investigator understands that he/she has 
an obligation to provide all data produced during this study to the Sponsor. 
The Sponsor considers that clinical data (complete or incomplete) constitute financially sensitive 
information.  Consequently, the Sponsor requires that discussion of results in any form, 
electronic, verbal, or written before study completion and full reporting should only be 
undertaken with the Sponsor’s prior written consent. 
Individual patients’ medical information obtained as a result of this study is considered 
confidential.  The Investigator and the study center will adhere to all applicable laws relating to 
the protection of patient information.  To assure that patients’ confidentiality is maintained, 
patients’ data will be identified by a study-assigned number. 
All Sponsor personnel will handle patients’ data in a confidential manner in accordance with 
applicable regulations governing clinical research.  Subjects’ records will be inspected only in 
connection with this research project.  Information generated as a result of a subject’s 
participation in this study may be disclosed to third parties for research and regulatory purposes 
in any country as determined by the Sponsor.  However, subjects will not be individually 
identified but will be referred to only by the study assigned number. 
17.3. 
Regulatory Documents 
The investigator must maintain a study file containing current and complete regulatory 
documentation in compliance with the current ICH E6 GCP guideline. This file will be reviewed 
as part of the routine monitoring for this study. 
17.4. 
Contractual Requirements 
A contractual agreement will be signed between Aclaris Therapeutics, Inc. and each investigator.  
This document will contain supplemental information, including financial terms, confidentiality, 
study schedule, third party responsibility, and publication rights. 
 
 
 


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18. 
REFERENCES 
1. Chan HP, Maibach HI, 2008.  "Hydrogen Peroxide, Blanching, and Skin: an Overview". 
Cutaneous and Ocular Toxicology, 307-309. 
2. Fitzpatrick, TB. 1988. "The Validity and Practicality of Sun Reactive Skin Types I 
through VI." Arch Dermatology 869-871. 
3. Richardson. 1866. "On the Introduction of Peroxide of Hydrogen as a Medicine." The 
Lancet 87 (2220):300. 
4. Richardson. 1891. "On Peroxide of Hydrogen, or Ozone, or Water as a Remedy: 
Continued from a Research Commenced in the Year 1858." The Lancet 137(3527):760-
763. 
5. Richardson. 1891. "On Peroxide of Hydrogen, or Ozone, or Water, as a Remedy: 
Continued from Research Commenced in the Year 1858." The Lancet 137(3526):707-709 
6. Schumb WC, Satterfield CN, and Wentworth RL. 1955. Hydrogen Peroxide. New York: 
Reinhold Publishing Comp. 
7. Watt BE, Proudfoot AT, Vale JA. 2004 . "Hydrogen Peroxide Poisoning (Review)." 
Toxicological Reviews 51-57. 
8. Zonios. 2007. "Probing Skin Interaction with Hydrogen Peroxide Using Diffuse 
Reflectance Spectroscopy." Physicis in Medicine and Biology 269-278. 
 


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APPENDIX 1. A-101-WART-302 SUBJECT INSTRUCTION SHEET 
Please follow these instructions carefully. Contact the study staff at the telephone number noted below 
if you have any questions about the study: 
Contact: 
 
 
 
 
 
   Telephone: 
                                     
THROUGHOUT THE STUDY: 
• 
Continue your routine cleansing regimen except avoid vigorous scrubbing of the identified 
common warts (e.g., abrasive cleansing pads, abrasive cleansers, etc.). 
• 
Continue your routine skin care products. 
• 
Avoid exposing the identified common warts to excessive natural or artificial ultraviolet radiation 
(e.g., sunlight, tanning beds) and use sunscreen on the wart, if excessive exposure cannot be 
avoided. 
• 
Avoid activities that might irritate the identified common warts. 
• 
Bring this subject instruction sheet and subject diary with you to each visit. 
 
STARTING WITH VISIT 2: 
• 
On visit days, do not apply any topical products (e.g., moisturizers, sunscreens) to the identified 
common wart, except for routine cleansing products, within 12 hours prior to the visit 
• 
After any study visit where a study medication treatment occurred do not: 
o Wash/submerge the treated common warts for at least 6 hours after the treatment 
o Apply any topical products to the treated common warts for at least 6 hours 
o Occlude, bandage or otherwise cover the common wart treatment area (loose-fitting clothing is 
permissible) for at least 6 hours. 
o Parents/legal guardians of children must ensure that the child does not put the treated area in 
their mouth, or eyes, until completely dry after the application. If the treated area is not 
completely dry 10 minutes after the application, the area should be blotted dry. 
 
STUDY MEDICATION:  The study medication provided to you is only to be used as instructed.   
Please ask your doctor or staff if you have any questions about its use. 
 
STUDY VISIT SCHEDULE: 
VISIT 2: 
VISIT 3: 


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Date:                            Time: 
Date:                            Time: 
VISIT 4: 
Date:                            Time: 
VISIT 5: 
Date:                            Time: 
VISIT 6: 
Date:                            Time: 
VISIT 7: 
Date:                            Time: 
VISIT 8: 
Date:                            Time: 
VISIT 9: 
Date:                            Time: 
VISIT 10: 
Date:                            Time: 
VISIT 11: 
Date:                            Time: 
VISIT 12: 
Date:                            Time: 
VISIT 13: 
Date:                            Time: 
 
 
 At Home Study Administration Days: 
 
• 
Do not apply any topical products (e.g., moisturizers, sunscreens) to the identified common 
wart, except for routine cleansing products, within 12 hours prior to the administration 
• 
After the application of the study medication do not: 
o Wash/submerge the treated common wart for at least 6 hours after the treatment 
o Apply any topical products to the treated common wart for at least 6 hours 
o Occlude, bandage or otherwise cover the common wart treatment area (loose-fitting clothing is 
permissible) for at least 6 hours. 
Parents/legal guardians of children must ensure that the child does not put the treated area in 
their mouth, or eyes, until completely dry after the application. If the treated 
area is not completely dry 10 minutes after the application, the area should be 
blotted dry. 
At Home Study Medication Application: 
 


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• 
Wash your hands prior to completing study medication treatment. 
• 
Visually inspect the applicator for damage. If the applicator appears damaged do not use it for 
the treatment. 
• 
Do not apply the study medications to eyes, nose, mouth, mucous membranes, or open wounds. 
• 
Wear nitrile examination gloves during the treatment that were provided to you by your doctor. 
Latex gloves are prohibited.  
• 
Thoroughly cleanse the identified common wart by firmly rubbing with a swab/wipe wetted with 
70% isopropyl alcohol that was provided to you by your doctor. 
• 
Using firm pressure and with the tip of the applicator held over the wart, squeeze in the middle 
of the applicator to apply one drop of study medication onto the identified common wart.  Using 
the smaller side of the applicator tip, firmly move the applicator around in a circular motion to 
fully saturate the lesion.  Apply the study medication for approximately 15 seconds. 
• 
Minimize exposure to the surrounding normal skin. 
• 
During the treatment process remove excess study medication from the surrounding skin using 
a clean absorbent wipe. 
• 
Ensure the each identified wart is fully saturated with study medication at the end of the 
approximately 15 second application. 
• 
Allow the treated wart to remain undisturbed for approximately 15 seconds. 
• 
After approximately 15 seconds repeat the approximately 15 second application process. 
• 
Repeat the application/waiting cycle until the study medication has been applied to the 
identified common wart up to 3 times. 
• 
Absorb any remaining A-101 study medication and dry the treated common wart and the 
surrounding skin without wiping or rubbing. 
• 
Document, in your treatment diary, the number of times the identified common wart is treated 
during a treatment.  
• 
After applying the study medication, the cap should be put back on the applicator, the used 
applicator should be put in one of the used nitrile gloves (after removal), knotted at the end and 
placed in a biohazard bag. The biohazard bag, with the used applicator in the glove, should be 
placed in the plastic bag you brought the applicator home in, and returned to the site for 
accountability.   


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Diagram Showing the Process for Preparing A-101 Study Medication  
 
1. The common wart should be cleaned using an alcohol wipe prior to application of A-101 
45%. 
2. Hold the  applicator so that the applicator cap is pointing up. 
3. Crush the ampule in the applicator by applying pressure to the center of the barrel of the 
applicator. 
4. Remove the sleeve. 
5. Tap the barrel of the applicator to ensure the solution is free of the crushed ampule. 
6. Gently remove the cap by twisting while pulling away from the applicator. 
7. Express a single drop of A-101 45% so that the tip of the applicator becomes wet. 
8. Apply the solution to the common wart in a circular motion. 


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APPENDIX 2. PWA SITE USER MANUAL 


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ICF_006.pdf: 
Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 1 of 13
INFORMATION AND CONSENT FORM
For Adults and Parents/Guardians of Minor Participants 
Study Title: 
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 
Study #:
Sponsor:
A-101-WART-301 
Aclaris Therapeutics, Inc.
Study Doctor:
<<investigator>>
<<firm name>>
<<street address>>, <<city>>, <<state>><<zip>>
Telephone Number: <<000-000-0000>>
After Office Hours:  <<000-000-0000>>
The study doctor wants to know if you would like to be part of a research study.
If you have any questions about or do not understand something in this form, you should ask 
the study doctor or study staff. You should also discuss your participation with anyone you 
choose in order to better understand this study and your options.
Participating in a research study is not the same as getting regular medical care. The purpose of 
regular medical care is to improve your health. The purpose of a research study is to gather 
information.
When reading this form, please note that the words “you” and “your” refer to the person 
or child (persons under 18 years of age) participating in the study rather than to a 
parent/guardian who might sign this form on behalf of the person in the study.
WHAT IS THIS STUDY ABOUT?
You are being invited to participate in this research study because you have warts on your skin. 
The purpose of this research study is to test the safety and effectiveness of a new 
investigational drug, A-101 45% Topical Solution, that is applied only to the skin. An 
“investigational drug” is a drug that is being tested and is not approved for use in the United 
States by the U.S. Food and Drug Administration (FDA).
In addition, this study will compare A-101 45% Topical Solution with a placebo to see if using A-
101 45% Topical Solution is better than using a placebo. The placebo is a solution that looks 
like A-101 45% Topical Solution but has no drug in it. 
It is planned that about 500 people with common skin warts will be in this study. 
Be aware that this form refers to A-101 45% Topical Solution as “study drug.”


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 2 of 13
HOW DOES A-101 45% TOPICAL SOLUTION WORK?
A-101 45% Topical Solution contains hydrogen peroxide (H2O2). Hydrogen peroxide is a simple
chemical combination of hydrogen and oxygen. H2O2 is commonly used in household products
including chlorine-free bleaches, general-purpose cleaning agents and disinfectants, hair dyes
and tooth-whitening products. In industry it is used in waste-water treatment and, at higher
concentrations (greater than 30%), in bleaching paper pulp, and textiles. In medicine H2O2 is
used at low concentrations (3%-6%) to cleanse wounds and as a topical antiseptic/disinfectant.
A-101 45% Topical Solution is being developed to remove common skin warts. This
investigational drug containing H2O2 may remove warts due to its ability to dissolve the wart.
IS THERE ANYTHING ELSE I CAN DO FOR MY WARTS?
You do not have to be in this study to get help for your warts. Some other things you may be 
able to do are:

Topical therapies such as acids (salicylic or trichloroacetic acids), available either over- 
the-counter or from a physician; cytotoxic therapies (topical podophyllin, cantharidin, 5-
fluorouracil, or bleomycin); topical immunomodulatory or immunotherapy (topical
imiquimod, intralesional candida antigen, topical squaric acid dibutyl ester)

Destruction of the warts by freezing (cryotherapy), electric current (electrosurgery), or
scraping or cutting them off
You should discuss your alternatives to participating in this research with the study doctor or 
study staff. In addition, you may discuss your options with your regular health care provider.
WHO IS PAYING FOR THIS STUDY?
A company called Aclaris Therapeutics, Inc., the sponsor of the study, is paying for this study.
<<Quorum may add site-specific conflict-of-interest language to the form based on information 
the site reports to Quorum.>>
WILL IT COST ANYTHING TO BE IN THIS STUDY?
There will be no charge to you for your participation in this study. The study drug, study-related 
procedures, and study visits will be provided at no charge to you or your insurance company.
HOW LONG WILL I BE IN THE STUDY?
If you decide to be in this study and the study doctor says you can be in the study, your 
participation will last about 5 months and includes 13 visits to the study center.
If you decide to be in this study, you will first enter the study’s screening period, which may last 
up to 13 days. If you continue your participation after the screening period, you will begin the 
study drug application period.


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 3 of 13
WHAT WILL HAPPEN DURING THIS STUDY?
If you decide to be in this study, you will have to stop any other wart therapies. This is known as 
a washout period. Your study doctor will tell you the length of any washout period needed. You 
will stop taking any of these therapies for the duration of your participation in the study.
You will be assigned by chance (like flipping a coin) to 1 of the following study groups:

A-101 Topical Solution

Placebo Solution (a solution that looks like A-101 45% Topical Solution but has no drug 
in it)
You have an equal chance of being in either of the study groups. Neither you nor the study 
doctor or study staff will be able to pick which study group you are in. You will not know and the 
study doctor or study staff will not know which study group you are in. The study doctor or study 
staff can find out if it is necessary to know for your health.
The study drug will be applied to up to 6 warts, which meet the requirement, twice a week for up 
to 8 weeks during visits 2 through 9. Participants between the ages of 12 and 17 years old will 
have their study drug applied once in the office by a parent of legal guardian in front of the study 
staff. The second application will be done at home by a parent or legal guardian as determined 
by the study doctor. Adult participants will be instructed by study staff how to self-apply study 
drug for the in-office treatment. The second application will be done at home by the participant 
as determined by the study doctor. 
Study drug will be applied to each of the selected warts for about 15 seconds. Application with 
study drug at each visit may be repeated 3 times to each selected wart.
You will be given a study diary to record your applications of study drug at home.
While you are in the study, you must:

Follow the instructions you are given.

Come to the study center for all visits with the study doctor or study staff.

Tell the study doctor or study staff about any changes in your health or the way you feel.

Tell the study doctor or study staff if you want to stop being in the study at any time.

Avoid scrubbing or irritating the warts being dosed – you may continue your regular skin 
care products.

Avoid excessive sun exposure to the warts being dosed.
What happens when I come for study visits?
After you sign this form, the study doctor or study staff will do the things listed below when you 
come in for study visits.


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 4 of 13
Visit 1 (Screening)

Demographic Questions: You will be asked to give personal information, such as your 
name, date of birth, race, etc.

Health and Medication Questions: You will be asked about your health, your medical 
history, and the medications you take.

Vital Signs: Your blood pressure, heart rate, breathing rate, temperature, height and 
weight will be measured.

Wart Assessment: Your skin will be assessed for warts. The study doctor will identify 
up to 6 common warts to be dosed with study drug. The warts will be measured.

Blood Testing:  Blood samples will be taken for routine laboratory evaluation.

Skin Type:  Your skin type will be assessed based on its shade/color.

Photography: Photographs of your dosing areas (of the selected warts and nearby skin) 
will be taken throughout the study to document the location and status of the warts. 
These photographs may be used for research purposes related to the study and for 
presentation at the FDA, at scientific meetings, for scientific publications, for general 
corporate purposes, and may be used for marketing purposes. Your identity will not be 
revealed in these photographs. For example, if you have a distinctive birthmark or tattoo 
that is included in the photograph, the sponsor will take measures to digitally blur that 
feature from the photographs. If you decline to have these pictures taken, you will not be 
allowed to participate in this study.

Subject Instruction Sheet:  You will be given a written instruction sheet.
Visit 2/ Day 1

Health and Medication Questions: You will be asked about any changes to your health 
or medications.

Wart Assessment: The common warts identified at Visit 1 will be looked at and 
measured by the study doctor.

Review of Inclusion and Exclusion Criteria: The study doctor will confirm that you 
continue to meet all inclusion and no exclusion criteria.

Photography: The warts will be photographed before study drug application.

Study Drug Application: Study drug will be applied to the common warts identified by 
the study doctor.

Evaluation of Application Area: The areas where study drug is applied will be 
examined for local skin reactions before study drug application. You will be asked about 
any stinging/burning or itching in those areas before study drug application.

Subject Instruction Sheet:  Your study instructions will be reviewed with you.
Visits 3 (Day 8), 4 (Day 15), Visit 5 (Day 22), Visit 6 (Day 29), Visit 7 (Day 36), and Visit 8 
(Day 43)

Health and Medication Questions: You will be asked about any changes to your health 
or medications.


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 5 of 13

Wart Assessment:  The common warts will be looked at and measured by your study 
doctor.

Photography:  The common warts will be photographed at visit 4 and visit 6 only.

Study Drug Application: Study drug will be applied to common warts during the in-
office visit as determined by the study doctor. The second weekly application of drug 
may be done home if the study doctor thinks you need another application.

Evaluation of Application Area: The areas where study drug is applied will be 
examined for local skin reactions before study drug application. You will be asked about 
any stinging/burning or itching in those areas before study drug application, if applicable.

Subject Instruction Sheet:  Your study instructions will be reviewed with you.
Visit 9/Day 50 (End of Dosing)

Health and Medication Questions: You will be asked about any changes to your health 
or medications.

Vital Signs: Your blood pressure, heart rate, breathing rate, and temperature will be 
measured.

Wart Assessment:  The common warts will be looked and measured by the study 
doctor.

Photography:  The common warts will be photographed.

Study Drug Application: Study drug will be applied to common warts during the in-
office visit as determined by the study doctor. The second weekly application of study 
drug may be done at home if the study doctor thinks you need another application.

Evaluation of Application Area: The areas where study drug is applied will be 
examined for local skin reactions before study drug application. You will be asked about 
any stinging/burning or itching in those areas before study drug application, if applicable.

Subject Instruction Sheet: Your study instructions will be reviewed with you.
Visits 10 (Day 60), 11 (Day 78), and 12 (Day 106) - Follow-up Visits

Health and Medication Questions: You will be asked about any changes to your health 
or medications.

Photography:  The common warts will be photographed at Visit 10, Visit 11, & Visit 12.

Wart Assessment:  The common warts will be looked at and measured by the study 
doctor.

Evaluation of Application Area: The areas where study drug was applied will be 
examined for local skin reactions. You will be asked about any stinging/burning or itching 
in those areas.

Subject Instruction Sheet: Your study instructions will be reviewed with you.
Visit 13 – End of Study

Vital Signs: Your blood pressure, heart rate, breathing rate, and temperature will be 
measured.


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 6 of 13

Blood Testing:  Blood samples will be taken for routine laboratory evaluation.

Photography:  The common warts will be photographed.

Wart Assessment:  The common warts will be looked at and measured by the study 
doctor.

Evaluation of Application Area: The areas where study drug was applied will be 
examined for local skin reactions. You will be asked about any stinging/burning or itching 
in those areas.
Early Discontinuation Visit
If you decide you do not want to be in the study anymore for any reason, the procedures for 
Visit 13 will be completed.
WILL BEING IN THIS STUDY HELP ME?
The study drug may help your warts, but there is no guarantee that being in this study will help 
you. Your warts might not get better or may even get worse while you are in this study. You may 
get placebo, which has no drug in it. Information from this study might help researchers come 
up with medications to help others in the future.
WHAT ARE THE RISKS TO ME IF I AM IN THIS STUDY?
Ask the study doctor if you have questions about the signs or symptoms of any side effects that 
you read about in this consent form. Hydrogen peroxide has been used in people for other 
reasons, and when it is applied topically the common adverse effects include:

Temporary discomfort in the dosing area (burning, stinging and/or itching)

Temporary redness in the dosing area

Temporary and reversible whitening (NOT BLEACHING) of the skin

Blistering

Bleaching of the hair within the dosing area.
In a previous study of subjects using hydrogen peroxide the side effects seen included:

Stinging or burning sensation at the study drug application site

Mild discomfort at the site
While not a side effect, H2O2 may bleach clothing that overlies the application area or comes in 
contact with the study drug.
Precaution: The study drug is a high-strength hydrogen peroxide product. High strength 
hydrogen peroxide products may cause serious harm or death if ingested. High strength 
hydrogen peroxide products are highly corrosive, and the FDA considers the substance to be 
dangerous. A-101 hydrogen peroxide should only be applied topically as indicated for skin 
warts.


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 7 of 13
It is possible that using A-101 may change how your regular medications, vaccines, or 
supplements work. It is very important that you tell the study doctor about any medications, 
supplements, or vaccines before you take them during the study.
Please tell the study doctor or study staff right away if you have any side effects. Please tell 
them if you have any other problems with your health or the way you feel during the study, 
whether or not you think these problems are related to the study drug.
If you feel that A-101 45% topical solution has come in contact with your eyes, mouth or nose, 
tell your study doctor immediately. Serious eye problems may happen if the solution gets into 
your eyes. Eye problems may include, pain, swelling, redness, irritation and in some cases, 
blindness.
Could I have an allergic reaction?
All topical drugs have a potential risk of an allergic reaction, which could result in a rash (red or 
rough skin) or a worse skin reaction at the area of application.
What if I am using placebo instead of A-101 during the study?
Some people in the study will get placebo instead of A-101 45% hydrogen peroxide. Placebo is 
a substance that looks like A-101 topical solution but has no hydrogen peroxide in it. If you use 
placebo during the study, it is possible that your warts may get worse. Please ask the study 
doctor or study staff if you have any questions about placebo.
If I stop my regular medication, therapy, or supplements what are the risks?
If you stop your regular medication, therapy, or supplements to be in the study, your warts 
symptoms might come back or get worse. Please tell the study doctor or study staff right away if 
you have any problems when you stop or change your regular medication, therapy, or 
supplements.
What are the risks of giving blood for this study?
The study doctor or study staff will take your blood by sticking a needle in your arm. Some 
problems you might have from this are:

pain

bruising

dizziness

infection


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 8 of 13
Unknown risks
It is possible that you could have problems and side effects of A-101 topical solution that 
nobody knows about yet, which could include your warts getting worse.
Loss of confidentiality
There is a risk of loss of confidentiality of your information. You will read more about the 
protection of your information later in this form. Please ask the study doctor or study staff if you 
would like to know more about how your information will be protected while you are in this study.
WILL I RECEIVE ANY NEW INFORMATION DURING THE STUDY?
If the study doctor or study staff learns any new information that might change your mind about 
continuing in the study, the study doctor or study staff will tell you about it.
WHAT IF I GET HURT OR SICK WHILE I AM IN THIS STUDY?
If, during the course of this study, any injury occurs to you as a direct result of the administration 
of the study drug or properly performed procedures, the Sponsor agrees to pay all medical 
expenses necessary to treat such injury: 1) to the extent you are not otherwise reimbursed by 
medical insurance; 2) provided you have followed the directions of the study doctor. 
Compensation for any injury which occurs to you as a direct result of the administration of the 
study drug or poorly performed procedures by the study doctor or study staff, will be paid after 
the Sponsor receives all appropriate documentation and completes its review, to its satisfaction, 
of all documentation regarding your claim for injury.
You will not lose any of your legal rights or release the Sponsor, the study doctor, the study 
staff, or study site from liability for negligence or intentional misconduct by signing this consent 
form.
There are no plans to provide financial compensation for such things as lost wages, disability or 
discomfort due to injury. 
Be aware that your health care payer/insurer might not cover the costs of study-related injuries 
or illnesses.
WILL I RECEIVE PAYMENT?
<<Quorum will add site-specific compensation language to the form based on information the 
site reports to Quorum.>>
DO I HAVE TO BE IN THIS STUDY?
Your participation in this study is voluntary. You can decide not to be in the study and you can 
change your mind about being in the study at any time. There will be no penalty to you, and you 


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 9 of 13
won’t lose any benefits you are entitled to. If you want to stop being in the study, tell the study 
doctor or study staff.
The study doctor or study staff or sponsor can remove you from the study at any time, even if 
you want to stay in the study.  This could happen if:

The study doctor or study staff believes it is best for you to stop being in the study.

You do not follow directions about the study.

The sponsor stops the study for any reason.
If you stop being in the study early, the study doctor or study staff may ask you some questions 
about being in the study. The study doctor or study staff may ask you to participate in some 
procedures or tests to help you leave the study safely and/or to collect more information for the 
study. If you leave the study, the study doctor and study staff will still be able to use your 
information that they have already collected.
HOW WILL MY INFORMATION BE KEPT CONFIDENTIAL?
Your identity will be protected as required by law and according to any policies the study center 
or sponsor may have. Be aware that your study records (which include your medical records, 
your signed consent form, and other information) will be shared as needed for the study. For 
example, the U.S. Food and Drug Administration (FDA), Aclaris Therapeutics, Inc. and Quorum 
Review (a group of people who review research studies to protect the rights and welfare of 
research participants) may look at your study and medical records.
Your blood samples will not be labeled with your name or other directly identifying information. 
Your samples will have a code instead. The list that matches the code with your name will be 
stored separately from your samples. Your samples will be kept only until we are able to 
complete the tests described in this form, and then your samples will be destroyed. If you 
change your mind later, be aware that your samples may or may not be withdrawn from the 
research, depending on the sponsor’s policies. You can ask the study doctor or study staff 
about this. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time.
WHO CAN I TALK TO ABOUT THIS STUDY?
In the event of an emergency, dial 911 immediately.
If you require emergency care, be sure to tell the emergency care provider about your 
participation in this study.  Contact the study doctor or study staff as soon as possible.
You can ask questions about the study at any time. You can call the study doctor or study staff 
at any time if you have any concerns or complaints. You should call the study doctor or study 
staff at the phone number listed on page 1 of this form if you have questions about the study 
procedures, study payment, or if you get hurt or sick during the study.


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 10 of 13
Quorum Review reviewed this study. Quorum Review is a group of people who review research 
studies to protect the rights and welfare of research participants. Review by Quorum Review 
does not mean that the study is without risks. If you have questions about your rights as a 
research participant, if you are not able to resolve your concerns with the study doctor or study 
staff, if you have a complaint, or if you have general questions about what it means to be in a 
research study, you can call Quorum Review or visit the Quorum Review website at 
www.QuorumReview.com.
Quorum Review is located in Seattle, Washington.
Office hours are 8:00 AM to 5:00 PM Pacific Time, Monday through Friday. Ask to speak 
with a Research Participant Liaison at 888-776-9115 (toll free).
HOW WILL MY INFORMATION BE USED AND SHARED FOR THIS STUDY?
This section explains who will use and share your health information if you agree to be in this 
study. You must authorize this use and sharing of your information by signing this form or you 
cannot be in the study.
The study doctor and study staff will collect, use, and share health information about you, 
including any information needed to do the study and other identifying information about you, 
such as your name, address, phone number, or social security number. The information used 
and shared will include:

information from your medical records

information collected about you during the research including study visits, progress 
notes, tests, procedures, photographs, etc.
Your information may be used and shared with these people for the following purposes:

The study doctor and study staff to conduct this research.

The sponsor, Aclaris Therapeutics, Inc.; people who work with or for the sponsor; and 
other researchers involved in this study. These people will use your information to review 
the study, to check the safety and results of the study, and to seek government approval 
of A-101 45% Topical Solution.

Others required by law to review the quality and safety of research, including the FDA, 
Department of Health and Human Services, Office for Human Research Protections, 
other government agencies in the United States and other countries, and Quorum 
Review.
After your information is shared with the people and companies listed above, the law may not 
require them to protect the privacy of your information. To maintain the integrity of this research, 
you might not have access to any health information developed as part of this study until it is 
completed. At that point, you generally would have access to your health information.
You can cancel your authorization to use and share your information at any time by writing a 
letter to the study doctor. If you cancel your authorization, you will not be able to continue in the 
study. If you cancel your authorization, the study doctor and study staff will still be able to use 
and share your information that they have already collected.
This authorization to use and share your information expires in 50 years.


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 11 of 13
REGULAR DOCTOR OR SPECIALIST NOTIFICATION OPTION
For your safety, you or the study doctor should tell your regular health care provider that you are 
in this study.  This is recommended so that your primary care doctor may contact the study 
doctor if they have any concerns or questions about your care.
Please indicate below whether you want us to notify your regular doctor or your specialist 
of your participation in this study.
Yes, I want the study doctor to inform my regular doctor/specialist of my participation 
in this study:
Name of Doctor
Phone
No, I do not want the study doctor to inform my regular doctor/specialist of 
my participation in this study.
I do not have a regular doctor/specialist.
The study doctor is my regular doctor/specialist.


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 12 of 13
CONSENT
I have read this form, and I have been able to ask questions about this study. The study doctor 
or study staff has talked with me about this study. They have answered all my questions. I 
voluntarily agree to be in this study. I agree to allow the collection, use, and sharing of my 
information as described above.
By signing this form, I do not give up any of my legal rights. I will get a signed copy of this 
consent form.
Printed Name of Participant
Signature of Participant (if an Adult)
Date
<<Quorum staff: Include the following for Indiana sites:
In Indiana, you must complete the following information:  
Participant’s Street Address
Participant’s City, State, ZIP>>
If participant does not have the legal capacity to consent to his/her participation:
I am the parent/guardian of the participant named above and I consent to his/her participation 
in this research study. I also authorize the collection, use and sharing of the participant’s 
information.
Printed Name of Parent/Guardian
Signature of Parent/Guardian
Date


Information and Consent Form
For Adults and Parents/Guardians of Minor Participants 
Aclaris Therapeutics, Inc.
A-101-WART-301
Initials __________    Date __________
Version 1, dated 27-JUL-2018
Page 13 of 13
I attest that the individual providing consent had enough time to consider this information, had 
an opportunity to ask questions, and voluntarily agreed to participation in this study.
Printed Name of Person Explaining Consent
Signature of Person Explaining Consent
Date
I attest that I or my representative discussed this study with the individual providing consent.
Signature of Principal Investigator or Sub-Investigator