Clinical trial NCT03812510
Conditions: Common Wart
Keywords: common warts
Sponsor: Aclaris Therapeutics, Inc.
Start date: 2019-02-07; Completion date: 2019-12-20
Enrollment: 426 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
A Phase 3 Study of A-101 Topical Solution Applied Twice a Week in Subjects with Common Warts

Detailed description:
A Phase 3 Open Label Safety Study of A-101 Topical Solution for the Treatment of Common Warts

Arms: arm 1: Topical Solution
Interventions: intervention 1: A-101
Intervention descriptions: intervention 1: hydrogen peroxide topical solution 45%

Protocol documents:
SAP_002.pdf: 


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Statistical Analysis Plan 
  
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ........................... 3 
1. 
STUDY OBJECTIVES ................................................................................. 4 
1.1 Primary Objective ............................................................................................. 4 
1.2 Secondary Objectives ........................................................................................ 4 
2. 
STUDY DESIGN .......................................................................................... 4 
3. 
STATISTICAL METHODS .......................................................................... 9 
3.1 Analysis Populations ......................................................................................... 9 
3.2 Treatment Groups and Data Presentation .......................................................... 9 
3.3 Study Day and Period Study Day .................................................................... 10 
3.4 Baseline and Analysis Visit ............................................................................. 10 
3.5 Subject Enrollment and Disposition ................................................................ 10 
3.6 Demographics and Other Baseline Characteristics ......................................... 10 
3.7 Wart Characteristics at Study Entry and During the Study ............................. 11 
3.8 Prior and Concomitant Medications, Therapies and Procedures .................... 11 
3.9 Protocol Violations .......................................................................................... 11 
3.10 Efficacy Endpoints ........................................................................................ 11 
3.10.1 Primary Efficacy Analysis - Complete Clearance of 
All Warts ....................................................................................... 11 
3.10.2 Secondary Efficacy Analyses ....................................................... 12 
3.10.2.1 Durability of Response ................................................... 12 
3.10.2.2 Mean Per-Subject Percent Wart Cleared ........................ 12 
3.10.2.3 Complete Clearance in Subjects With a 
Single Wart at Baseline ................................................... 13 
3.10.2.4 Time to Clearance of All Warts ...................................... 13 
3.11 Safety Analyses ............................................................................................. 13 
3.11.1 Extent of Exposure ....................................................................... 13 
3.11.2 Adverse Events ............................................................................. 14 
3.11.3 Local Skin Reactions .................................................................... 14 
3.11.4 Laboratory Evaluations ................................................................ 14 
3.12 Interim Analyses ............................................................................................ 15 
3.13 Sample Size ................................................................................................... 15 
3.14 Changes in/ Clarifications to the Conduct of the Study or 
Planned Analysis ....................................................................................... 15 
4. 
STATISTICAL SOFTWARE ....................................................................... 15 
5. 
REFERENCES ............................................................................................ 15 
APPENDIX A:  ASSIGNMENT TO ANALYSIS VISIT..................................... 16 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
 
Abbreviation 
Term 
AE 
Adverse Event 
CBC 
Complete Blood Count 
CRF 
Case Report Form 
ID 
Identification 
ITT 
Intent to Treat 
LSR 
Local Skin Reaction 
MedDRA 
Medical Dictionary for Regulatory Activities 
PT 
Preferred Term 
PWA 
Physician’s Wart Assessment 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Alan 
SOC 
System Organ Class 


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Statistical Analysis Plan 
  
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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-303, Version 3 
(14February2019). 
1. 
STUDY OBJECTIVES 
1.1 Primary Objective 
The primary objective of this study is to evaluate the long-term safety of A-101 45% 
when applied twice weekly to common warts. 
1.2 Secondary Objectives 
The secondary objectives of this study include: 
• 
Efficacy of A-101 45% in the treatment of recurrent and/or further 
treatments for new warts. 
• 
Duration of response to A-101 45%. 
• 
Onset of action of A-101 45%. 
2. 
STUDY DESIGN 
This is a Phase 3, open-label, long-term safety study of A-101 45% Topical 
Solution in subjects with common warts.  
In order to be eligible for A-101-WART-303, subjects must have completed 
protocol treatment on either the A-101-WART-301 or A-101-WART-302 
study.   
Subjects that have complete clearance of all warts at the end of A-101-
WART-301 or A-101-WART 302 may enter into the A-101-WART-303 
study following completion of the Visit 1 assessments.  These subjects will 
be followed every 6 weeks to assess for a recurrence or development of 
new common warts.  If a recurrence occurs or a new wart develops these 
subjects may return to the investigational site to receive A-101 45% 
Topical Solution twice a week for an additional 8 weeks.      
Subjects that have warts that have not cleared (or were not treated) at the 
completion of A-101WART-301 or A-101-WART-302 may enter into the 
A-101-WART-303 study following completion of the Visit 1 assessments 
will receive A-101 45% Topical Solution twice a week for 8 weeks. 
Subjects may continue to receive A-101 45% Topical Solution twice a 
week for 8 weeks if their warts are not clear at the end of the 8-week 
treatment period but the 8 weekly treatments must be initiated by Day 122. 
Visit 1 of A-101-WART-303 can be the same day as Visit 13 of either A-101-
WART-301 or A101-WART-302. 
All subjects will be required to remain on study for a total of 6 months. 


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Statistical Analysis Plan 
  
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During the study, the investigator may identify from 1 to 6 common warts to 
be treated twice a week for up to 8 weeks (maximum of 16 treatment 
applications).  An 8-week treatment course may be repeated. 
Figure 1 below provides a graphical representation for treatment in this 
study. 
Figure 1: WART 303 Study Diagram for Treatment 
 
 
 
Table 2 and Table 3 provide complete list of protocol required study assessments.  
 


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Table 2: Study Procedures for Subjects with Common Warts at Visit 1  
Visit   
V1  
V2  
V3  
V4  
V5  
V6  
V7  
V8  
Visit Day  
Day 1  
Day 15  
Day 29  
Day 43  
Day 60  
Day 102  
Day 144  
Day 182  
Visit Windows  
  
+3 Days  
+ 3 Days  
+ 3 Days  
+ 3 Days  
+ 3 Days  
+ 3 Days  
+ 2 Days  
In Office Visit  
▲1  
  
▲  
  
▲  
  
  
▲  
Phone Call  
  
▲4  
  
▲4  
  
▲4  
▲4  
  
Informed Consent  
▲  
  
  
  
  
  
  
  
Inclusion Criteria/Exclusion Criteria  
▲  
  
  
  
  
  
  
  
Clinical Chem / CBC2  
  
  
  
  
  
  
  
▲  
Common Wart Identification  
▲3  
  
  
  
  
  
  
  
Common Wart Dimensions   
▲  
  
▲  
  
▲  
  
  
▲  
Physician’s Wart Assessment  
▲  
  
▲  
  
▲  
  
  
▲  
Local Skin Reactions  
▲  
  
▲  
  
▲  
  
  
▲  


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Visit   
V1  
V2  
V3  
V4  
V5  
V6  
V7  
V8  
Study Medication Application5   
▲  
▲  
▲  
▲  
  
  
  
  
Study Medication Dispensing and  
Instructions for at home application  
▲  
  
▲  
  
▲  
  
  
  
Concomitant therapies  
  
▲  
▲  
▲  
▲  
▲  
▲  
▲  
Adverse Events  
▲  
▲  
▲  
▲  
▲  
▲  
▲  
▲  
1 Visit 1 of A-101-WART 303 may occur on the same day as Visit 13 of A-101-WART 301 or A-101-WART 302.   
2 Subjects who do not have their Visit 1 assessment on Visit 13 of A-101-WART 301 or A-101-WART-302 will have to have a clinical chemistry and a complete 
blood count drawn and sent to the central laboratory for analysis.  A 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.   
3 Warts that are identified for treatment must meet the requirements as outlined in Section 9.1.    
4 Investigational site staff will be required to make a phone contact with the subject on Day 15, Day 43, Day 102 and Day 144 to assess for any safety issues and 
possible new concomitant medications the subject may have started taking.  In addition, subjects are to ask if they have had any new warts develop since the last 
in office visit.    
5 Subjects over the age of 18 are to apply the A-101 study medication on the following days:  Day 1, Day 4, Day 8, Day11, Day 15, Day 18, Day 22, Day 25, Day 
29, Day 32, Day 36, Day 39, Day 43, Day 46, Day50 and Day 53.  A window of +1 day is allowed.  Subject between the ages of 1-17 will have their A-101 study 
medication applied by a parent or 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.  
 


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Statistical Analysis Plan 
  
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Table 3 Safety Observation Assessments for Subjects that are Clear at Visit 1 and Remain Clear  
Visit   
V1  
V2  
V3  
V4  
V5  
Treatment Day 
Day 1 
Week 6 (Day 42) 
Week 12 (Day 84) 
Week 18 (Day 126) 
Week 26 (Day 182) 
Window 
 
+7 Days 
+7 Days 
+7 Days 
+2 Days 
In Office Visit 
▲1 
 
 
 
▲ 
Phone Call 
 
▲2 
▲2 
▲2 
 
Informed Consent 
▲ 
 
 
 
 
Inclusion Criteria/Exclusion Criteria  
▲  
  
  
  
  
Concomitant therapies  
  
▲  
▲  
▲  
▲  
Adverse Events  
▲  
▲  
▲  
▲  
▲  
1Visit 1 of A-101-WART 303 may occur on the same day as Visit 13 of A-101-WART 301 or A-101-WART 302.  
2 Investigational site staff will contact via a documented phone call on Visit 2 Day 42, Visit 3 Day 84, Visit 4 Day 126 and Visit 5 Day 182. During the phone 
calls sites are to ask the subject if they have had any new warts develop or if a wart that was previously treated has recurred.  If a subject has had a new wart 
develop or a previously treated wart has recurred, then the subject is to be scheduled for an in -office visit to start an 8-week treatment course with A-101 study 
medication.  Subjects are to be instructed to contact the investigational site as soon as they think a new wart (or a recurrence) has developed.  The 8-week 
treatment period can start no later than Day 102.  Refer to Table 2 for the 8- week treatment schedule.    


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Statistical Analysis Plan 
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3. 
STATISTICAL METHODS  
3.1 Analysis Populations 
The populations used for analyses are defined as follows: 
• All Enrolled Population: The All Enrolled population includes all subjects that 
signed informed consent. 
• Safety Population: The Safety population includes all subjects who received at 
least one application of study medication. 
Enrollment, disposition, demographics, and baseline characteristics summaries will be 
presented for All Enrolled Population. 
The Safety population will be used for both efficacy and safety analyses and summaries.    
All subjects will be included in the listings. 
3.2 Treatment Groups and Data Presentation 
This is an open-label study with only one treatment arm.  Subjects who enter the study 
with a common wart receive study medication immediately.  Subjects who enter the study 
with no common warts do not receive study medication at the start and will not be treated 
at all if they do not develop any common warts throughout the course of the study.  In 
order to be eligible for this study, subjects must have completed protocol treatment on 
either the A-101-WART-301 or A-101-WART-302 study.  Both WART-301 and WART-
302 were double-blind studies where subjects were treated with either active A-101 45% 
topical solution or vehicle solution.  To best account for all potential exposure to A-101 
45%, summaries and analyses will take into consideration both the current open-label 
treatment status as well as the randomized treatment assignment from the subject’s 
respective double-blind study.  This classification precipitates the following four 
treatment groups. 
• Open Label A-101 45%: Double-Blind A-101 45% 
• Open Label A-101 45%: Double-Blind Vehicle 
• Open Label Not Treated: Double-Blind A-101 45% 
• Open Label Not Treated: Double-Blind Vehicle 
Depending upon analysis population, data will be summarized into all or a subset of 
treatment groups indicated above.  Summaries on All Enrolled Population will display all 
four treatment groups.  Summaries on Safety Population will display only first two 
treatment groups. 
All data listings will be sorted by treatment group and subject ID.  Subject ID will 
identify site number and double-blind study subject participated prior to open label study 


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Statistical Analysis Plan 
 
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enrollment. 
3.3 Study Day and Period Study Day 
As shown in Figure 1, subjects can potentially take multiple courses of treatment 
throughout the study.  Subjects entering the study with warts will receive treatment at 
study entry as shown in Table 2.  Subjects who enter without any common warts do not 
receive study medication immediately and follow visit schedules shown in Table 3.  If 
these subjects develop any wart during the study, they will then begin a treatment 
regimen and follow the visit schedule for treated subjects.  Subjects can initiate a 
treatment regimen up to three times (cycles) throughout the course of the study up to day 
122.  To allow for comparisons referencing each treatment cycle, Study Day will be 
calculated in two ways.  Study day is defined as the relative day in the study from time of 
enrollment (first dose if treated immediately).  Period study day is defined as the relative 
day from the day of first dose within a treatment cycle. 
3.4 Baseline and Analysis Visit 
For the analysis of efficacy data, data will be assigned to an analysis visit within a 
treatment cycle based on period study day.  These analysis visits are presented in 
Appendix A.   
For subjects who are not treated, baseline values are non-missing values prior to the start 
of the study.  For treated subjects, baseline values are last non-missing values prior to 
first application of study medication.  For analysis by treatment cycle, baseline values are 
last non-missing values before the start of a treatment cycle. 
3.5 Subject Enrollment and Disposition 
The number of subjects enrolled to this study and their prior participation in double-blind 
studies will be presented by treatment status and double-blind treatment assignment.  
Study completion status and the reasons for discontinuation by major reason (lost to 
follow-up, adverse event, poor compliance etc.) will be presented for both All 
Enrolled Population and Safety Population by treatment group as defined in Section 
3.2.  
A listing will be provided of all subjects discontinued from the study after enrollment, 
broken down by previous double-blind study participated and study center, giving a 
subject identifier and the specific reason for discontinuation, and the duration of 
treatment before discontinuation.   
3.6 Demographics and Other Baseline Characteristics 
Descriptive summary statistics of demographic and other characteristics (Age, Sex, Race, 
Ethnicity, Height, Weight, and Fitzpatrick Skin Type) list characteristics inside 
parentheses) will be generated for All Enrolled Population.  The n, mean, standard 
deviation, median, minimum, and maximum and/or frequency distributions will be 
reported, as appropriate. 


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3.7 Wart Characteristics at Study Entry and During the Study 
Wart characteristics at study entry will be summarized descriptively for Enrolled Subjects. 
 Summarized variables include identification of warts, wart dimension, and location 
(Hands, Feet, Elbows, Knees, Rest of Body).  Wart Characteristics are also summarized 
during the study by treatment cycles for the Safety Population. 
3.8 Prior and Concomitant Medications, Therapies and Procedures 
Prior and concomitant medications are listed only.  The period(s) (prior, on treatment, and 
post-therapy) in which the medications were administered will be flagged.  These rules 
are explained in Data Handling and Programming Specification Document in detail.  
Medications are coded using the WHO Drug (March 2019).   
3.9 Protocol Violations 
Protocol violations will be identified prior to database lock to measure adherence to key 
aspects of the protocol (see Section 15 of the protocol for full definitions).    Specific data 
fields that will be examined to identify protocol violations include inclusion/exclusion 
criteria and prohibited prior and concomitant medications as well as all deviations 
identified by the investigator. All protocol violations will be listed. 
3.10 Efficacy Endpoints 
The primary and secondary efficacy analyses will be carried out on the Safety 
Population.  Efficacy summaries will be supported by listings.  
Primary Efficacy Endpoint: Proportion of subjects who achieve complete clearance 
(PWA-0) of all identified warts at each analysis visit window by treatment group and 
treatment cycle.   
Four secondary efficacy endpoints are: 
• 
Durability of response:  For subjects with all warts achieving a 
status of Clear (PWA=0), the number of weeks all warts remain 
clear by treatment group and treatment cycle.    
• 
Mean per-subject percent of treated warts that are Clear (PWA=0) 
at each analysis visit by treatment group and treatment cycle.     
• 
Proportion of subjects with a single wart at baseline whose wart is 
Clear (PWA=0) by analysis visit, treatment group, and treatment 
cycle. 
• 
Median time to achieve onset of Clearance (PWA=0) for all treated 
warts by treatment group and treatment cycle. 
3.10.1 Primary Efficacy Analysis - Complete Clearance of All Warts 
The primary efficacy summary will tabulate the number and percent of subjects achieve 
complete clearance (PWA=0) at each analysis visit by treatment group.  This analysis will 
also be done by treatment group and treatment cycle.  Treatment cycle start date can vary 
from subject to subject so analysis visits will be derived from period study day as 


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described in Appendix A and Section 3.3.  All efficacy analyses will be descriptive and 
there will be no formal statistical test to compare treatment groups. 
Any identified common wart for a subject that has missing PWA data will be treated as 
not clear for the purpose of the primary efficacy analysis.  A sensitivity analysis will be 
carried out using observed data. 
3.10.2 Secondary Efficacy Analyses 
3.10.2.1 
Durability of Response 
Difference in time to recurrence of wart by treatment group is summarized using 
Kaplan Meier analysis.  This analysis will be done at overall study level and by 
treatment cycle. 
 
• Overall Study Level: Time to recurrence will be presented graphically 
with a Kaplan Meier curve.  For this analysis, time to first recurrence in 
the study will only be included for each subject.  Subjects with no wart at 
the end of study will be censored.  The proportion of subjects that remain 
clear of warts at the end of the study will also be presented. 
 
• By Treatment Cycle: For this analysis, time to first recurrence in the 
treatment cycle will only be included for each subject.  Subjects with no 
wart at the end of the treatment cycle will be censored. 
 
Kaplan-Meier estimates and associated confidence intervals are obtained using SAS 
statements consistent with the following syntax: 
 
PROC LIFETEST ALPHA=.05; 
TIME DAYS*CENSOR(1); 
SURVIVAL OUT=SURV CONFTYPE=LOGLOG; 
STRATA TREATMENT GROUP; 
 
3.10.2.2 
Mean Per-Subject Percent Wart Cleared 
Mean per-subject percent of treated warts that are Clear (PWA=0) at each analysis visit 
will be summarized descriptively by treatment group and treatment cycle.  Subjects with 
non-missing PWA values are only included.  For each subject, percent of cleared warts 
are computed before summarizing across subjects in a treatment group.  Data from 
subjects who begin treatment later in the study will be included once they start treatment.  
Treatment cycle start date can vary from subject to subject. 


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3.10.2.3 
Complete Clearance in Subjects With a Single Wart at Baseline 
Proportion of subjects with a single wart at baseline whose wart is Clear (PWA=0) will be 
summarized descriptively by treatment cycle, analysis visit, and treatment group.  
Treatment cycle start date can vary from subject to subject.  Subjects with a single Wart 
in the beginning of treatment cycle and without a Wart assessment at the timepoint 
analyzed are assigned non-clearance.  
 
3.10.2.4 
Time to Clearance of All Warts 
The last secondary endpoint analyzed, the difference in time to clearance of all warts 
from start of a treatment cycle between treatment groups, is summarized using Kaplan 
Meier analysis.  Confidence intervals for clearance times are based upon the methods of 
Brookmeyer and Crowley1.  This analysis will be performed on a subject level by 
treatment cycle.  Treatment cycle start date can vary from subject to subject.  Subjects 
whose warts are not cleared at the end of a treatment cycle are censored. 
Kaplan-Meier estimates and associated confidence intervals are obtained using SAS 
statements as shown in Section 3.10.2.1. 
 
3.11 Safety Analyses 
Safety summaries will be conducted on the Safety Population. 
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 laboratory assessments and local skin reactions will be the last 
non-missing value collected before first application of A-101 45% in this study.  For most 
subjects, Visit 1 laboratory measurements in this study are done on Visit 13 of parent 
double-blind study (A-101-WART-301 or A-101-WART-302). 
3.11.1 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 total number of wart treatments performed during 
the treatment period (through date of last application to any wart) divided by the total 
number of wart treatments expected to be performed. 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). 


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3.11.2 Adverse Events 
Adverse events are coded using the MedDRA (Version 22) 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 within 30 days of each 
application of study medication). All adverse events are included in the data listings 
including those that are not considered treatment emergent.   
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 within 30 days of an application of study medication are considered 
“treatment emergent”.  Events with onset dates more than 30 days after the most recent 
application of study medication are considered as "post-therapy."  In this study, subjects 
can possibly receive medication up to three cycles and multiple doses of medication 
within a treatment cycle.  The above rule will be applied to all known doses of 
medication while determining study period. 
 
Frequency tabulations are presented by MedDRA SOC and preferred term, for all adverse 
events; study treatment-related adverse events, 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’. 
 
3.11.3 Local Skin Reactions 
The number of subjects with local skin reaction signs or symptoms that worsened by at 
least 1 grade from baseline any time after the first application of study medication will be 
tabulated by treatment group for each LSR as well any LSR. A separate summary limited 
to LSRs that worsen and which occur within 30 days of the last application of study 
medication will be provided.  Additionally, to assess effect of number of cycles of 
applications of study medication on LSR, this summary will be presented by treatment 
cycle also. 
3.11.4 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 will be summarized using descriptive statistics for 
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. 


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3.12 Interim Analyses 
No interim analyses are planned for this study. 
3.13 Sample Size 
The sample size is based on an estimate of how many subjects will be required to 
provide at least 100 subjects requiring repeated treatment for a wart over the 
course of the study.  
• 
By recruiting 400 subjects, we estimate 200 subjects will have received 
active treatment in the A101-WART 301/302 studies.  
• 
We expected approximately 26% of warts treated in A-101-WART-
301/302 studies to be clear at the end of the A-101-WART-301/302 
studies.  
• 
Based on the assumption that 26% of warts will be clear, at least 148 
subjects will require exposure to active treatment.  
• 
We anticipate that some subjects originally randomized to vehicle (in 
double-blind studies) will be exposed to active treatment. 
As a result, the study should exceed the target of exposing more than 100 subjects 
to repeated treatments over the course of the study. 
3.14 Changes in/ Clarifications to the Conduct of the Study or Planned Analysis 
Originally, both efficacy (primary and secondary endpoints) and safety analyses were 
planned on intent to treat (ITT) population.  The primary objective of the study is to 
evaluate long-term safety of A-101 45% when applied twice weekly to common warts.  
Considering this and the fact that all treated subjects will administer the same medication 
(A-101 45%), it was deemed more appropriate to conduct both efficacy and safety 
analyses on the Safety Population.  For that reason, all analyses will be conducted on the 
Safety Population.  Data collected for subjects who did not receive treatment will be 
listed. 
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. 
 


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 APPENDIX A:  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 Treatment Period Study Day for each treatment cycle.  These analysis visits are 
based on the nominal, scheduled visits in the protocol and treatment cycle.  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 Visits Within Each Treatment Cycle: 
Analysis Visit 
Treatment Period Study Day 
Range 
Target Treatment Period Study 
Day 
Px V1 
1 
1 
Px V2 
2 - 22 
15 
Px V3 
23 - 36 
29 
Px V4 
37 – 51 
43 
Px V5 
52 – 81 
60 
Px V6 
82 – 127 
102 
Px V7 
128 – 163 
144 
EOS (End of Study) Visit 
>= 164 
182 
Note: P indicates Treatment Period (Treatment Cycle), x indicates Treatment Period 
Number (Either 1 or 2 or 3), and V indicates Visit.  There is only one EOS visit for all 
subjects. 
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.   
 

ICF_001.pdf: 
Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 1 of 14 
INFORMATION AND CONSENT FORM 
For Adults and Parents/Guardians of Minor Participants 
For California Sites 
 
Study Title: 
A Phase 3 Open Label Safety Study of A-101 Topical Solution for the Treatment 
of Common Warts 
Study #: 
A-101-WART-303 
Sponsor: 
Aclaris Therapeutics, Inc 
Study Doctor: 
<<investigator>> 
<<firm name>> 
<<street address>>, <<city>>, <<state>><<zip>> 
Telephone Number: <<000-000-0000>> 
After Office Hours:  <<000-000-0000>> 
 
Before you read this consent form, you should read a copy of the California Experimental 
Subject’s Bill of Rights.  Ask the study staff for a copy of this document if you haven’t 
already received one. 
 
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 participated in a 
prior study run by Aclaris Therapeutics called either, Thwart 1 or Thwart 2, which are studies for 
common warts. The purpose of this research study is to test the long-term safety 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). 


Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 2 of 14 
It is planned that about 400 people who have participated in either the Thwart 1 or Thwart 2 
studies will be in this study.  
Be aware that this form refers to A-101 45% Topical Solution as “study drug.” 
 
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. 
 
If I choose not to participate in this study, what are other options I have? 
You do not have to be in this study.  
If you currently have warts, or develop new 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. 
 


Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 3 of 14 
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 6 months and includes up to 4 visits to the study center. 
If you decide to be in this study, your first visit may be the same day as the last visit of the prior 
study, or your first visit may be scheduled for a different day. 
WHAT WILL HAPPEN DURING THIS STUDY? 
If you decide to be in this study and all of your warts have cleared during the prior study, you will 
be called approximately every 6 weeks to ask if you have had a previously treated wart return, 
or if you have had a new wart develop. If you develop a new wart, or have a reoccurrence of a 
previously treated wart, you do not have to wait for the study site to call you; you can call the 
study site and they will request you come in to the office. After assessing the new wart, if the 
wart or warts (up to 6) meet the requirements, they will be treated twice a week for up to 8 
weeks with A-101 45%.  
If you decide to be in this study, and you currently have common warts, you will begin treatment 
with A-101 45%.  
The study drug will be applied to up to 6 warts, which meet the requirement, twice a week for up 
to 8 weeks from Visit 1 through Day 53 (a few days before the 3rd office visit, called Visit 5). 
Participants between the ages of 12 and 17 years old will have their study drug applied by a 
parent or legal guardian. Adult participants will be instructed by study staff how to self-apply 
study drug. 
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. You will bring 
your study diary with you to each study visit.  
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. 
All subjects who sign this informed consent form who have or develop new warts or a 
reoccurrence of their previously treated warts, will be treated with A-101 45%. 
 
What happens when I come for study visits? 
After you sign this form, if you do not currently have any warts, the study doctor or study staff 
will do the following things: 


Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 4 of 14 
 
Visit 1 (In Office)  
• 
Informed Consent: You will be asked to sign this informed consent form. 
• 
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 any changes to your health 
or medications. 
 
Visit 2 
• 
A phone call: You will receive a phone call from the site staff to ask you questions 
about any changes to your health or medications, and to ask if you have had any new 
warts develop since the last time you were seen in the office. 
 
Visits 3  
• 
A phone call: You will receive a phone call from the site staff to ask you questions 
about any changes to your health or medications, and to ask if you have had any new 
warts develop since the last time you were seen in the office. 
 
Visit 4 
• 
A phone call: You will receive a phone call from the site staff to ask you questions 
about any changes to your health or medications, and to ask if you have had any new 
warts develop since the last time you were seen in the office. 
 
Visit 5 End of Study (In Office)  
• 
Health and Medication Questions: You will be asked about any changes to your health 
or medications and if you have had any new warts develop since the last time you were 
seen in the office.  
 
Early Discontinuation Visit 
If you decide you do not want to be in the study anymore for any reason, the procedures for 
Visit 5 will be completed. 
 
If you develop new warts or have a reoccurrence of any previously treated warts while you are 
being followed by phone calls, before day 102 of the study, you will be asked to come in to the 
office to have the wart or warts assessed and you will be able to begin treatment with A-101 
according to the visit schedule below.  


Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 5 of 14 
 
After you sign this form, if you currently have a wart, or warts, the study doctor or study staff will 
do the things listed below when you come in for study visits. 
Visit 1 (In Office)  
• 
Informed Consent: You will be asked to sign this informed consent form. 
• 
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 any changes to your health 
or medications. 
• 
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, if your 
visit 1 is done on a day other than the last visit day (Visit 13) of the prior study. 
• 
Subject Instruction Sheet:  You will be given a written instruction sheet that will be 
reviewed with you.  
• 
Study Medication Application: Study drug will be applied to common warts during the 
in-office visit as determined by the study doctor. If the study doctor thinks you need 
another application, they will provide you with enough applicators to do the remaining 
applications at home. 
• 
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. 
  
Visit 2 
• 
A phone call: You will receive a phone call from the site staff to ask you questions 
about any changes to your health or medications, and to ask if you have had any new 
warts develop since the last time you were seen in the office. 
 
Visits 3 (In office) 
• 
Health and Medication Questions: You will be asked about any changes to your health 
or medications. 
• 
Wart Assessment:  The common warts will be looked at and measured by your study 
doctor. 
• 
Study Drug Application: Study drug will be applied to common warts during the in-
office visit as determined by the study doctor. If the study doctor thinks you need another 
application, they will provide you with enough applicators to do the remaining 
applications at home. 
• 
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. 


Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 6 of 14 
• 
Subject Instruction Sheet:  Your study instructions will be reviewed with you, and 
additional study medication will be provided.  
 
Visit 4 
• 
A phone call: You will receive a phone call from the site staff to ask you questions 
about any changes to your health or medications, and to ask if you have had any new 
warts develop since the last time you were seen in the office. 
 
Visits 5 (In office) 
• 
Health and Medication Questions: You will be asked about any changes to your health 
or medications. 
• 
Wart Assessment:  The common warts will be looked at and measured by your 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, if applicable.  
  
Visit 6 
• 
A phone call: You will receive a phone call from the site staff to ask you questions 
about any changes to your health or medications, and to ask if you have had any new 
warts develop since the last time you were seen in the office. 
 
Visit 7 
• 
A phone call: You will receive a phone call from the site staff to ask you questions 
about any changes to your health or medications, and to ask if you have had any new 
warts develop since the last time you were seen in the office. 
 
Visit 8 – End of Study (In office) 
• 
Health and Medication Questions: You will be asked about any changes to your health 
or medications. 
• 
Blood Testing:  Blood samples will be taken for routine laboratory evaluation. 
• 
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. 
 


Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 7 of 14 
Early Discontinuation Visit 
If you decide you do not want to be in the study anymore for any reason, the procedures for 
Visit 8 will be completed. 
 
Will I need time to recover after my participation in the study?  
Ask the study doctor or study staff for the estimated recovery time of your participation in this 
study.  
 
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. 
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. 
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. 


Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 8 of 14 
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. 
 
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 
 
Unknown risks 
It is possible that you could have problems and side effects of A-101 45% 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. 
 


Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 9 of 14 
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 
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 


Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 10 of 14 
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. 
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. 
 
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  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 11 of 14 
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 


Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 12 of 14 
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. 
 
 
 
 
 
Signature of Participant (If an Adult) 
 
Date 
or Parent/Guardian 
 
 
 
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  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 13 of 14 
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 
 
 
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 
 
 
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. 
 
 


Information and Consent Form 
For Adults and Parents/Guardians of Minor Participants  
For California Sites 
Aclaris Therapeutics, Inc. 
A-101-WART-303 
 
Initials __________    Date __________ 
Version 1, dated 5-NOV-2018 
Page 14 of 14 
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 
 

Prot_000.pdf: 
Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
1 
 
 
  
 
CLINICAL STUDY PROTOCOL 
 
Protocol Number: A-101-WART-303 
 
A PHASE 3 OPEN LABEL SAFETY STUDY OF A-101 TOPICAL 
SOLUTION FOR THE TREATMENT OF COMMON WARTS 
 
Version 2:  20 December 2018 
Version 3: 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 
Ann-Marie Hulstine 
Telephone:  484-540-6362 
Cell Phone:  484-983-0045 
Email:  ahulstine@aclaristx.com 
 
 
Serious Adverse Event Facsimile:  484-324-2359 
 
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-303 
Protocol: Version 3:  14 February 2019 
 
3 
 
 
  
 
INVESTIGATOR’S AGREEMENT 
Protocol Number:  A-101-WART-303 
Protocol Title:  A Phase 3 Open Label Safety Study of A-101 Topical Solution for the 
Treatment of Common Warts 
Protocol Version 3:  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-303 
Protocol: Version 3:  14 February 2019 
 
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Protocol 
Version 
Date 
Section 
Revisions 
Version 
1 
12 October 
2018 
NA 
Original Protocol  
Version 
2 
20 
December 
2018 
Protocol Cover 
Page 
Sponsor contact information has been updated. 
 
 
Synopsis, Section 
7.1 
Added Inclusion criteria 7, identified warts must 
have a longest axis of ≤8 mm.    
 
 
Table 3, Footnote 
2 
A typo in footnote 2 was corrected.  
 
 
Section 9.1 
Added clarification that identified warts must have a 
longest axis of ≤8 mm.  Removed any minimum 
size requirements, there are no minimum size or 
thickness requirements for warts to be eligible for 
entry to this protocol. 
 
 
Table 4 
Protected from was added to the storage conditions 
for the investigational product. Additionally, the 
footnote that any excursion from the storage 
conditions must be reported to Aclaris. 
 
 
10.8 
Added a sentence to clarify that all at home 
treatment applications must be recorded on the 
subject diary. 
 
 
10.9 
Biohazard bag was changed to Ziptop bag. 
 
 
12.1 
Added clarification that subjects should remain in 
the clinic for 20 minutes after any in office 
application to ensure any local skin reactions are 
appropriately documented as adverse events. 
 
 
Appendix 1 
Revised the patient instruction sheet to simplify the 
instructions regarding the at home disposal of used 
A-101 applicators.  
 
 
 
Typos and formatting have been updated through 
out. 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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Protocol 
Version 
Date 
Section 
Revisions 
Version 
3 
14 
February 
2019 
Synopsis, 
Exclusion 7 
Section 7.2, 
Exclusion 7 
Clarified that the use of hydrogen peroxide while in 
the A-101-WART-301 or A-101-WART-302 study 
was not exclusionary.  
 
 
Table 2 
Visit 8 was updated to EOS (End of Study) the visit 
name was updated for continuity between the 
treatment groups. 
 
 
Table 2 
A footnote 6 was added to table 2 to clarify that IP 
should only be dispensed at visit 5, if the subject has 
warts that did not clear during the 8-week treatment 
cycle or if new warts have appeared. 
 
 
Table 3 
Visit 5 was updated to EOS (End of Study) the visit 
name was updated for continuity between the 
treatment groups. 
 
 
Section 9.2 
The thickness of a wart is not a measurement which 
we require to be noted for this study. 
 
 
Section 10.4 
This section was updated to note that any unused IP 
will be disposed of after final accountability has 
been performed. 
 
 
Section 13.2.2 
An update was made to this section to reflect that 
SAEs will be entered in to the Axiom database 
rather than requiring SAEs to be faxed in. 
 
 
Section 14 
The statistics section has been updated to reflect the 
statistical analyses that will be completed for the 
study. 
 
 
Section 7.6 
Updated the language on subject numbering to 
clarify that subjects will retain the subject number 
from the parent study.  
 
 
Throughout 
Formatting has been updated throughout. 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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1. 
SYNOPSIS 
Protocol Number A-101-WART-303 Synopsis 
Protocol Number:  
A-101-WART 303  
A Phase 3 Open Label Safety Study of A-101 Topical Solution for 
the Treatment of 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).     
Study Objectives: 
 
Primary: 
The primary objective of this study is to evaluate the long-term safety of A-101 45% when 
applied twice weekly to common warts.  
 
Secondary: 
The secondary objectives of this study include: 
• Efficacy of A-101 45% in the treatment of recurrent and/or further treatments for new 
warts 
• Duration of response of A-101 45%  
• Onset of action of A-101 45%  
Study Design:   
This is a phase 3, open label, long term safety study of A-101 Topical Solution 45% in 
subjects with common warts. 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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In order to be eligible for A-101-WART-303, subjects must have completed protocol 
treatment on either the A-101-WART-301 or A-101-WART-302 study.  
Subjects that have complete clearance of all warts at the end of A-101-WART-301 or A-101-
WART 302 may enter into the A-101-WART-303 study following completion of the Visit 1 
assessments.  These subjects will be followed every 6 weeks to assess for a recurrence or 
development of new common warts.  If a recurrence occurs or a new wart develops these 
subjects may return to the investigational site to receive A-101 Topical Solution 45% twice a 
week for an additional 8 weeks.     
Subjects that have warts that have not cleared at the completion of A-101-WART-301 or A-
101-WART 302 may enter into the A-101-WART-303 study following completion of the Visit 
1 assessments and will receive A-101 Topical Solution 45% twice a week for 8 weeks.  If at 
the completion of the initial 8-week treatment course with A-101 Topical Solution 45% the 
identified warts are not clear, subjects may continue to receive repeated 8-week treatment 
course with A-101 Topical Solution 45% twice a week. The final 8-week treatment course 
must be initiated by Day 122.   
 
Safety will be evaluated based on clinical laboratory studies (hematology and clinical 
chemistry), assessment of local skin reactions (LSRs), assessment of adverse events (AEs), 
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.  
 
Number of Patients to be Enrolled: 
Approximately 400 subjects will be enrolled to the study.   
Number of Study Sites: 
This study will be conducted in the US only at approximately 50 treatment centers.   
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. Subject must have completed study participation in either A-101-WART 301 or A-
101-WART 302.  
3. Male or female ≥ 1 year old.  


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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4. Subject has or has had a clinical diagnosis of common warts (verruca vulgaris). 
5. 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.   
6. Subject is willing and able to follow all study instructions and to attend all study visits. 
7. Identified warts must have a longest axis of ≤8 mm.    
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.). 
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 (other than IP from the 301/302 study) 
• Antimetabolite therapy (e.g., 5-fluorouracil); 8 weeks 
• Retinoids; 90 days 
• Over-the-counter (OTC) wart therapies and cantharidin; 28 days 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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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 (other than the 
Aclaris 301 or 302 study) in which administration of an investigational treatment 
occurred within 30 days prior to Visit 1.  
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 anticipated time for study enrollment is approximately 3 months. The duration of study 
participation is a maximum of 184 days per subject.  The maximum anticipated duration for 
the study is approximately 9 months. 
 
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, concomitant 
medications, as well as through the assessment of local skin reactions, and skin examinations.   
 
Study Drug Administration 
Subjects with identified common warts (up to 6) will apply the A-101 Topical Solution 45% to 
each identified common wart which meets the requirements for treatment twice a week for up 
to 8 weeks per treatment (maximum of 16 applications).  Eight week treatment courses may be 
repeated.      


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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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 should 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-303 
Protocol: Version 3:  14 February 2019 
 
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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
1. 
SYNOPSIS ...................................................................................................................6 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............11 
TABLE OF CONTENTS ...............................................................................................................11 
LIST OF TABLES .........................................................................................................................14 
LIST OF FIGURES .......................................................................................................................15 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................16 
4. 
INTRODUCTION ......................................................................................................18 
4.1. 
Summary .....................................................................................................................18 
4.2. 
Study Rationale ...........................................................................................................19 
5. 
OBJECTIVES .............................................................................................................21 
5.1. 
Study Objectives .........................................................................................................21 
5.1.1. 
Primary Objective .......................................................................................................21 
5.1.2. 
Secondary Objectives .................................................................................................21 
6. 
STUDY DESIGN .......................................................................................................22 
6.1. 
Number of Subjects and Study Centers ......................................................................23 
6.2. 
Duration of Study .......................................................................................................23 
7. 
STUDY ENTRY CRITERIA .....................................................................................24 
7.1. 
Inclusion Criteria ........................................................................................................24 
7.2. 
Exclusion Criteria .......................................................................................................24 
7.3. 
Removal of Subjects from Study Therapy ..................................................................25 
7.4. 
Withdrawal Procedures ...............................................................................................26 
7.5. 
Subject Replacement ..................................................................................................26 
7.6. 
Subject Identifier (SI) .................................................................................................26 
8. 
STUDY PROCEDURES ............................................................................................27 
9. 
STUDY ASSESSMENTS ..........................................................................................31 
9.1. 
Identification of Common Warts ................................................................................31 
9.2. 
Common Wart Dimensions and Physician’s Wart Assessment (PWA) .....................31 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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9.3. 
Phone Call Visits ........................................................................................................32 
10. 
STUDY TREATMENT ..............................................................................................33 
10.1. 
Investigational Study Medication ...............................................................................33 
10.2. 
Subject Randomization ...............................................................................................33 
10.3. 
Study medication packaging, storage, and dispensing ...............................................33 
10.4. 
Drug Accountability ...................................................................................................34 
10.5. 
Study Medication Treatment ......................................................................................34 
10.6. 
Preparing the Study Medication for Application ........................................................35 
10.7. 
Applying Study Medication ........................................................................................37 
10.8. 
Subject Instructions ....................................................................................................37 
10.9. 
Other Study Supplies ..................................................................................................38 
10.10. 
Dose Modification ......................................................................................................39 
10.11. 
Breaking the Blind ......................................................................................................39 
11. 
PREVIOUS AND CONCOMITANT THERAPIES ..................................................40 
11.1. 
Previous Therapy ........................................................................................................40 
11.2. 
Concomitant Therapies ...............................................................................................40 
11.3. 
Prohibited Therapies ...................................................................................................41 
12. 
ASSESMENT OF SAFETY .......................................................................................42 
12.1. 
Local Skin Reactions (LSRs)......................................................................................42 
12.2. 
Clinical Laboratory Sampling.....................................................................................44 
13. 
ADVERSE EVENTS..................................................................................................46 
13.1. 
Definitions ..................................................................................................................46 
13.1.1. 
Adverse Events (AEs) .................................................................................................46 
13.1.2. 
Serious Adverse Events (SAEs) .................................................................................47 
13.1.3. 
Adverse Event Reporting Period ................................................................................47 
13.1.4. 
Severity .......................................................................................................................47 
13.1.5. 
Relationship to Study Medication ..............................................................................48 
13.2. 
Reporting Procedures ..................................................................................................48 
13.2.1. 
Procedures for Reporting Adverse Events ..................................................................48 
13.2.2. 
Procedure for Reporting Serious Adverse Events ......................................................49 
13.2.3. 
Withdrawal Due to an Adverse Event ........................................................................49 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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14. 
STATISTICAL CONSIDERATIONS .......................................................................50 
14.1. 
Sample Size and Power Considerations .....................................................................50 
14.2. 
Analysis Populations ..................................................................................................50 
14.3. 
Statistical Analysis of Efficacy ...................................................................................50 
14.4. 
Statistical Analysis of Safety Data .............................................................................51 
14.5. 
Interim Analysis ..........................................................................................................52 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................53 
15.1. 
Protocol Amendments ................................................................................................53 
15.2. 
Protocol Violations .....................................................................................................53 
15.3. 
Training .......................................................................................................................53 
15.4. 
Monitoring ..................................................................................................................53 
15.5. 
Data Management .......................................................................................................54 
15.6. 
Quality Assurance .......................................................................................................54 
15.7. 
Record Retention ........................................................................................................54 
16. 
ETHICS AND GENERAL STUDY CONDUCT CONSIDERATIONS ...................56 
16.1. 
Institutional Review Board (IRB)/Ethics Committee (EC) ........................................56 
16.2. 
Ethical Conduct of the Study ......................................................................................57 
16.3. 
Regulatory Documents ...............................................................................................57 
16.4. 
Contractual Requirements ..........................................................................................57 
17. 
REFERENCES ...........................................................................................................58 
APPENDIX 1. A-101-WART-303 SUBJECT INSTRUCTION SHEET FOR 
IDENTIFIED WARTS TO BE TREATED ...............................................................59 
APPENDIX 2. PWA SITE USER MANUAL ............................................................................63 
 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................16 
Table 2: 
Study Procedures for Subjects with Common Warts at Visit 1 ..................................28 
Table 3 Safety Observation Assessments for Subjects that are Clear at Visit 1 and 
Remain Clear ..............................................................................................................29 
Table 4: 
Study Medication Information ....................................................................................33 
 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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LIST OF FIGURES 
Figure 1 WART 303 Study Diagram for Treatment ......................................................................23 
Figure 2: 
Diagram Showing the Process for Preparing A-101 Study Medication .....................36 
 
  


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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3. 
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 
H2O2 
Hydrogen Peroxide 
ICF 
Informed Consent Form 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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Abbreviation  
Term 
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 
US 
United States 
w/w 
Weight-to-weight 
 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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4. 
INTRODUCTION 
4.1. 
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 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. 


Aclaris Therapeutics, Inc. 
 
 
Protocol Number:  A-101-WART-303 
Protocol: Version 3:  14 February 2019 
 
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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. 
 
4.2. 
Study Rationale 
The rationale for the dose selection and treatment design of A-101-WART 301 and 
A-101-WART-302 and this open label, long term safety study is based on data 
collected from three completed (3) Phase 2 studies which assessed dose response 
and dose frequency of A-101 (H2O2) Topical Solution in patients with common 
warts.  All three studies demonstrated good efficacy and safety of H2O2  45% for the 
treatment of common warts.   
The three studies conducted are identified below and they represent data collected 
from 406 subjects. 
• 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)  


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On the basis of these successful Phase II studies, Aclaris has progressed to phase III with studies 
A-101-WART 301 and A-101-WART-302.  These studies will assess efficacy and safety of 8 
weeks of treatment and 12 weeks of post treatment follow up.  Aclaris recognizes that many 
patients may require multiple treatment courses and there is therefore a need to assess the long- 
term safety of topical H2O2 45%.  A-101-WART-303 is therefore designed to assess the long-term 
safety of patients who were initially treated in studies A-101-WART-301 and A-101-WART-302. 


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Protocol Number:  A-101-WART-303 
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5. 
OBJECTIVES 
5.1. 
Study Objectives 
5.1.1. 
Primary Objective 
The primary objective of this study is to evaluate the long-term safety of A-101 45% when 
applied twice weekly to common warts. 
5.1.2. 
Secondary Objectives 
The secondary objectives of this study include: 
• Efficacy of A-101 45% in the treatment of recurrent and/or further treatments for new 
warts  
• Duration of response of A-101 45%  
• Onset of action of A-101 45%  


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6. 
STUDY DESIGN 
This is a phase 3, open label, long term safety study of A-101 Topical Solution 45% in subjects 
with common warts. 
In order to be eligible for A-101-WART-303, subjects must have completed protocol treatment 
on either the A-101-WART-301 or A-101-WART-302 study.  
Subjects that have complete clearance of all warts at the end of A-101-WART-301 or A-101-
WART 302 may enter into the A-101-WART-303 study following completion of the Visit 1 
assessments.  These subjects will be followed every 6 weeks to assess for a recurrence or 
development of new common warts.  If a recurrence occurs or a new wart develops these 
subjects may return to the investigational site to receive A-101 Topical Solution 45% twice a 
week for an additional 8 weeks.     
Subjects that have warts that have not cleared (or were not treated) at the completion of A-101-
WART-301 or A-101-WART 302 may enter into the A-101-WART-303 study following 
completion of the Visit 1 assessments will receive A-101 Topical Solution 45% twice a week for 
8 weeks. Subjects may continue to receive A-101 Topical Solution 45% twice a week for 8 
weeks if their warts are not clear at the end of the 8-week treatment period but the 8 weekly 
treatments must be initiated by Day 122.   
Visit 1 of A-101-WART-303 can be the same day as Visit 13 of either A-101-WART-301 or A-
101-WART 302.   
All subjects will be required to remain on study for a total of 6 months.   
During the study, the investigator may identify from 1 to 6 common warts (during a 8 week 
treatment period) to be treated twice a week for up to 8 weeks (maximum of 16 treatment 
applications).  An 8-week treatment course may be repeated.   
Refer to Table 2 and Table 3   and  for a complete list of protocol required study assessments. 
 


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Figure 1 WART 303 Study Diagram for Treatment 
6.1. 
Number of Subjects and Study Centers 
Approximately 400 subjects will be enrolled to the study at approximately 50 investigational 
centers in the US.   
6.2. 
Duration of Study 
The anticipated time for study enrollment is approximately 3 months. The duration of study 
participation is a maximum of 184 days per subject.  The maximum anticipated duration for the 
study is approximately 9 months. 


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Protocol: Version 3:  14 February 2019 
 
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7. 
STUDY ENTRY CRITERIA 
7.1. 
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. Subject must have completed study participation in either A-101-WART 301 or A-101-
WART 302.  
3. Male or female ≥ 1 year old.  
4. Subject has or has had a clinical diagnosis of common warts (verruca vulgaris). 
5. 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.   
6. Subject is willing and able to follow all study instructions and to attend all study visits.  
7. Identified warts must have a longest axis of ≤8 mm.    
7.2. 
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 
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: 


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• 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 (other than IP from the 301/302 study) 
• 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 (other than the 
Aclaris 301 or 302 study) 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.   
7.3. 
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 
• 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. 
 
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.   
 


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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 
7.4. 
Withdrawal Procedures 
If a subject withdraws from the study prior to Day 182 (6-month time-point), the reason for 
withdrawal 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. 
7.5. 
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.   
7.6. 
Subject Identifier (SI) 
The investigator or designee will assign a unique eight-digit subject identifier (SI) to each subject 
at Visit 1. 
The SI format will be NNN-NN-NNN where the first 3 digits associate the subject with either the 
301 or 302 study, the middle 2 digits are the investigational center site number (using leading 
zeroes, as appropriate) and the final 3 digits are the subject number which was assigned during 
the parent study.  For example, the SI for the second subject previously treated on the A-101-
WART-301 study that signs an informed consent at site number 04 would be 301- 04-002. 
The subject will be identified using the SI in all study documentation for the duration of the 
study. 
 


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8. 
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 and Table 3 .  A written, signed informed consent form (ICF) must be 
obtained from each subject prior to performing any study related procedure. 


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 Table 2: 
Study Procedures for Subjects with Common Warts at Visit 1 
Visit  
V1 
V2 
V3 
V4 
V5 
V6 
V7 
EOS 
Visit Day 
Day 1 
Day 15 
Day 29 
Day 43 
Day 60 
Day 102 
Day 144 
Day 182 
Visit Windows 
 
+3 Days 
+ 3 Days 
+ 3 Days 
+ 3 Days 
+ 3 Days 
+ 3 Days 
+ 2 Days 
In Office Visit 
▲1 
 
▲ 
 
▲ 
 
 
▲ 
Phone Call 
 
▲4 
 
▲4 
 
▲4 
▲4 
 
Informed Consent 
▲ 
 
 
 
 
 
 
 
Inclusion Criteria/Exclusion Criteria 
▲ 
 
 
 
 
 
 
 
Clinical Chem / CBC2 
 
 
 
 
 
 
 
▲ 
Common Wart Identification 
▲3 
 
 
 
 
 
 
 
Common Wart Dimensions  
▲ 
 
▲ 
 
▲ 
 
 
▲ 
Physician’s Wart Assessment 
▲ 
 
▲ 
 
▲ 
 
 
▲ 
Local Skin Reactions 
▲ 
 
▲ 
 
▲ 
 
 
▲ 
Study Medication Application5  
▲ 
▲ 
▲ 
▲ 
 
 
 
 
Study Medication Dispensing and 
Instructions for at home application 
▲ 
 
▲ 
 
▲6 
 
 
 


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Visit  
V1 
V2 
V3 
V4 
V5 
V6 
V7 
EOS 
Concomitant therapies 
 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Adverse Events 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
1Visit 1 of A-101-WART 303 may occur on the same day as Visit 13 of A-101-WART 301 or A-101-WART 302.  
2 Subjects who do not have their Visit 1 assessment on Visit 13 of A-101-WART 301 or A-101-WART-302 will have to have a clinical chemistry and a complete 
blood count drawn and sent to the central laboratory for analysis.  A 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.  
3 Warts that are identified for treatment must meet the requirements as outlined in Section 9.1.   
4 Investigational site staff will be required to make a phone contact with the subject on Day 15, Day 43, Day 102 and Day 144 to assess for any safety issues and 
possible new concomitant medications the subject may have started taking.  In addition, subjects are to ask if they have had any new warts develop since the last 
in office visit.   
5 Subjects over the age of 18 are to apply the A-101 study medication on the following days:  Day 1, Day 4, Day 8, Day11, Day 15, Day 18, Day 22, Day 25, Day 
29, Day 32, Day 36, Day 39, Day 43, Day 46, Day50 and Day 53.  A window of +1 day is allowed.  Subject between the ages of 1-17 will have their A-101 study 
medication applied by a parent or 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. 
6 A-101 will only be dispensed to subjects who have not cleared all their warts, or who have developed new warts, and will be starting a new 8-week treatment 
cycle. 
 Table 3 Safety Observation Assessments for Subjects that are Clear at Visit 1 and Remain Clear 
Visit  
V1 
V2 
V3 
V4 
EOS 
Treatment Day 
Day 1 
Week 6 (Day 42) 
Week 12 (Day 84) 
Week 18 (Day 126) 
Week 26 (Day 182) 
Window 
 
+7 Days 
+ 7 Days 
+ 7 Days 
+ 2 Days 
In Office Visit 
▲1 
 
 
 
▲ 


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Protocol Number: A-101-WART-303  
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Visit  
V1 
V2 
V3 
V4 
EOS 
Phone Call 
 
▲2 
▲2 
▲2 
 
Informed Consent 
▲ 
 
 
 
 
Inclusion Criteria/Exclusion Criteria 
▲ 
 
 
 
 
Concomitant therapies 
 
▲ 
▲ 
▲ 
▲ 
Adverse Events 
▲ 
▲ 
▲ 
▲ 
▲ 
1Visit 1 of A-101-WART 303 may occur on the same day as Visit 13 of A-101-WART 301 or A-101-WART 302. 
2 Investigational site staff will contact via a documented phone call on Visit 2 Day 42, Visit 3 Day 84, Visit 4 Day 126 and Visit 5 Day 182. During the phone 
calls sites are to ask the subject if they have had any new warts develop or if a wart that was previously treated has recurred.  If a subject has had a new wart 
develop or a previously treated wart has recurred, then the subject is to be scheduled for an in -office visit to start an 8-week treatment course with A-101 study 
medication.  Subjects are to be instructed to contact the investigational site as soon as they think a new wart (or a recurrence) has developed.  The 8-week 
treatment period can start no later than Day 122.  Refer to Table 2 for the 8- week treatment schedule.   
 


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9. 
STUDY ASSESSMENTS 
9.1. 
Identification of Common Warts 
Subjects who have completed participation in the A-101-WART 301 or A-101-WART-302 study 
are eligible to enroll into the A-101-WART -303 study.  Subjects that were previously treated on 
the double- blind phase 3 study whose warts have recurred, were not treated or who develop new 
warts during the observation period of A-101-WART -303 are also eligible to receive treatment 
with A-101 Topical Solution 45% twice a week for 8 weeks.  An 8-week treatment period may 
begin anytime between Day 1 and Day 122.  
Warts that are identified by the treating investigator must meet the following criteria: 
• Subject may have 1 wart and up to 6 common warts treated during an 8-week treatment 
period 
• Identified warts must have a longest axis of ≤8 mm.    
• Be a discrete lesion, i.e. each wart meeting the entry criteria must be clearly 
separated from other warts  
• 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). 
Each identified wart will be identified on the body charts in the subject’s eCRF.   
9.2. 
Common Wart Dimensions and Physician’s Wart Assessment (PWA) 
Each identified wart that will be treated with A-101 study medication will be measured using the 
Aclaris supplied ruler.  The longest axis of each identified wart will be documented on the subject’s 
eCRF.   
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. 
During an 8-week treatment period, subjects will have their identified warts assessed using the 
PWA at the following time-points: Day 1, Day 29, Day 60 and Day 182. 
The Investigator will assess each identified common wart and report the one integer that best 
describes the common wart severity using the following scale.


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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. 
Common warts that are assessed by the investigator as having cleared (PWA =0) will be instructed 
not to continue to apply the A-101 study medication.   
Refer to Appendix 2 for the PWA Site Manual. 
9.3. 
Phone Call Visits 
Subjects that are enrolled to the study that do not have any identified warts to be treated will 
complete the Visit 1 (can be the same day as V13 of A-101-WART-301 or A-101-WART-302) 
assessment in the office and then will have telephone contact visits on Day 42, Day 84, and Day 
126.   During these calls site staff will ask the subject if they have any adverse events that they 
feel are related to their previous treatment with A-101 Topical Solution and if they have had a 
new wart develop or if they have had a recurrence of a wart that was previously treated on the A-
101-WART 301 or A-101-WART 302 study.  If a subject has a new wart or a recurrence they 
can be scheduled for an in-office visit and initiate treatment on another 8-week treatment period 
with A-101 study medication.  If an 8-week treatment period is started then all assessments 
outlined in Table 2 must be followed.  A subject cannot start an 8-week treatment period after 
study Day 122. 
 


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10. 
STUDY TREATMENT 
10.1. 
Investigational Study Medication 
The study medication for this study is open label A-101 45%.  All study medications are clear, 
colorless solutions which are indistinguishable in physical appearance. 
Table 4: 
Study Medication Information 
Study Medication 
Name 
A-101 45% 
Manufacturer 
James Alexander Corporation, Blairstown NJ 
A-101 concentration 
(%) 
45 
Pharmaceutical Form 
Solution 
Storage Conditions 
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* 
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) 
*Excursions from these temperature ranges must be reported to Aclaris. 
10.2. 
Subject Randomization 
This is an open label study.    
10.3. 
Study medication packaging, storage, and dispensing 
A-101 Topical Solution 45% 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. 


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Open label subject kits will contain 20 A-101 Topical Solution 45% applicators.  The subject kits 
will remain at the investigational site and the site staff will dispense study medication applicators 
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 A-101 study medication applicators that are 
to be used at home.  
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 destroyed after accountability has been completed. 
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. 
The investigational center staff member must comply with the study medication storage 
conditions outlined in Section 10.1.   
Subjects who have warts identified for treatment with A-101 Topical Solution, 45% will be 
instructed to treat each wart according to the technique outlined in Section 10.7.  Subjects that 
are 18 years of age and older will apply their own study medication and subjects age 1 to 17 will 
have their study medication applied by a parent or legal guardian.   
Identified warts are to be treated twice a week for up to 8 weeks (maximum 16 applications) or 
until the wart has cleared.  Subjects are to be instructed to apply the A-101 study medication on 
the following days:  Day 1, Day 4, Day 8, Day11, Day 15, Day 18, Day 22, Day 25, Day 29, Day 
32, Day 36, Day 39, Day 43, Day 46, Day 50 and Day 53.  A window of +1 day is allowed.  


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Protocol Number: A-101-WART-303 
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Subjects (or parents/legal guardians) are to apply the A-101 study medication in the office on the 
following days:  Day 1 and Day 29.      
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 instruct 
the subject/parent or guardian to:  
o Washing their hands prior to applying the study medication.   
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 2.  


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Protocol Number: A-101-WART-303 
Protocol Version 3:  14 February 2019 
 
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Figure 2: 
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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Protocol Number: A-101-WART-303 
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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.     
Subjects 18 years of age and older will apply their A-101 study medication to his/her identified 
common warts.  Study medication will be applied in the office on Day 1 and Day 29 prior to the 
PWA being performed. 
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 
• 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. 
10.8. 
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 and document all at home treatment applications on the subject 
diary. 
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) 
• 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. 
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. 
10.9. 
Other Study Supplies 
Aclaris Therapeutics, Inc. will provide: 
• An appropriate ruler, or other instrument, for measuring of all common wart dimensions;  
• Nitrile gloves 
• Zip top plastic bags 
• Supplies and instructions for collecting, labeling, shipping and result reporting for the 
clinical laboratory tests from ACM Laboratories; 


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10.10. 
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. 
10.11. 
Breaking the Blind 
Not applicable as this is an open label study. 


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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. 
For subjects starting an 8-week treatment schedule for an identified wart, topical products (e.g., 
moisturizers, sunscreens, etc.) must not be applied to any of their identified common warts 
within 12 hours prior to any treatment application (Note: routine cleansing products are 
allowed). 
 
After the completion of a treatment application, 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. 
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. 
12.1. 
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 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) 
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 
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: 
o Perform an LSR assessment. 
Subjects are to remain in the clinic for 20 minutes after the application of their study medication.   
Any local skin reactions or other adverse experiences that occur during this time period must be 


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documented as an adverse event.   
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 OR No signs or symptoms present. 
1 
Asymptomatic or mild symptoms OR clinical or diagnostic observations only OR 
intervention not indicated. 
2 
Moderate OR minimal, local or noninvasive intervention indicated. 
3 
Severe or medically significant but not immediately life threatening OR disabling OR 
limiting self-care of activities of daily living. 
. 
12.2. 
Clinical Laboratory Sampling 
Subjects that do not have their Visit 1 the same day as Visit 13 of either A-101-WART 301 or A-
101-WART 302 will have to have a clinical chemistry and CBC performed.  Non-fasting blood 
samples for clinical laboratory analysis will be collected by a qualified staff member on Day 182 
for all subjects.  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 
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 


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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 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. 
 


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13. 
ADVERSE EVENTS 
13.1. 
Definitions 
13.1.1. 
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. 
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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13.1.2. 
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. 
 
13.1.3. 
Adverse Event Reporting Period 
The investigator must start reporting non-serious AEs starting with the subject’s first study 
medication treatment continuing until the subject’s last study visit. 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 the 
subject’s last study visit (regardless of relationship to study medication).  If a subject experiences 
a SAE after the subject’s last study visit, 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. 
13.1.4. 
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. 


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Mild – Awareness of signs or symptom, but easily tolerated 
Moderate – Discomfort, enough to cause interference with usual activity 
Severe – Incapacitating with inability to perform usual activity. 
13.1.5. 
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. 
13.2. 
Reporting Procedures 
13.2.1. 
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. 


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13.2.2. 
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 
2. 
Immediately inform the Aclaris of the SAE by entering the event in to the Axiom database. If the 
Axiom database is unavailable, the site must fax a provided paper SAE form to Aclaris at the number 
below: 
 
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 entered in to the Axiom database. 
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 
entered in to the Axiom database. 
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). 
13.2.3. 
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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14. 
STATISTICAL CONSIDERATIONS 
Details of all statistical summaries and analyses will be provided in the study specific Statistical 
Analysis Plan (SAP). 
14.1. 
Sample Size and Power Considerations 
The sample size is based on an estimate of how many patients will be required to provide at least 
100 subjects requiring repeated treatment for a wart over the course of the study. 
• By recruiting 400 subjects, we estimate 200 subjects will have received active treatment 
in the A101-WART 301/302 studies. 
• We expected approximately 26% of warts treated in A-101-WART-301/302 studies to be 
clear at the end of the A101-WART 301/302 studies. 
• Based on the assumption that 26% of warts will be clear, at least 148 subjects will require 
exposure to active treatment. 
• We anticipate that some subjects originally randomized to vehicle will be exposed to 
active treatment. 
As a result, the study should exceed the target of exposing more than 100 subjects to repeated 
treatments over the course of the study.  
14.2. 
Analysis Populations 
The Intent-to-Treat (ITT) population will consist of all subjects consented in the study. 
14.3. 
Statistical Analysis of Efficacy 
Unless otherwise stated, all efficacy summaries and analyses will be conducted using the ITT 
population.  All efficacy summaries and analyses will be produced for the following groups: 
• Subjects treated in the study that were randomized to active treatment during the previous 
A101-WART 301/302 study. 
• Subjects treated in the study that were randomized to vehicle during the previous A101-
WART 301/302 study. 
• Subjects treated in the study overall. 
• Subjects not requiring treatment during the study that were randomized to active 
treatment during the previous A101-WART 301/302 study. 
• Subjects not requiring treatment during the study that were randomized to vehicle during 
the previous A101-WART 301/302 study. 
• Subjects not requiring treatment in the study overall. 
• All subjects combined 
 


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The primary efficacy analysis will be the effectiveness of A-101 45% based on the proportion of 
subjects who achieve complete clearance (PWA=0) of all identified common warts at any 
scheduled visit.  Any identified common wart for a subject that has missing PWA data will be 
treated as not clear for the purpose of the primary efficacy analysis. 
 
Four secondary efficacy analyses will be performed:  
• Durability of response:  for warts achieving a status of Clear (PWA=0), the number of 
weeks the wart remains clear will be tabulated and these results will be summarized using 
descriptive statistics.  The proportion of these warts that remain clear at the end of the 
study will also be presented.   
• Mean per-subject percent of treated warts that are Clear (PWA=0) at each visit will be 
summarized using descriptive statistics.    
• Proportion of subjects with a single wart at baseline whose wart is Clear (PWA=0) will 
be summarized using descriptive statistics by visit. 
• Median time to achieve onset of Clearance (PWA=0) for all treated warts.  
Efficacy summaries will be supported by listings of PWA data. 
14.4. 
Statistical Analysis of Safety Data 
Unless otherwise stated, all safety summaries will be conducted using the ITT population.  All 
safety summaries will be produced for the following groups: 
• Subjects treated in the study that were randomized to active treatment during the previous 
A101-WART 301/302 study. 
• Subjects treated in the study that were randomized to vehicle during the previous A101-
WART 301/302 study. 
• Subjects treated in the study overall. 
• Subjects not requiring treatment during the study that were randomized to active 
treatment during the previous A101-WART 301/302 study. 
• Subjects not requiring treatment during the study that were randomized to vehicle during 
the previous A101-WART 301/302 study. 
• Subjects receiving active treatment during the study or the previous A101-WART 
301/302 study.  
The proportion of subjects with treatment emergent adverse events will be tabulated and 
presented by System Organ Class and Preferred Term from the Medical Dictionary for 
Regulatory Activities (MedDRA).  Likewise, the proportion of subjects with serious AEs will be 
summarized.  Adverse event summaries will be presented 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 SAP. 
 


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Local skin reaction (LSR) scores and clinically relevant abnormal laboratory results will be 
tabulated and presented at the subject level.  For each LSR sign and at each in-house visit, the 
proportion of subjects who had at least one treated wart with LSR severity >= 1 will be 
summarized. 
Safety summaries will be supported by listings of all adverse events, laboratory results, and LSR 
data. 
14.5. 
Interim Analysis 
No formal interim analysis will be conducted for this study.  


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15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
15.1. 
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. 
15.2. 
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. 
15.3. 
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. 
15.4. 
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. 
15.5. 
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. 
15.6. 
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. 
15.7. 
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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16. 
ETHICS AND GENERAL STUDY CONDUCT 
CONSIDERATIONS 
16.1. 
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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16.2. 
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. 
16.3. 
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. 
16.4. 
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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17. 
REFERENCES 
1. Chan HP, Maibach HI, 2008.  "Hydrogen Peroxide, Blanching, and Skin: an Overview". 
Cutaneous and Ocular Toxicology, 307-309. 
2. Richardson. 1866. "On the Introduction of Peroxide of Hydrogen as a Medicine." The 
Lancet 87 (2220):300. 
3. 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. 
4. 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 
5. Schumb WC, Satterfield CN, and Wentworth RL. 1955. Hydrogen Peroxide. New York: 
Reinhold Publishing Comp. 
6. Watt BE, Proudfoot AT, Vale JA. 2004 . "Hydrogen Peroxide Poisoning (Review)." 
Toxicological Reviews 51-57. 
7. 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-303 SUBJECT INSTRUCTION SHEET FOR 
IDENTIFIED WARTS TO BE TREATED 
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 1: 
• 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 application of A-101 
study medication. 
• Do not wash/submerge the treated common warts for at least 6 hours after the application of A-
101study medication.   
• Do not apply any topical products to the treated common warts for at least 6 hours after the 
application of A-101 study medication. 
• Do not occlude, bandage or otherwise cover the common wart treatment area (loose-fitting 
clothing is permissible) for at least 6 hours after the application of A-101 study medication. 
• 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. 
 


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STUDY VISIT SCHEDULE: 
VISIT 2: Day 15 (Phone Call Visit) 
Date:                            Time: 
VISIT 3: Day 29 (In Office Visit) 
Date:                            Time: 
VISIT 4 Day 43 (Phone Call visit) 
Date:                            Time: 
VISIT 5 Day 60 (In Office Visit): 
Date:                            Time: 
VISIT 6 Day 102 (Phone Call Visit) 
Date:                            Time: 
VISIT 7 Day 144 (Phone Call Visit): 
Date:                            Time: 
VISIT 8: Day 182 (In Office Visit) 
Date:                            Time: 
 
 
 
 
 
Study Medication Application: 
 
• 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. 
• Wear nitrile examination gloves during the treatment that were provided to you by your 
doctor.  Latex gloves are prohibited 
• Do not apply the study medications to eyes, nose, mouth, mucous membranes, or open 
wounds. 
• 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. 


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• 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 the provided plastic bag and placed in your trash can.   


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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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