Clinical trial NCT03148691
Conditions: Seborrheic Keratosis
Sponsor: Aclaris Therapeutics, Inc.
Start date: 2017-05-17; Completion date: 2018-04-03
Enrollment: 253 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the safety and effectiveness of 2 concentrations of A-101 compared to Vehicle for the treatment of 4 seborrheic keratosis (SK) Target Lesions on the trunk, extremities and face.

Detailed description:
The primary objective of this study is to evaluate the safety and effectiveness of 2 concentrations of A-101 compared to Vehicle for the treatment of 4 seborrheic keratosis (SK) Target Lesions on the trunk, extremities and face.

The secondary objectives of this study include duration of response of A-101. During the study, the investigator will identify 4 eligible SK Target Lesions on each subject on the trunk, extremities and face. For each subject, at least 1 SK Target Lesion must be on the face and at least 1 Target Lesion must be on the trunk or extremities. The Target Lesions will be treated at a maximum of two treatment visits.

Arms: arm 1: Vehicle Topical Solution arm 2: A-101 Low Dose Topical Solution arm 3: A-101 High DoseTopical Solution
Interventions: intervention 1: A-101
Intervention descriptions: intervention 1: Topical Solution

Protocol documents:
Prot_SAP_000.pdf: 
Aclaris Therapeutics, Inc.  
 
Protocol Number: A-101-SEBK-204 
Amendment 2:  03 MAY 2017 
Page 1 of 67 
 
 
 
Date:    04 MAY 2017                                                                                                
CLINICAL STUDY PROTOCOL 
 
Protocol Number: A-101-SEBK-204 
Amendment 2 
Version 3.0 
04 May 2017 
 
A Phase 2 Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Study of the 
Safety and Effectiveness of A-101 (hydrogen peroxide)  Topical Solution in Subjects with 
Seborrheic Keratosis Lesions on the Trunk, Extremities and Face 
 
 
Sponsor 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Telephone: (484) 324-7933 
Facsimile: (484) 320-2344 
 
Study Contact 
Judy Schnyder 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive  
Suite 400  
Malvern, PA 19355 
Telephone:  484-329-2144 
Email:  jschnyder@aclaristx.com 
 
Medical Monitor 
Stuart D. Shanler, MD 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive  
Suite 400  
Malvern, PA 19355 
Telephone:  484-321-5555 
Serious Adverse Event Facsimile:  484-324-2359 
Email:  sshanler@aclaristx.com 
 
 
 
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. 




Protocol: A-101-SEBK-204 
Aclaris Therapeutics, Inc. 
 
 
Page 3 of 67 
 
 
 
Date:  04 MAY 2017                                                                                                   
 
INVESTIGATOR SIGNATURE PAGE 
Protocol Number:  A-101-SEBK-204 
 
Protocol Title:  A Phase 2 Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Study of the 
Safety and Effectiveness of A-101 (hydrogen peroxide)  Topical Solution in Subjects with Seborrheic 
Keratosis Lesions on the  Trunk,  Extremities, and Face  
Protocol Version  
Version 3.0: 04 MAY 2017 
 
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 from each prospective trial subject or each prospective trial 
subject’s legal representative prior to conducting any protocol-specified procedures.  The Informed 
Consent 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 within 24 hours 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 


Protocol: A-101-SEBK-204 
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Date:  04 MAY 2017                                                                                                   
 
 
 
 
 
 
Table of Contents 
1. 
SYNOPSIS .................................................................................................................................................... 7 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................................................. 11 
2. 
INTRODUCTION ...................................................................................................................................... 13 
2.1. 
Summary ................................................................................................................................................... 13 
2.2. 
Summary of Previous Clinical Trials with A-101 Solution in Seborrheic Keratosis .............. 14 
2.2.1. 
A-101-SEBK-301 ................................................................................................................................... 14 
2.2.2. 
A-101-SEBK-302 ................................................................................................................................... 15 
2.2.3. 
A-101-SEBK-303 ................................................................................................................................... 16 
3. 
STUDY RATIONALE AND OBJECTIVES ....................................................................................... 17 
3.1. 
Rationale .................................................................................................................................................... 17 
3.2. 
Study Objectives ...................................................................................................................................... 17 
3.2.1. 
Primary Objective ................................................................................................................................ 17 
3.2.2. 
Secondary Objective ............................................................................................................................ 17 
4. 
STUDY DESIGN ........................................................................................................................................ 17 
4.1. 
Number of Subjects and Study Centers ............................................................................................. 18 
4.2. 
Duration of Study .................................................................................................................................... 18 
5. 
STUDY ENTRY CRITERIA .................................................................................................................. 18 
5.1. 
Inclusion Criteria .................................................................................................................................... 18 
5.2. 
Exclusion Criteria ................................................................................................................................... 19 
5.3. 
Removal of Patients from Study Therapy ......................................................................................... 20 
5.4. 
Withdrawal Procedures ......................................................................................................................... 21 
5.5. 
Subject Replacement .............................................................................................................................. 21 
5.6. 
Subject Identifier (SI) ............................................................................................................................. 21 
6. 
STUDY PROCEDURES ........................................................................................................................... 21 
7. 
STUDY TREATMENT............................................................................................................................. 24 
7.1. 
Investigational Study Medication ........................................................................................................ 24 
7.2. 
Subject randomization ........................................................................................................................... 24 
7.3. 
Study medication packaging, storage and dispensing .................................................................... 25 
7.4. 
Drug Accountability ................................................................................................................................ 25 
7.5. 
Study Medication Treatment ................................................................................................................ 25 
7.5.1. 
Preparing the Study Medication for Application ......................................................................... 26 
7.5.2. 
Applying Study Medication to Trunk/Extremities ....................................................................... 28 
7.5.3. 
Applying Study Medication to the Face .......................................................................................... 29 


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Date:  04 MAY 2017                                                                                                   
7.6. 
Video Recording of Study Medication Application......................................................................... 30 
7.7. 
Dose modification .................................................................................................................................... 30 
7.8. 
Previous and Concomitant Therapies ................................................................................................ 31 
7.8.1. 
Previous therapies ................................................................................................................................ 31 
7.8.2. 
Concomitant therapies ........................................................................................................................ 31 
7.8.3. 
Prohibited therapies ............................................................................................................................. 31 
7.9. 
Breaking the Blind .................................................................................................................................. 32 
8. 
ASSESSMENTS OF CLINICAL EFFICACY .................................................................................... 32 
8.1. 
Target Lesion Identification ................................................................................................................. 32 
8.1.1. 
Standardized photography ................................................................................................................. 34 
8.1.2. 
Physician’s Lesion Assessment (PLA) ............................................................................................. 35 
8.1.3. 
Lesion Dimensions ................................................................................................................................ 35 
8.2. 
Subject Instructions ................................................................................................................................ 36 
8.3. 
Subject Satisfaction Survey ................................................................................................................... 36 
8.4. 
Other Study Supplies .............................................................................................................................. 37 
9. 
ASSESSMENT OF SAFETY .................................................................................................................. 37 
9.1. 
Local Skin Reactions (LSR) .................................................................................................................. 37 
9.2. 
Vital signs .................................................................................................................................................. 39 
9.3. 
Clinical laboratory sampling ................................................................................................................ 39 
9.4. 
Urine pregnancy tests ............................................................................................................................. 40 
9.5. 
Other Evaluations ................................................................................................................................... 40 
9.5.1. 
Demographics and medical history .................................................................................................. 40 
9.5.2. 
Standardized photography ................................................................................................................. 41 
10. 
ADVERSE EVENTS ................................................................................................................................ 42 
10.1. 
Definitions ................................................................................................................................................. 42 
10.1.1. 
Adverse events (AE) ............................................................................................................................. 42 
10.1.2. 
Serious adverse event (SAE) .............................................................................................................. 43 
10.1.3. 
Adverse event reporting period ......................................................................................................... 43 
10.1.4. 
Severity .................................................................................................................................................... 44 
10.1.5. 
Relationship to study medication ...................................................................................................... 44 
10.2. 
Reporting Procedures ............................................................................................................................. 44 
10.2.1. 
Procedures for reporting adverse events ........................................................................................ 44 
10.2.2. 
Procedure for reporting a serious adverse event .......................................................................... 45 
10.2.3. 
Withdrawal Due to an Adverse Event ............................................................................................. 45 


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Date:  04 MAY 2017                                                                                                   
11. 
PREGNANCY ............................................................................................................................................. 46 
12. 
STATISTICAL CONSIDERATIONS .................................................................................................. 47 
12.1. 
Sample Size and Power Consideration ............................................................................................... 47 
12.2. 
Statistical Analysis of Efficacy ............................................................................................................. 47 
12.3. 
Statistical Analysis of Safety Data ....................................................................................................... 48 
12.4. 
Interim Analysis ....................................................................................................................................... 48 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE ................................................................. 48 
13.1. 
Protocol Amendments ............................................................................................................................ 48 
13.2. 
Protocol Deviations, Violations and Exceptions ............................................................................... 48 
13.3. 
Training ..................................................................................................................................................... 49 
13.4. 
Monitoring ................................................................................................................................................ 49 
13.5. 
Data Management ................................................................................................................................... 50 
13.6. 
Quality Assurance ................................................................................................................................... 50 
13.7. 
Record Retention ..................................................................................................................................... 50 
14. 
ETHICS AND GENERAL STUDY CONDUCT CONSIDERATIONS ....................................... 51 
14.1. 
Institutional Review Board (IRB)/Ethics Committee (EC)...................................................... 51 
14.2. 
Ethical Conduct of the Study ............................................................................................................ 52 
14.3. 
Regulatory Documents ........................................................................................................................... 52 
14.4. 
Contractual Requirements .................................................................................................................... 52 
15. 
APPENDICES ............................................................................................................................................. 53 
15.1. 
Subject Instruction Sheet ...................................................................................................................... 53 
15.2. 
Physician Lesion Assessment Scale-Training Manual (12JAN2016) .................................. 55 
16. 
References .................................................................................................................................................... 67 
 


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Date:  04 MAY 2017                                                                                                   
 
1. 
SYNOPSIS 
Protocol Number A-101-SEBK-204 Synopsis 
Protocol Number: 
 
 
Protocol Title:   
A Phase 2 Randomized, Double-Blind, Vehicle-Controlled, Parallel Group 
Study of the Safety and Effectiveness of A-101 (hydrogen peroxide)  
Topical Solution in Subjects with Seborrheic Keratosis Lesions on the 
Trunk, Extremities and Face  
Sponsor: 
 
Aclaris 
 
Phase of Development: 
 
Phase 2 
Study Drug Description: 
 
A-101 Solution (40% and 45%) is a hydrogen peroxide solution that will be supplied in a glass ampule 
with an applicator to be applied to seborrheic keratosis lesions of the trunk, extremities and face..     
 
The study drug, A-101 (hydrogen peroxide) 40% and 45% Topical Solution (hereafter referred to as A-
101) is a colorless solution that must be stored at room temperature (20-25º C or 68 -77 º F), protected 
from light. 
 
Study Objectives: 
 
Primary: 
 
The main objective of this study is to evaluate the effectiveness of A-101 40% and A-101 45% versus 
vehicle for the treatment of 4 seborrheic keratosis (SK) Target Lesions on the trunk, extremities and face.  
 
Secondary: 
 
The secondary objectives of this study include: 
• 
Duration of response 
• 
Safety  
Study Design:   
This is a phase 2, multicenter, randomized study to evaluate the safety and efficacy of A101 40% and 
A101 45% versus vehicle.  Subjects will be required to have a total of 4 target seborrheic keratosis (SK) 
lesions located on their trunk, extremities and face.  At least one of the 4 target lesions must be on the 
face and at least one of the target lesions must be on the trunk or extremities.   
 
Subjects will be randomized to one of 3 treatment arms in a 1:2:2 ratio.  Fifty subjects will be randomized 
to the Vehicle treatment arm and 100 subjects will be randomized to each A-101 active treatment arm.  
Subjects will receive a maximum of 2 treatments [Day 1 (Visit 2) and re-treatment on Day 22 (Visit 4) if 
a target lesion meets the criteria for re-treatment].   The duration of study participation is anticipated to be 
up to a maximum of 124 days per subject.   
 
Safety will be evaluated based on clinical laboratory studies (hematology and clinical chemistry), vital 
signs, assessment of local skin reactions (LSRs), assessment of adverse events (AEs), and concomitant 
medication review.   
 


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Date:  04 MAY 2017                                                                                                   
Efficacy will be evaluated based on assessment of each Target Lesion according to the Physician’s Lesion 
Assessment (PLA).  Sites will be required to take standardized color photographs of each of the Target 
Lesions to assist with the documentation of the location of each of the Target Lesions throughout the 
study.   
 
Number of Patients to be Enrolled: 
 
A total of 250 evaluable subjects will be randomized to the study.   
Number of Study Sites: 
 
This study will be conducted in the US only at approximately 9 treatment centers.   
Inclusion Criteria: 
Subjects must meet all of the following criteria to be considered for participation in this study.   
1. Subject is able to comprehend and is willing to sign an informed consent for participation in this 
study. 
2. Male or female ≥ 18 years old. 
3. Subject has a clinical diagnosis of stable clinically typical seborrheic keratosis. 
4. Subject has 4 appropriate seborrheic keratosis Target Lesions on the trunk, extremities and face, 
with at least 1 Target lesion on the face and at least 1 Target Lesion on the trunk or extremities.  
The 4 identified Target Lesions must meet the requirements as defined below: 
a. Have a clinically typical appearance 
b. Have a Physician's Lesion Assessment of ≥ 2 
c. Length that is ≥ 5mm and ≤15 mm 
d. Width that is ≥ 5mm and ≤15 mm 
e. Thickness that is ≤ 2mm 
f. Be a discrete lesion 
g. Be the only SK lesion present when centered in the area outlined by the provided circular 
template 
h. Not be covered with hair which, in the investigator’s opinion, would interfere with the 
study medication treatment or the study evaluations 
i. 
Not be in an intertriginous fold 
j. 
Not be on the eyelids 
k. Not be within 5mm of the orbital rim 
l. 
Not be pedunculated   
5. Subject chemistry and complete blood count results are within normal limits. If any of the 
laboratory values are outside normal range, the treating investigator must assess the 
value/s as NOT clinically significant and document this in the subject’s medical chart in 
order for the subject to be eligible for randomization.   
6. Woman of childbearing potential must have a negative urine pregnancy test within 14 days of the 
first application of study drug and agree to use an active method of birth control for the duration 
of the study.  
7. Subject is non-pregnant and non-lactating. 
8. 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 any Target Lesion or which exposes 
the subject to an unacceptable risk by study participation.   
9. Subject is willing and able to follow all study instructions and to attend all study visits.  
 
Exclusion Criteria: 
Subjects are excluded from this study if any 1 or more of the following criteria is met: 
1. Subject has clinically atypical and /or rapidly growing seborrheic keratosis lesions. 


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Date:  04 MAY 2017                                                                                                   
2. Subject has presence of multiple eruptive seborrheic keratosis lesions (Sign of Lesser -Trelat). 
3. Subject has current systemic malignancy. 
4. Subject has used any of the following systemic therapies within the specified period prior to Visit 
1: 
• 
Retinoids; 180 days 
• 
Corticosteriods; 28 days 
• 
Antimetabolites (e.g., methotrexate); 28 days 
5. Subject has used any of the following topical therapies within the specified period prior to Visit 1 
on, or in a proximity to any Target Lesion, 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], photo-
dynamic therapy [PDT]; 180 days 
• 
Liquid nitrogen, electrodesiccation, curettage, imiquimod, 5-flurouracil (5FU), or ingenol 
mebutate; 60 days 
• 
Hydrogen peroxide; 90 days 
• 
Retinoids; 28 days 
• 
Microdermabrasion or superficial chemical peels; 14 days 
• 
Corticosteriods or antibiotics; 14 days. 
6. 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 Target Lesion 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 
• 
Body art (e.g. tattoos, piercing, etc.); currently 
• 
Excessive tan; currently.  The use of self-tanning lotions/sprays are prohibited. 
7. Subject has a history of sensitivity to any of the ingredients in the study medications. 
8. Subject has any current skin 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.  
9. Participation in another therapeutic investigational drug trial in which administration of an 
investigational study medication occurred within 30 days prior to Visit 1.  
Duration of Treatment 
The duration of the study participation is anticipated to be a maximum of 124 days per subject.  The final 
visit (Visit 8) has a maximum allowable visit window of 14 days:  Study visits are: 
• 
Visit 1 (Day -13 to 0) screening 
• 
Visit 2 (Day 1) randomization; study medication treatment 
• 
Visit 3 (Day 8) follow up visit  
• 
Visit 4 (Day 22) follow up visit; Target Lesions that meet the retreatment criteria will receive a 
second study medication treatment 
• 
Visit 5 (Day 29) follow up visit 
• 
Visit 6 (Day 50) follow up visit 
• 
Visit 7 (Day 78) follow up visit 
• 
Visit 8 (Day 106) follow up visit; end of study 
Criteria for Evaluation 
Efficacy: 
The investigator will evaluate the severity of each SK Target lesion using the Physician’s Lesion 
Assessment (PLA) 


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Date:  04 MAY 2017                                                                                                   
 
Safety: 
Safety will be evaluated by following adverse events, clinical laboratory exams, vital signs, concomitant 
medications, as well as through skin examinations and general physical exams.   
 
 
Study Drug Administration 
 
Study drug medication will be applied to each of the four Target Lesions during Visit 2 by the treating 
physician or a member of the investigational site staff who is a trained healthcare professional.     
 
Study medication must be applied to each of the Target Lesions for approximately 20 seconds.  Each 
Target Lesion will be treated up to 4 times while waiting approximately 60 seconds between each 
application.   
 
Study medication must be applied to a total of 4 SK Target Lesions.  At least one of the SK Target 
Lesions must be on the face and at least one must be on the trunk or extremities. 
 
Statistical Methods 
 
Efficacy Analysis 
The primary effectiveness analysis will consist of pair-wise comparison between each active treatment 
group and the vehicle treatment group, and between the two active treatment groups, based on the mean 
of per-subject percentages of target lesions judged to be clear on the PLA (PLA = 0) at Visit 8.  To 
conduct this analysis, the percentage of each subject’s target lesions judged to be clear on the PLA at 
Visit 8 will first be calculated for each subject.  Then the analysis will calculate the mean of this 
parameter for each treatment group (yielding an estimate of the mean percentage of clear lesions across 
subjects), and an analysis of variance (ANOVA) model will be used to perform all pair-wise comparisons 
among the treatment groups.  Pair-wise comparisons will be conducted on the least-squares means using 
the overall pooled error term of the model.  All efficacy analyses will be based on the per protocol (PP) 
population, defined as all randomized subjects who completed the study with no major protocol violation.  
 
A secondary effectiveness analysis will be conducted using the same methodology as the primary efficacy 
analysis based on the mean of per-subject percentages of target lesions judged to be clear or near-clear on 
the PLA (PLA ≤1) at Visit 8. 
 
Safety Analysis 
Safety endpoints for adverse events (AEs) include the following:  incidences of all treatment-emergent 
AEs (TEAEs) and all serious AEs (SAEs); by severity, by relationship to study drug and discontinuation 
of patients from study due to AEs.  Safety endpoints for AEs, clinical laboratory tests, vital signs, and 
physical examinations and local skin reactions will be specified in the statistical analysis plan (SAP).  All 
safety endpoints will be summarized using descriptive statistics.   
 


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Date:  04 MAY 2017                                                                                                   
 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Term 
AE  
Adverse Event 
ANCOVA 
Analysis of Covariance 
°C 
Degrees Centigrade 
CMH 
Cochran-Mantel-Haenszel 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CS 
Clinically Signficant 
e.g.  
for example, (Latin; exempla gratia) 
EC 
Ethics Committee 
°F 
Degrees Fahrenheit 
FDA 
Food and Drug Administration 
5FU 
5 Fluorouracil 
G 
Gram 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
H2O2 
Hydrogen Peroxide 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization  
i.e.  
that is (Latin; id est) 
IPL 
Intense Pulsed Laser 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
LOCF 
Last Observation Carried Forward 
LSR 
Local Skin Reactions 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
Milliliter 
Mm 
Millimeter 


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Date:  04 MAY 2017                                                                                                   
Abbreviation 
Term 
NCS 
Not Clinically Significant 
OTC 
Over-The-Counter 
PDT 
Photodynamic Therapy 
PLA 
Physician’s Lesion Assessment 
PP 
Per Protocol 
SAE 
Serious Adverse Event 
SI 
Subject Identifier 
SK 
Seborrheic Keratosis 
SOP 
Standard Operating Procedure 
US 
United States 
WOCBP 
Women of childbearing potential 


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Date:  04 MAY 2017                                                                                                   
2. 
INTRODUCTION 
2.1. 
Summary 
Seborrheic keratosis (SK) is one of the most common skin tumors in man. These benign 
epithelial skin tumors are most commonly seen in older individuals, increasing in prevalence 
with increasing age, and affect men and women roughly equally. While the growths may be 
solitary, they often occur in large numbers and typically present as well demarcated, elevated or 
“stuck-on” appearing papules or plaques that may vary from flesh-colored, to shades of yellow, 
gray, brown, or black (Haffner C 2008). 
 
Though benign, SK lesions are often cosmetically worrisome to patients, must sometimes be 
distinguished from other benign or malignant skin tumors and may become pruritic, irritated, 
bleed, and may be painful when traumatized particularly when located in areas prone to friction 
and trauma, such as belt-lines and brassiere-strap lines.  
 
Patients may seek treatment of SK for cosmetic reasons, especially if they are large, pigmented, 
and/or if multiple lesions are present, or simply because the lesions are commonly associated 
with “old age”. Removal may be medically indicated, however, for lesions that become irritated, 
pruritic, inflamed, or painful, or for lesions that the clinician feels require histologic confirmation 
of the diagnosis. 
  
Numerous treatment options exist, and include a plethora of destructive/ablative modalities such 
as liquid nitrogen cryotherapy, electrodesiccation, lasers of various wavelengths (ablative and 
non-ablative), radio-frequency ablation, and surgical removal by curettage or surgical excision. 
There is, however, a notable lack of well-controlled clinical trials comparing the efficacy, 
complications, and complication rates of these treatments. There is great variability among 
practitioners in the methods employed using each of these techniques (e.g., variability in contact 
time and method of freezing the lesions with liquid nitrogen) with great variability of the results. 
None of these treatments is, in fact, approved by the Food and Drug Administration (FDA) for 
the treatment of seborrheic keratosis. While these methods can be effective, many require 
specialized training and/or the use of expensive equipment, they are painful and may require 
anesthesia and/or analgesia, and they are often complicated by significant adverse outcomes. 
Both hypopigmentation and hyperpigmentation, which may be transient, but are often 
permanent, are common, as is scarring at the treatment site, and the typical post-surgical risks of 
bleeding and infection increase the risk that the result of the treatment of these lesions may be 
worse than the disease itself (Pierson DBC 2003)  (Motley 2002) (McKee PH 2005). 
 


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Date:  04 MAY 2017                                                                                                   
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 
WC 1955) (Chan HP 2008) (Richardson, On Peroxide of Hydrogen, or Ozone, or Water as a 
Remedy: Continued from a Research Commenced in the Year 1858 1891) (Richardson, On 
Peroxide of Hydrogen, or Ozone, or Water, as a Remedy: Continued from Research Commenced 
in the Year 1858 1891) (Richardson, On the Introduction of Peroxide of Hydrogen as a Medicine 
1866) (Watt BE 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. 
 
Data from a proof of concept study (A-101-SEBK-201) demonstrated that topical treatment of 
SK lesions with A-101 Solution 40% and 32.5% has the potential to safely and effectively 
resolve SK lesions without the need for analgesia and/or anesthesia, and with a minimal risk of 
hypopigmentation, hyperpigmentation, or scarring. 
 
Further, data from two dose-ranging studies (A-101-SEBK-202 evaluating SK lesions on the 
trunk and extremities; A-101-SEBK-203 evaluating SK lesions on the face) demonstrated that 
topical treatment with A-101 Solution 40% is superior to both A-101 Solution Vehicle and A-
101 Solution 32.5% for safely and effectively treating seborrheic keratosis lesions in adult 
subjects and has an acceptable safety profile. 
 
2.2. 
Summary of Previous Clinical Trials with A-101 Solution in Seborrheic 
Keratosis 
2.2.1. 
A-101-SEBK-301 
A-101-SEBK-301 was a randomized, double-blind, vehicle-controlled, parallel-group study of 
A-101 and vehicle to investigate the effectiveness, safety, and tolerability in subjects with SK 
target lesions on the trunk, extremities, and face.  Subjects randomized to the study were able to 
receive up to 2 applications of A-101 40% or matching vehicle.   


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Date:  04 MAY 2017                                                                                                   
A total of 450 subjects were randomized and 435 (96.7%) completed the study. Among the 
15 subjects who discontinued, the reasons were similar between the treatment groups with the 
most frequent being a protocol violation (2.6% vehicle, 2.2% A-101). Two subjects (0.4% 
vehicle, 0.4% A-101) discontinued due to an AE or SAE. The mean age was 68.7 years (range 
42 to 90, 42.0% were at least 71 years old), 41.3% of subjects were male and 58.7% were 
female, and 97.8% were Caucasian. The most common Fitzpatrick skin types were 2 (46.9%) 
and 3 (27.3%). 
Treatment with A-101 40% showed statistically significant efficacy compared to treatment with 
vehicle based on the primary analysis.  
For the primary endpoint, the proportion of ITT subjects who achieved clearance (PLA = 0) of 
all 4 target lesions at Visit 8 (Day 106) was 4.0% with A-101 compared to 0.0% with vehicle 
(p = 0.0019).  For the secondary endpoint, the proportion of ITT subjects who achieved clearance 
of at least 3 of the 4 target lesions at Visit 8 was 13.45% with A-101 compared to 0.0% with 
vehicle (p < 0.0001). 
Treatment Emergent Adverse Events (TEAEs) were reported for 45 (19.8%) subjects in the 
vehicle group and 54 (24.2%) subjects in the A-101 group.  The most frequently reported TEAEs 
were nasopharyngitis (3.1% vehicle, 1.3% A-101), bronchitis (0.4% vehicle, 1.3% A-101), and 
upper respiratory tract infection (1.3% vehicle, 0.4% A-101).  Six (2.6%) subjects in the vehicle 
group had 8 SAEs and 4 (1.8%) subjects in the A-101 group had 4 SAEs.  The SAEs were all 
considered not related to study medication.  Two subjects, 1 in each treatment group, 
discontinued the study due to an SAE.  
LSRs were few and predominantly mild.  The LSRs of pruritus and stinging reported by subjects 
and crusting, edema, erythema, hyperpigmentation, scaling, and vesicles reported by the 
investigator following treatment and retreatment had generally resolved by Visit 8 (Day 106).  
There were no clinically significant changes during the study in laboratory evaluations or vital 
signs. 
2.2.2. 
A-101-SEBK-302 
A-101-SEBK-302 was a randomized, double-blind, vehicle-controlled, parallel-group study of 
A-101 and vehicle to investigate the effectiveness, safety, and tolerability in subjects with SK 
target lesions on the trunk, extremities, and face.  Subjects randomized to the study were able to 
receive up to 2 applications of A-101 40% Solution or matching vehicle.   
 
A total of 487 subjects were randomized and 461 (94.7%) completed the study. Among the 
26 subjects who discontinued, the reasons were similar between the treatment groups with the 
most frequent being a protocol violation (2.9% vehicle, 4.5% A-101). No subject discontinued 
due to an AE or SAE. The mean age was 68.7 years (range 45 to 91, 41.5% were at least 
71 years old), 41.7% of subjects were male and 58.3% were female, and 97.9% were Caucasian. 
The most common Fitzpatrick skin types were 2 (46.6%) and 3 (33.1%). 
 
Treatment with A-101 showed statistically significant efficacy compared to treatment with 
vehicle based on the primary analysis.  


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Date:  04 MAY 2017                                                                                                   
For the primary endpoint, the proportion of ITT subjects who achieved clearance (PLA = 0) of 
all 4 target lesions at Visit 8 (Day 106) was 7.8% with A-101 compared to 0.0% with vehicle 
(p < 0.0001).  For the secondary endpoint, the proportion of ITT subjects who achieved clearance 
of at least 3 of the 4 target lesions at Visit 8 was 23.0% with A-101 compared to 0.0% with 
vehicle (p < 0.0001). 
TEAEs were reported for 43 (17.7%) subjects in the vehicle group and 46 (18.9%) subjects in the 
A-101 group.  The most frequently reported TEAEs were sinusitis (1.6% vehicle, 1.6% A-101), 
nasopharyngitis (1.2% vehicle, 0.4% A-101), and herpes zoster (0.0% vehicle, 1.2% A-101).  
Four (1.6%) subjects in the vehicle group had 4 SAEs and 6 (2.5%) subjects in the A-101 group 
had 10 SAEs.  The SAEs were all considered not related to study medication.  No subject 
discontinued the study due to a TEAE or SAE. 
LSRs were predominantly mild.  The LSRs of pruritus and stinging reported by subjects and 
edema, erythema, and scaling reported by the investigator following treatment and retreatment 
had generally resolved by Visit 8 (Day 106).  
There were no clinically significant changes during the study in laboratory evaluations or vital 
signs. 
2.2.3. 
A-101-SEBK-303 
A-101-SEBK-303 was an open label safety study in which subjects received up to 4 applications 
of A-101 40% Solution to SK lesions on their face, trunk or extremities.   
 
A total of 147 subjects were enrolled and treated and 139 subjects (94.6%) completed the study.  
Five subjects withdrew consent and 3 subjects were lost to follow-up.  The mean age was 
68.4 years (range 35 to 94, 40.1% were at least 71 years old), 32.0% of subjects were male and 
68.0% were female, and 93.9% of subjects were Caucasian.  The most common Fitzpatrick skin 
types were 2 (48.3%) and 3 (32.0%). 
 
At Visit 12 (Day 148) in the ITT population, 10.9% of subjects had all 4 target lesions judged to 
be clear on the PLA (PLA = 0), 18.4% had at least 3 of 4 target lesions judged to be clear, and 
27.9% had all 4 target lesions judged to be clear or near clear (PLA ≤ 1).  In the PP population, 
the PLA average per-subject percent of target lesions judged to be clear at Visit 12 was 28.2%. 
 
TEAEs were reported for 25 (17.0%) subjects.  The most frequently reported TEAEs were 
cough, seasonal allergy, and sinusitis (2.0% each).  No TEAEs were reported as severe, no SAEs 
were reported, and no subject discontinued the study due to an AE or SAE. 
LSRs reported were predominantly mild and most commonly included transient pruritus, 
stinging, crusting, edema, erythema, and scaling post-treatment that usually resolved by the next 
visit.  Few lesions had LSRs at Visit 12. 
There were no clinically significant changes during the study in laboratory evaluations or vital 
signs. 
 


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Date:  04 MAY 2017                                                                                                   
All three of the phase 3 studies described above demonstrated that treatment with A-101 
(hydrogen peroxide) Topical Solution 40% was both effective and well-tolerated for the 
treatment of subjects with multiple seborrheic keratosis lesions of the trunk, extremities, and 
face.   
3. 
STUDY RATIONALE AND OBJECTIVES 
3.1. 
Rationale 
The rationale for this study is to assess safety and efficacy of A-101 45% A-101 40% and 
Vehicle when applied to 4 Target Lesions on the trunk, extremities and face.  For each subject, at 
least 1 Target Lesion must be on the face and at least 1 Target Lesion must be on the trunk or 
extremities. 
 
Aclaris recently completed three phase 3 clinical studies (301, 302, and 303) that demonstrated 
that A-101 40% is both safe and effective in treating subjects with seborrheic keratosis lesions on 
the face, trunk and extremities.  In addition, a randomized phase 2 study in subjects with 
common warts in which A-101 40% was compared to A-101 45% was completed.  This study 
demonstrated that the higher concentration of A-101 45% was not only effective at treating 
subjects with a common wart but it also demonstrated that there was no increase in local skin 
reactions with the higher concentration.  The results from these 4 clinical trials warrants further 
exploration of A-101 45% in subjects with SK lesions.   
 
3.2. 
Study Objectives 
3.2.1. 
Primary Objective 
The primary objective of this study is to evaluate the safety and effectiveness of A-101 45% 
compared to A-101 40% and each active treatment arm to Vehicle for the treatment of 4 
seborrheic keratosis (SK) Target Lesions on the trunk, extremities and face. For each subject, at 
least 1 Target Lesion must be on the face and at least 1 Target Lesion must be on the trunk or 
extremities. 
3.2.2. 
Secondary Objective 
The secondary objectives of this study include: 
• Duration of response 
• Safety of A-101 
4. 
STUDY DESIGN 
This is a phase 2, randomized, multi-center, study designed to evaluate the safety and efficacy of 
A-101 45% compared to A-101 40% and each active treatment arm to Vehicle in subjects with 
seborrheic keratosis lesions.   
 
During the study, the investigator will identify 4 eligible SK Target Lesions on each subject on 
the trunk, extremities and face.  For each subject, at least 1 SK Target Lesion must be on the face 
and at least 1 Target Lesion must be on the trunk or extremities.  The Target Lesions will be 
treated at a maximum of two treatment visits.  
 


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Date:  04 MAY 2017                                                                                                   
Subjects will be required to complete a total of 8 study visits.  The protocol defined study visits 
are: 
• Visit 1 (Day -13 to 0) Screening 
• Visit 2 (Day 1) Subject randomization and study drug application 
• Visit 3 (Day 8) Target Lesion assessment 
• Visit 4 (Day 22) Target Lesion assessment and if a Target Lesion meets the retreatment 
criteria the subject will receive a second study drug application 
• Visit 5 (Day 29) Target Lesion assessment 
• Visit 6 (Day 50) Target Lesion assessment 
• Visit 7 (Day 78) Target Lesion assessment 
• Visit 8 (Day 106) Target Lesion assessment and end of study visit 
 
Refer to Section 6 or a complete list of protocol required study assessments.   
 
A completed evaluable subject is a subject that completes all required treatment Visits (Visit 1 
and Visit 4), completes Visit 8 (end of study visit), has had all Target Lesions assessed at these 
visits and has not had a protocol violation documented during the study 
4.1. 
Number of Subjects and Study Centers 
Approximately 250 evaluable subjects will be randomized to one of three treatment arms at 
approximately 9 investigational centers in the US. 
 
4.2. 
Duration of Study 
The anticipated time for study enrollment is 4 months. The duration of study participation is 
anticipated to be a maximum of 124 days per subject. Subjects will have a total of 8 study visits.   
The maximum anticipated duration for the study is approximately 8 months. 
 
5. 
STUDY ENTRY CRITERIA 
5.1. 
Inclusion Criteria 
Subjects must meet all of the following criteria to be considered for participation in this study.   
1. Subject is able to comprehend and is willing to sign an informed consent for participation 
in this study. 
2. Male or female ≥ 18 years old. 
3. Subject has a clinical diagnosis of stable clinically typical seborrheic keratosis. 
4. Subject has 4 appropriate seborrheic keratosis Target Lesions on the trunk, extremities 
and face, with at least 1 Target Lesion on the face and at least 1 Target Lesion on the 
trunk or extremities. The 4 identified Target Lesions must meet the requirements as 
defined below: 
a. Have a clinically typical appearance 
b. Have a Physician's Lesion Assessment of ≥ 2 
c. Length that is ≥ 5mm and ≤ 15mm 
d. Width that is ≥ 5mm and ≤ 15 mm 
e. Thickness that is ≤ 2mm 


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Date:  04 MAY 2017                                                                                                   
f. Be a discrete lesion 
g. Be the only SK lesion present when centered in the area outlined by the provided 
circular template 
h. Not be covered with hair which, the in the investigator’s opinion, would interfere 
with the study medication treatment or the study evaluations 
i. Not be in the intertriginous fold 
j. Not be on the eyelids 
k. Not be within 5mm of the orbital rim 
l. Not be pedunculated  
5. Subject chemistry and complete blood count results are within normal limits. If any of the 
laboratory values are outside normal range, the treating investigator must assess the 
value/s as NOT clinically significant and document this in the patient’s medical chart in 
order for the subject to be eligible for randomization.   
6. Woman of childbearing potential must have a negative urine pregnancy test within 14 
days of the first application of study drug and agree to use an active method of birth 
control for the duration of the study.  
7. Subject is non-pregnant and non-lactating. 
8. 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 any Target 
Lesion or which exposes the subject to an unacceptable risk by study participation.   
9. Subject is willing and able to follow all study instructions and to attend all study visits.  
5.2. 
Exclusion Criteria 
Subjects are excluded from this study if any 1 or more of the following criteria is met: 
1. Subject has clinically atypical and /or rapidly growing seborrheic keratosis lesions. 
2. Subject has presence of multiple eruptive seborrheic keratosis lesions (Sign of Lesser -
Trelat). 
3. Subject has current systemic malignancy. 
4. Subject has used any of the following systemic therapies within the specified period prior 
to Visit 1: 
• Retinoids; 180 days 
• Corticosteriods; 28 days 
• Anti-metabolites (e.g., methotrexate); 28 days 
5. Subject has used any of the following topical therapies within the specified period prior 
to Visit 1 on, or in a proximity to any Target Lesion, 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], 
photo-dynamic therapy [PDT]; 180 days 
• Liquid nitrogen, electrodesiccation, curettage, imiquimod, 5-FU, or ingenol 
mebutate; 60 days 
• Hydrogen peroxide: 90 days 
• Retinoids; 28 days 
• Microdermabrasion or superficial chemical peels; 14 days 
• Corticosteriods or antibiotics; 14 days 
6. Subject would require the use of any topical treatment (e.g. moisturizers, sunscreen) to 
any of the Target Lesions 12 hours prior to any study visit.   


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Date:  04 MAY 2017                                                                                                   
7. Subject currently has or has had any of the following within the specified period prior to 
Visit 1 on or in a proximity to any Target Lesion 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 
• Body art (e.g. tattoos, piercing, etc.); currently 
• Excessive tan; currently.  The use of self-tanning lotions/sprays are prohibited. 
8. Subject has a history of sensitivity to any of the ingredients in the study medications. 
9. Subject has any current skin disease (e.g., psoriasis, atopic dermatitis, eczema, sun 
damage), or condition (e.g., sunburn, excessive hair, open wounds) that, in the opinion of 
the investigator, might put the subject at undue risk by study participation or interfere 
with the study conduct or evaluations.  
10. Participation in another therapeutic investigational drug trial in which administration of 
an investigational study medication occurred with 30 days prior to Visit 1.  
 
5.3. 
Removal of Patients from Study Therapy 
A subject may be removed from the study therapy for a variety of reasons, including: 
• Unacceptable adverse event 
• Subject unwilling or refusal to continue with the protocol defined study visits and/or 
consent withdrawal for study participation 
• Change in compliance with an inclusion/exclusion criteria 
• Use of a prohibited medication during the treatment period (through Visit 5) 
• Pregnancy 
• 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. study monitor or 
designee must be informed with 24 hours of the decision to remove the subject from the 
study.   
 
The study may be discontinued at the discretion of Aclaris Therapeutics, Inc.  Some 
examples of reasons for discontinuation are the occurrence of the following:   
• Increased frequency, severity or duration of known AEs 
• Medical, regulatory or ethical reasons affecting the continued performance of the 
study 
• Difficulties in the recruitment of subjects. 
   


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Date:  04 MAY 2017                                                                                                   
5.4. 
Withdrawal Procedures 
If a subject withdraws from the study prior to Visit 8, the reason for and the date of withdrawal 
from the study must be recorded on the eCRF.  If the reason for withdrawal is an adverse event 
or a clinically significant abnormal laboratory test result, monitoring of the subject will continue 
until the event has resolved or stabilized, until the patient is referred to the care of a local health 
care professional, or until a determination of a cause unrelated to the study drug or study 
procedure is made.   
5.5. 
Subject Replacement 
If a subject is randomized to the study but does not receive a dose of study drug, then the subject 
will be replaced.   
 
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.   
5.6. 
Subject Identifier (SI) 
The investigator or designee will assign a unique five-digit subject identifier (SI) to each subject 
at Visit 1.  
 
The SI format will be NN-NNN where the first 2 digits are the investigational center site number 
(using leading zeroes, as appropriate). The final 3 digits are the subject number and must be 
assigned in ascending numerical order, without omitting or repeating any number, starting with 
001 at each investigational center. For example, the SI for the second subject that signs an 
informed consent at site number 04 would be 04-002.  
 
The subject will be identified using the SI in all study documentation for the duration of the 
study. 
 
6. 
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 1.  A written, signed informed consent form (ICF) must be obtained from each 
subject prior to performing any study related procedure (e.g., vital signs, clinical laboratory 
sampling, urine pregnancy test or photography).   


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Date:  04 MAY 2017                                                                                                   
Table 1: 
 Study Procedures 
Visit  
V1 
Screening 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
 
Treatment Day 
-13 to 0 
1 
8 
22 
29 
50 
78 
106 
 Treatment Window 
N/A 
N/A 
+7 days 
+ 4 days 
+ 7 days 
± 7days 
± 7 days 
± 7 days 
Study Procedures 
 
Informed Consent 
X 
 
 
 
 
 
 
 
Inclusion Criteria/Exclusion Criteria 
X 
X1 
 
 
 
 
 
 
Subject Identifier 
X2 
 
 
 
 
 
 
 
Medical history/demographics 
X 
 
 
 
 
 
 
 
Fitzpatrick Skin Type Assessment 
X3 
 
 
 
 
 
 
 
Vital Signs 
X4 
X 
 
 
 
 
 
X 
Prior Medications/Therapies 
X5 
 
 
 
 
 
 
 
Clinical Chemistry and CBC6 
X 
 
 
 
 
 
 
X 
Urine Pregnancy Test7 
X 
X 
 
 
 
 
 
X 
Target Lesion Identification8 
X 
 
 
 
 
 
 
 
Physician’s Lesion Assessment9 
X 
X 
 
X 
 
X 
X 
X 
Lesion Dimensions10 
X 
X 
 
 
 
 
 
 
Standardized Photography11 
X 
X 
 
X 
 
X 
X 
X 
Subject Randomization 
 
X12 
 
 
 
 
 
 
Local Skin Reactions 
 
X13 
X 
X13 
X 
X 
X 
X 
Study Medication Application 
 
X 
 
X14 
 
 
 
 
Subject Instructions 
 
X 
X 
X 
X 
X 
X 
X 
X 
Subject Satisfaction Questionnaire15 
 
 
 
 
 
 
 
X 
Concomitant therapies16 
 
X 
X 
X 
X 
X 
X 
X 
Adverse Events17 
 
X 
X 
X 
X 
X 
 
 
1Subject inclusion/exclusion criteria will be re-assessed prior to randomization during Visit 2.  
2Investigational sites will assign a unique five-digit subject identifier to each subject at Visit 1. This subject identifier will be used in all study documentation for 
the duration of the study.   
3Each subject’s skin must be assessed during Visit 1 using the Fitzpatrick Skin Type Assessment. Refer to Section 9.5.1 for the scale.  
4Vital signs [including temperature, pulse, respiratory rate, blood pressure, height and weight (Visit 1 only)] will be measured by a qualified staff member at Visit 
1, Visit 2 prior to randomization, and at Visit 8.   
5Prior medications/therapies will be collected for a time-period of 13 days prior to Visit 2.  Refer to Section 7.8 for a list of permitted and restricted concomitant 
medications.    


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Date:  04 MAY 2017                                                                                                   
6A complete blood count (including hematocrit, hemoglobin, platelet count, red blood cell count and morphology, white blood cell count and differential 
(absolute and %) including basophils, eosinophils, lymphocytes, monocytes and neutrophils and a clinical chemistry panel including albumin, alkaline 
phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), bicarbonate, calcium, chloride, creatinine, glucose, 
lactate dehydrogenase (LDH), phosphorus, potassium, sodium, total bilirubin, total protein, and uric acid.   
7 Woman of child bearing potential will be required to have a urine pregnancy test at Visit 1, at Visit 2 prior to randomization and at Visit 8. 
8The treating investigator will identify 4 Target Lesions on the trunk, extremities, and face for each subject.  Subjects must have at least 1 Target lesion on the 
face and at least 1 Target Lesion on the trunk or extremities.   
9 The investigator will use the Physician’s Lesion Assessment (PLA) to assess the severity of each Target Lesion.  At Visit 2 and if applicable at Visit 4, the 
investigator must assess the Target Lesions prior to application of the study medication.  In order to be eligible for randomization at Visit 2, the subject must have 
a PLA grade ≥ 2.   
10 The investigator will measure the dimensions of the Target Lesions at Visit 1 and prior to randomization at Visit 2.  In order for the subject to be randomized at 
Visit each Target Lesion must have the following dimensions:  length that is ≥ 5 mm and ≤ 15 mm and width that is ≥ 5 mm and ≤ 15 mm. Additional Target 
Lesion requirements are outlined in Section 8.1.3.    
11 At Visits 1, Visit 2 (prior to study medication application), Visit 4 prior to study medication application if applicable, Visit 6, Visit 7 and at Visit 8, a qualified 
investigational center staff member will take a photograph of each Target Lesion using the Aclaris supplied camera.  All photographs will be sent to a central 
imaging laboratory.   
12 Subjects will be randomized at Visit 2 prior to application of study medication.  Investigational study staff will re-confirm subject eligibility prior to 
randomization.   
13 Both the investigator and the subject will assess each Target Lesion for symptoms associated with irritation.  At Visit 2 and Visit 4, the investigator will assess 
the Target Lesions prior to application of the study medication and 20 (± 4) minutes after treatment with the study medication. At Visits 3 and 5-8, the 
investigator will assess each Target Lesion and report the severity for all signs.  At Visit 2 and Visit 4, the subject will assess the Target Lesions prior to 
application of the study medication and 10 (±4) minutes after the treatment of the study medication.   At Visits 3 and 5-8, the subject will assess each Target 
Lesion and report the average severity over the previous 24 hours for all symptoms.  Refer to Section 9.1 for the complete list of Local Skin Reaction signs and 
symptoms.   
14Study medication will be applied by a member of the investigational study staff that has been trained on the protocol.    All Target Lesions will be treated with 
study medication following randomization at Visit 2.  If a Target Lesion meets the criteria for re-treatment as defined in Section 7.5 the lesion will be re-treated 
at Visit 4.  Following application of study medication, subjects must NOT wash/submerge the Target Lesions for at least 6 hours and they must NOT apply any 
topical products to the Target Lesions for at least 6 hours.   
15Subjects will be asked to assess how satisfied they are with the treatment they received to each Target Lesion.  This questionnaire assessment will take place at 
Visit 8 only.   
16All concomitant therapies including (topical and oral) prescription medications, over the counter medications and natural supplements and non-drug therapies 
including chiropractic, physical therapy, and energy based therapy must be documented in the subject CRF.  Subjects must not apply any topical products (e.g. 
moisturizers, sunscreen, etc.) to their Target Lesions within 12 hours prior to any study visit.   
17The reporting period for Serious Adverse Events (SAEs) begins when the subject signs the informed consent and continues through Visit 6.  Refer to Section 
10.1.2 for instructions on the reporting of SAEs.  Non-serious clinical adverse events will be collected following the application of the study medication at Visit 
2. Non-serious adverse events that occur between the time of consent and study medication application will be documented as medical history.   All safety 
reporting (AEs and SAEs) will conclude at Visit 6 (approximately 21 days after last study medication application) except for clinical adverse events related to 
local skin reactions.  These events will be collected through V8.    


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Date:  04 MAY 2017                                                                                                   
7. 
STUDY TREATMENT 
7.1. 
Investigational Study Medication 
The study medications for the study are A-101 40%, A-101 45%, and matching Vehicle.  All 
study medications are solutions that are water-clear, colorless solutions which are 
indistinguishable in physical appearance.   
 
Table 2 
Study Medication Information 
Study Medication 
Name 
A-101 40% 
A-101 45% 
Vehicle 
Manufacturer 
James Alexander Corporation, Blairstown NJ 
A-101 concentration 
(%) 
40 
45 
0 
Pharmaceutical Form 
Solution 
Storage Conditions 
59ºF to 77ºF (15ºC to 25ºC) protected from light, excessive heat, open 
flame and combustibles, out of direct sunlight and in a well-ventilated, 
dry area* 
Dose Regimen 
 
Route 
Topical 
Application 
Safety glasses and nitrile or vinyl examination gloves must be worn 
during the application process.  Latex gloves are prohibited.   
Duration of 
Administration 
Apply study medication to each Target Lesion for approximately 20 
seconds.  Allow each Target Lesion to remain undisturbed for 
approximately 60 seconds.  Repeat the application/waiting cycle until 
the study medication has been applied to each Target Lesion  up to 4 
times.  Subjects may receive up to 2 treatments (Visit 2 and Visit 4) 
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.   
 
7.2. 
Subject randomization  
Prior to the start of the study, Aclaris Therapeutics, Inc./designee will generate a randomization 
list that will be provided to the assigned clinical packaging organization for study medication 
labeling.   
 
The randomization list will be stored with limited access to designated personnel for study 
medication labeling.      
 
Subjects will be randomized to the study in a 1:2:2 ratio.  Subjects will be randomized at Visit 2 
following re-confirmation of subject eligibility.   
 


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Date:  04 MAY 2017                                                                                                   
7.3. 
Study medication packaging, storage and dispensing 
A-101 45%, A-101 40% and matching Vehicle will be provided by Aclaris Therapeutics, Inc. 
and labelled according to the local law and legislation.   
 
The study medication will be packaged in single use applicators..  Each single-use applicator 
consists of a crushable glass ampoule that contains 2.2 milliliters (mL) of study medication that 
provides for at least 1.3 mL of study medication available for treatment.  The ampoule is 
provided inside a sealed polyethylene tube with a flocked, doe foot applicator on one end.   
 
One subject kit box contains 3-single use study medication applicators.  Each kit will be labelled 
with a two part, three panel, double blind label.  One part (one-panel) of the label remains 
attached to the Subject Kit, the other part (two-panel tear-off) is separated and attached to the 
subject’s Label Page CRF when the subject is randomized.   
 
A-101 study medication must be stored in a location where there is limited access to the 
investigational study medication at 59ºF to 77ºF (15ºC to 25ºC) protected from light, excessive 
heat, open flame and combustibles, out of direct sunlight and in a well-ventilated, dry area.   
 
Investigational study medication supplies are only to be used for subjects properly consented and 
enrolled to this study.   
 
7.4. 
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 study monitor at the completion of the study 
and all unused study medication will be returned to Aclaris Therapeutics, Inc. drug depot for 
disposal per Aclaris Therapeutics, Inc. (or designee’s) written instructions. 
 
 
7.5. 
Study Medication Treatment 
The study medications are for external, topical use on the Target Lesions on the appropriate 
study subject only.  
 
The investigational center staff member performing the study medication treatments must 
comply with the study medication storage conditions outlined in Section 7.1.  A trained 
healthcare professional may apply study medication to subjects randomized to the study.   


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Date:  04 MAY 2017                                                                                                   
 
At Visit 2, the staff member who has been trained on the application process for the A-101 
solution medication will perform an initial study medication treatment for each Target Lesion.  
 
At Visit 4, any Target Lesion that has a PLA grade of >0 and ONLY Target Lesions that have 
a PLA grade of >0, must receive study medication treatment UNLESS either of the following 
criteria apply to the Target Lesion: 
• The Target Lesion has a Visit 4 pre-treatment LSR grade of 3 (severe) for any sign or 
symptom AND the grade has increased compared to the Visit 3 
• The Target Lesion is, in the investigator’s opinion, not appropriate for a retreatment (the 
investigator must note the reason on the subject’s Comments CRF page). 
 
7.5.1. 
Preparing the Study Medication for Application 
To perform a study medication treatment for a Target Lesion a staff member will select the 
appropriate study medication applicator. The following instructions outline the procedure for 
application of the study medication to the Target Lesions:  
• Prepare for the treatment: 
o Wash your hands prior to, and after completing the study medication treatments  
o Wear safety glasses and nitrile or vinyl examination gloves during the treatment; 
latex gloves are prohibited 
o Select the applicator with the lowest available number   
o Complete the study medication applicator label as instructed  
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 treatment process as outlined in Figure 1. 
 
Seborrheic Keratosis Target Lesions 
should be cleaned using an alcohol wipe 
prior to application of A-101 Solution or 
matching Vehicle Solution.   
 
 


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Date:  04 MAY 2017                                                                                                   
 
 
Step 1:  Hold the Study Medication    Step 2:  Crush the ampule in the 
applicator so that the applicator          applicator by applying pressure at  
cap is pointing up.                               the center of the barrel of the applicator. 
 
 
Step 3:  Remove the sleeve.         Step 4: Tap the barrel of the applicator 
                                                     to ensure the solution is free of the 
                                                      crushed ampule.     


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Date:  04 MAY 2017                                                                                                   
 
 
 
Step 5:  Gently remove the cap        Step 6:  Express a single drop of 
by twisting while pulling away        the Study Medication Topical Solution  
from the applicator.                          so that the tip of the applicator becomes wet. 
 
Step 7: Apply the solution to the  
Lesion in a circular motion. 
 
Figure 1:   Diagram Showing the Process for Preparing and Applying A-101 Study 
Medication  
7.5.2. 
Applying Study Medication to Trunk/Extremities 
To apply the study medication to a Target Lesion on the TRUNK AND EXTREMITIES the 
staff member will follow these treatment instructions:  
• Do not apply the study medications to eyes, nose, mouth, mucous membranes, or open 
wounds 
• Position the subject with the plane of the Target Lesion to minimize exposure of the skin 
surrounding the Target Lesion to the study medication  
• Thoroughly cleanse the Target Lesion by firmly rubbing with a swab/wipe wetted with 
70% isopropyl alcohol 
• Using firm pressure, squeezing in the middle of the applicator, apply one drop of study 
medication onto the SK lesion and then move applicator around in a circular motion to 
fully saturate the lesion.  Apply the study medication for approximately 20 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 


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Date:  04 MAY 2017                                                                                                   
• Ensure the Target Lesion is fully saturated with study medication at the end of the ~20 
second application 
• Allow the Target Lesion to remain undisturbed for ~60 seconds 
• After ~60 seconds repeat the ~20 second application process 
• Repeat the application/waiting cycle until the study medication has been applied to the 
Target Lesion up to 4 times. 
 
7.5.3. 
Applying Study Medication to the Face 
To apply the study medication to Target Lesions on the FACE the staff member will follow 
these treatment instructions: 
• Do not apply the study medications to eyes, mouth, mucous membranes, open wounds 
• Do not apply the study medication to the eyelids or within 5 mm of the orbital rim 
• If, in the investigator’s opinion it is needed to ensure no study medication enters the eye: 
o Position the subject in the supine position with the head slightly elevated and 
angled such that any excess study medication will flow away from the eye. 
o Aclaris Therapeutics will supply sites supplies of white petrolatum (100%) United 
States Pharmacopeia (USP) that is to be applied along the orbital rim and at the 
medial and lateral canthi; gently stretch the periorbital skin between the thumb 
and forefinger at the time of petrolatum application to distend any periorbital 
rhytides (e.g., “crow’s feet”) and ensure full coverage of the skin at the base of 
the rhytides to decrease the likelihood of tracking of the study medication 
towards the eye 
o Have the subject hold an absorbent pad in the appropriate area of the eye to 
absorb any excess study medication that might track away from the Target 
Lesion 
o Instruct the subject to keep both eyes closed during the entire study medication 
treatment procedure 
• After the subject is properly prepared and positioned, thoroughly cleanse the Target 
Lesion by firmly rubbing with a swab/wipe wetted with 70% isopropyl alcohol 
• Using firm pressure, squeezing in the middle of the applicator, apply one drop of study 
medication onto the SK lesion and then move applicator around in a circular motion to 
fully saturate the lesion.  Apply the study medication for approximately 20 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 Target Lesion is wet with study medication at the end of the ~20 second 
application 
• Allow the Target Lesion to remain undisturbed for ~60 seconds 
• After ~60 seconds repeat the ~20 second application process 
• Repeat the application/waiting cycle until the study medication has been applied to the 
Target Lesion up to 4 times. 
 
Repeat the treatment procedure that is appropriate for the body location (i.e., trunk and 
extremities or face) until all Target Lesions that require treatment have been treated. 
 


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Date:  04 MAY 2017                                                                                                   
Record the time the final treatment is completed for the last treated Target Lesion as the 
Treatment Completion Time.  
 
It is acceptable to treat multiple Target Lesions at the same time if, in the investigator’s opinion, 
it is practical without exposing non-lesional skin to the study medication. 
 
After completing the study medication treatment to the Target Lesion do not disturb the Target 
Lesion until just prior to the subject’s post-treatment LSR evaluation.   
 
Just prior to the subject’s post-treatment LSR evaluation absorb any remaining study medication 
and gently dab or otherwise dry the Target Lesion with an absorbent pad or dry gauze without 
wiping or rubbing.   
 
7.6. 
Video Recording of Study Medication Application 
At one identified investigational site, a group of subjects will have the application of their A-101 
study medication video recorded.  The video recording will be performed during Visit 2 (Day 1) 
and will be done by a third-party imaging vendor.  Up to 15 randomized subjects will be 
consented to allow for the video recording of the application of their A-101 study medication. 
Subjects will be de-identified by the imaging vendor and these video recordings will be stored by 
the third party vendor until the end of the study.   
 
These video recordings will be used by Aclaris to develop a training video for physicians on the 
proper application technique  utilizing the  A-101 Topical Solution applicator.   
 
 
7.7. 
Dose modification 
If a subject refuses to allow a study medication initial treatment or retreatment the investigator 
must report the visit number, visit date, Target Lesion number(s) the subject refused to allow 
treatment for and the reason for the refusal 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.  
 
The subject must have the Visit 2 initial study medication treatment to all Target Lesions to 
remain in the study.  
 
The subject does not need to be removed from the study based solely on her/his refusal to have a 
study medication retreatment at Visit 4.  
 


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Date:  04 MAY 2017                                                                                                   
7.8. 
Previous and Concomitant Therapies 
7.8.1. 
Previous therapies 
During Visit 1, the investigator or designee will question the subject to ensure they have not used 
any excluded therapies (Section 7.8.3). 
 
7.8.2. 
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. 
 
7.8.3. 
Prohibited therapies 
During the course of this study, subjects are prohibited from using the following treatment 
therapies to treat any of the Target Lesions: 
 
• Retinoids (systemic or topical) 
• Corticosteriods (systemic or topical)  
• Antimetabolites 
• LASER, light or other energy based therapy 
• Liquid nitrogen, electrodesiccation, curettage, imiquimod, ingenol mebutate 
• Microdermabrasion or superficial chemical peels 
• Antibiotics (topical)    
• Self-tanner lotions and sprays 
  
The investigator should notify the Medical Monitor immediately if any prohibited therapies are 
required to ensure subject safety. 
 
Starting with Visit 2, subjects must not apply any topical products (e.g., moisturizers, sunscreens, 
etc.) to their Target Lesions within 12 hours prior to any study visit (Note: routine cleansing 
products are allowed). 
 
After the completion of any study visit where a study medication treatment was performed 
subjects must NOT wash/submerge the Target Lesions for at least 6 hours and must not apply 
any topical products to the Target Lesions for at least 6 hours. 
 


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Date:  04 MAY 2017                                                                                                   
7.9. 
Breaking the Blind 
The blind may be broken ONLY in the event of a medical emergency, in which knowledge of the 
study medication identity is critical to the management of the subject’s course of treatment.  
Before breaking the blind the investigator should determine that the information is necessary.  In 
many cases, particularly when the emergency is clearly not study medication-related, the 
problem may be effectively managed by assuming that the subject is receiving an active study 
medication without the need for unblinding.   
 
If deemed necessary to break the blind for a study subject, attempt to contact the Medical 
Monitor to obtain permission to break the blind of a particular subject.  If it is not possible to 
contact the Medical Monitor beforehand, contact her/him as soon as possible after breaking the 
blind for a subject.  
 
To identify a subject’s study medication, locate the second panel of the tear-off label from the 
Subject Kit attached to the subject’s Label Page CRF and follow the instructions on the label.  
Record the date of un-blinding, the reason for the un-blinding and the initials of investigational 
center staff member who performed the un-blinding on the subject’s Label Page CRF.   
 
At the end of the study, the original Label Page CRFs will be returned to Aclaris Therapeutics 
with a photocopy placed in the investigator’s study file.  The original Label Page CRFs will be 
available, upon request, to the site if needed to respond to a regulatory inspection.   
 
8. 
ASSESSMENTS OF CLINICAL EFFICACY 
The investigator performing these evaluations must not participate in the study medication 
treatment for the subject being evaluated.  
 
Similar lighting conditions and subject positioning should be used for all evaluations for a given 
subject. 
 
8.1. 
Target Lesion Identification 
At Visit 1, the investigator will identify 4 Target Lesions on the trunk, extremities and face for 
each subject for treatment and evaluation. For each subject, at least 1 Target Lesion must be on 
the face and at least 1 Target Lesions must be on the trunk or extremities. 
 
For this study, the trunk, extremities and face are defined as: 
• Trunk: 
o The front and back of the torso, including the neck (below the mandibular ridge 
on the front of the torso and below the hairline on the back of the torso), 
vertically down to the beltline 
• Extremities: 
o Arms: 
 From the shoulder to the tips of the fingers, including the back of the 
hands, excluding the palms 
o Legs: 


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Date:  04 MAY 2017                                                                                                   
 From the hip to the tips of the toes, including the top of the feet, excluding 
the soles.  
• Face: 
o Vertically from the mandibular ridge vertically up to the hairline (for subjects 
with a receded hairline the hairline is defined by the vertical line drawn coronally 
from tragus to tragus) 
o Horizontally from tragus to tragus, excluding the eyelids and areas within 5mm of 
the orbital rim.  
 
At Visit 1, each Target Lesion must: 
• Have a clinically typical appearance    
• Have a PLA of ≥2  
• Have a length that is ≥5mm and ≤15mm  
• Have a width that is ≥5mm and ≤15mm 
• Have a thickness that is ≤2mm      
• Be a discrete lesion    
• Be, when centered in the area outlined by the provided circular template,  the only SK 
lesion present    
• Not be covered with hair which, in the investigator’s opinion, would interfere with the 
study medication treatment or the study evaluations (NB: the study medication may 
bleach hair) 
• Not be in an intertriginous fold    
• Not be on the eyelids 
• Not be within 5mm of the orbital rim 
• Not be pedunculated. 
 
The groin areas and the inframammary fold, where, in the investigator’s opinion, the Target 
Lesion might be occluded, are excluded from the treatment area. 
 
Record the approximate location of each Target Lesion on the appropriate body chart in the 
CRFs. Also, identify the body area (i.e., face, trunk, arm, leg) for each Target Lesion in the 
CRFs. Number the Target Lesions starting with 1 and proceeding up to 4 with no number 
omitted or reused. 
 
Aclaris Therapeutics will provide the investigational site with standard circular templates and 
colored stickers that are to be used to identify the Target Lesions.   
 
At Visit 1, the investigator and an investigational staff member will identify the Target Lesions 
by placing 2 appropriately colored stickers approximately 180 degrees opposite each other with 
the Target Lesion in the center of the area outlined by the provided circular template (Refer to 
Figure 2.  Figure not to scale):    


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Date:  04 MAY 2017                                                                                                   
 
                                                  
                                                                      ID Sticker 
                                                   
 
 
 
                                                                                                           23mm diameter template cutout  
                               Target Lesion                                                            
  
 
 
 
 
 
                                                                       
 
 
 
 
 
 
 
                                                                       ID Sticker  
Figure 2 
Target Lesion Identification 
 
Write the Target Lesion number on one of the identification (ID) stickers. The ID stickers must 
be visible in the study photographs (Section 9.5.2). The Target Lesion #/ID sticker color 
relationships are: 
• Target Lesion #1/white ID stickers 
• Target Lesion #2/yellow ID stickers 
• Target Lesion #3/green ID stickers 
• Target Lesion #4/blue ID stickers. 
 
At Visits 2-8, an investigational staff member will confirm the location of each Target Lesion 
using an appropriate combination of the Visit 1 hard-copy reference prints, Visit 2 photographs 
and the body charts. The staff member will identify the Target Lesion by placing 2 appropriately 
colored ID stickers, with the Target Lesion number written on one sticker, approximately 180 
degrees opposite each other with the Target Lesion in the center of area outlined by the provided 
circular template.  
8.1.1. 
Standardized photography 
At Visits 1, 2, 4, 6, 7 and 8 qualified investigational center staff member will take standardized 
color photographs of each Target Lesion.  
 
The photographs are to document the location of the Target Lesion and to assist with relocating 
the Target Lesion and the Target Lesion ID stickers must be visible in the photographs.  The 
subject’s identity will not be revealed in the study photographs. 
 
At Visit 2, the photographs must be taken prior to the study medication treatment. 
Care must be taken to ensure the same lighting, background, subject positioning relative to the 
camera and camera settings are used for each photograph.  
 


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Date:  04 MAY 2017                                                                                                   
Sites will be provided with photography equipment and supplies necessary for obtaining the 
Target Lesion photographs.  Detailed instructions for obtaining and managing the photographs 
will be documented in the study specific Photography Manual and provided to the site at the 
study initiation visit.    
8.1.2. 
Physician’s Lesion Assessment (PLA) 
The PLA is the investigator’s assessment of the severity of the Target Lesion at a particular time 
point. The investigator should NOT refer to any other assessments to assist with these assessments.  
 
 
At Visits 1, 2, 4, 6, 7 and 8, the investigator will assess the Target Lesion using the scale below and 
report the one integer that best describes the severity of the Target Lesion. At Visit 2, and if 
appropriate Visit 4, the investigator must complete the PLA prior to the study medication 
treatment. 
 
Table 3 Physician’s Lesion Assessment Definitions 
 
Physician’s Lesion Assessment 
Grade Descriptor 
0 
Clear: no visible seborrheic keratosis lesion 
1 
Near Clear: a visible seborrheic keratosis lesion with a surface appearance different 
from the surrounding skin (not elevated) 
2 
Thin: a visible seborrheic keratosis lesion (thickness ≤1mm) 
3 
Thick: a visible seborrheic keratosis lesion (thickness >1mm) 
 
All investigational site staff will receive training on the PLA Assessment Scale and be provided 
with a PLA Assessment Manual (refer to Appendix 15.2) that will be used as a reference tool during 
the conduct of the study.    
 
In order for a subject to be eligible for screening and randomization to the study, each Target Lesion 
must have a PLA grade of ≥ 2.   
 
8.1.3. 
Lesion Dimensions 
At Visit 1 and at Visit 2 prior to randomization the investigator will measure the length and the 
width of each Target Lesion using the ruler provided.  
 
The investigator must measure the length and width of each Target Lesion in millimeters (mm) as 
follows: 
• 
Length (i.e., the length of the longest axis) reported to the nearest mm 
• 
Width (i.e., the length of the longest axis perpendicular to the length) reported to the 
nearest mm. 
• 
Thickness (height above the surrounding skin) 
 
At Visit 1 for the subject to be enrolled and at Visit 2 for the subject to be randomized each Target 
Lesion must have: 


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Date:  04 MAY 2017                                                                                                   
• A Length that is ≥5mm and ≤15mm 
• A Width that is ≥5mm and ≤15mm. 
• A Thickness that is ≤ 2 mm.   
 
At Visit 2, the length and width must be measured prior to any study medication treatment. 
 
At Visits 1, 2, 4, 6, 7 and 8 the investigator must measure the thickness (height) of each Target 
Lesion above the surrounding skin, in mm using the ruler provided as part of the PLA 
assessment. 
 
At Visit 1 for the subject to be enrolled, each Target Lesion must have a thickness that is ≤2.0mm.  
8.2. 
Subject Instructions 
An investigational center staff member will dispense a Subject Instruction Sheet to each subject 
at Visit 1 (Refer to Appendix 15.1). 
 
Throughout the study, the subjects should: 
• Continue their routine cleansing regimen except they should avoid vigorous scrubbing of 
the Target Lesions (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 Target Lesions to excessive natural or artificial ultraviolet radiation 
(e.g., sunlight, tanning beds) and use sunscreen on the Target Lesions, if excessive 
exposure cannot be avoided 
• Avoid the use of self-tanning lotions and spray tans. 
• Bring the subject instruction sheet with them to each visit. 
 
On study visit days, the subjects should: 
• When appropriate for the Target Lesion location wear loose fitting clothing to the visit 
(Note: clothing that comes in contact with the study medication may be bleached) 
• Starting with Visit 2, not apply any topical products to the Target Lesions 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 Target Lesions for at least 6 hours 
o Apply any topical products to the Target Lesions for at least 6 hours. 
8.3. 
Subject Satisfaction Survey 
Subjects will be asked to assess their level of satisfaction regarding the study medication 
treatment.  The subject survey will be completed at Visit 8 only.  The subject will be asked to 
answer the following question in relation to the treatment of each Target Lesion: 
 
Which of the following statements best reflects how your level of satisfaction with the 
outcome of your treatment to Target Lesion X? 
  
1. Very Satisfied 


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Date:  04 MAY 2017                                                                                                   
2. Satisfied 
3. Neutral  
4. Dissatisfied 
5. Very Dissatisfied 
 
8.4. 
Other Study Supplies 
Aclaris Therapeutics, Inc. will provide: 
• An appropriate ruler, or other instrument, for measuring the thickness of the Target 
Lesions and the Lesion Dimensions 
• 70% isopropyl alcohol for cleansing the SK Target Lesion during the study medication 
treatment process 
• White Petrolatum USP for protecting sensitive areas during study medication treatments 
for Target Lesions on the face 
• Templates for use when identifying Target Lesions 
• Supplies and instructions for collecting, labeling, shipping and result reporting for the 
clinical laboratory tests and urine pregnancy tests from a third party 
• Equipment, supplies and training for taking standardized photographs 
• Eyewash kits. 
9. 
ASSESSMENT 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. 
 
The investigational staff member performing the LSR evaluations must not participate in the 
study medication treatment for the subject being evaluated. 
 
9.1. 
Local Skin Reactions (LSR) 
The LSR assessment is the investigator’s assessment of the signs and the subject’s assessment of the 
symptoms associated with irritation at each Target Lesion site, which includes the Target Lesion 
and the area immediately surrounding the Target Lesion. The investigator and subject may refer to 
other evaluations (photographs) to assist with these assessments. However, investigators may only 
refer to these evaluations after the PLA has been performed.   
 
Local Skin Reactions: 
• Signs (assessed by the investigator): 
o Erythema 
o Edema 
o Scaling/dryness 
o Vesicles/bullae 
o Crusting 
o Erosion 
o Ulceration 
o Post-inflammatory hyper-pigmentation 


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Date:  04 MAY 2017                                                                                                   
o Post-inflammatory hypo-pigmentation (does not include the superficial transient skin 
blanching/whitening related to the action of the study medications) 
o Atrophy 
o Scarring. 
 
• Symptoms (assessed by the subject): 
o Stinging/burning 
o Pruritus (itch). 
 
At Visits 2-8, the investigator and the subject will evaluate the LSR signs and the LSR symptoms at 
each Target Lesion site respectively.  
 
The investigator will assess the LSR signs as follows: 
• Visits 2 and 4: 
o For each Target Lesion site report the severity for all signs prior to any study 
medication treatment 
o For every treated Target Lesion site, 20 (±4) minutes after the Treatment 
Completion Time, report the severity for the following signs: 
 Erythema 
 Edema 
 Scaling/dryness 
 Vesicles/bullae. 
• Visits 3 and 5-8: 
o For each Target Lesion site, report the severity for all signs. 
 
The subject will assess the LSR symptoms as follows: 
• Visits 2 and 4: 
o For each Target Lesion site report the average of the severity over the previous 24 
hours for all symptoms prior to any study medication treatment 
o For every treated Target Lesion site, 10 (±4) minutes after the Treatment 
Completion Time, report the average of the severity of the LSR for all symptoms 
since completion of the study medication treatment. 
• Visits 3 and 5-8: 
o For each Target Lesion site, report the average of the severity over the previous 
24 hours for all symptoms. 
 
Both the subject and the study staff member will initial and date the source document to indicate 
the subject performed the LSR for symptoms as instructed. The staff member must not influence 
the subject’s assessment. 
 
The investigator should report the one integer that best describes the severity of each LSR sign 
for each Target Lesion site using the scale below. Each subject should report the one integer that 
best describes the severity of each LSR symptom for each Target Lesion site using the scale 
below: 
 


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Date:  04 MAY 2017                                                                                                   
Table 4 
Grading of Local Skin Reactions 
Local Skin Reactions 
Grade 
Descriptor 
0 
None 
1 
Mild 
2 
Moderate 
3  
Severe 
 
9.2. 
Vital signs 
Vital signs will be measured by a qualified staff member at Visit 1, Visit 2 prior to 
randomization, and at Visit 8. The following items will be measured: 
• Body temperature 
• Pulse rate 
• Respiration rate 
• Blood pressure (systolic and diastolic) after the subject sits quietly for at least 5 minutes 
• Height (at Visit 1 only) 
• Weight (at Visit 1 only). 
 
Any measure that is, in the opinion of the investigator, abnormal AND clinically significant (CS 
must be recorded as history if found prior to the first study medication treatment or as an AE if 
found after the first study medication treatment begins (Section 10.1).  
 
A systolic blood pressure >140mm Hg or a diastolic blood pressure >90mm Hg is considered 
abnormal and therefore must be defined as CS or not clinically significant (NCS) on the CRFs.  
9.3. 
Clinical laboratory sampling 
Non-fasting blood samples for clinical laboratory analysis will be collected by a qualified staff 
member at Visit 1 and at Visit 8. Approximately 2 mL of blood will be collected for each 
sample, a total of approximately 4 mL per subject. 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 


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Date:  04 MAY 2017                                                                                                   
Glucose 
    Eosinophils 
Lactate dehydrogenase (LDH) 
    Lymphocytes 
Phosphorus 
    Monocytes 
Potassium 
    Neutrophils 
Sodium 
 
Total bilirubin 
 
Total protein 
 
Uric acid 
 
 
 
The results of the clinical laboratory tests will be reported on the central laboratory’s standard 
reports. These laboratory results will be sent to the investigator via fax.  The investigator must 
review all laboratory reports in a timely manner and note NCS or CS to define the clinical 
relevance of any result that is outside the normal range for the laboratory. The investigator must 
date and initial every laboratory report.  
 
The investigator must review the Visit 1 laboratory results for all the measured analytes for each 
subject prior to Visit 2. The subject must not be randomized at Visit 2 if any of the Visit 1 results 
are outside normal range for the laboratory AND, in the opinion of the investigator, CS. 
 
The investigator must report all laboratory results that are BOTH outside the normal range for 
the laboratory AND, in the opinion of the investigator, CS as medical history if found prior to the 
first study medication treatment or as an AE if found after the first study medication treatment 
begins.  
 
9.4. 
Urine pregnancy tests 
The investigator or designee will perform a urine pregnancy test for subjects who are WOCBP at 
Visit 1, at Visit 2 prior to randomization and at Visit 8.    
 
Subjects who are WOCBP must have a negative pregnancy test result at Visit 1 to continue in the 
study and at Visit 2 to be randomized. 
 
If the result of any post-randomization urine pregnancy test is positive, the subject will be 
withdrawn from the study and the subject’s pregnancy documented and followed as outlined in 
Section 11. 
 
9.5. 
Other Evaluations 
9.5.1. 
Demographics and medical history 
At Visit 1, the investigator or designee will collect demographic information including date of 
birth, sex at birth, race and, if appropriate, ethnicity for each subject.  
 
At Visit 1, the investigator must determine each subject’s Fitzpatrick skin type and document 
appropriately on the subject’s CRF. 
  


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Date:  04 MAY 2017                                                                                                   
Table 5 
Fitzpatrick Skin Type Scoring System 
Skin Type 
Classification 
Description 
Type I 
always burns, never tans (pale white; blond or red 
hair; blue eyes; freckles) 
Type II 
usually burns, tans minimally (white; fair; blond or 
red hair; blue, green, or hazel eyes) 
Type III 
sometimes mild burn, tans uniformly (cream white; 
fair with any hair or eye color) 
Type IV 
burns minimally, always tans well (moderate brown) 
Type V 
very rarely burns, tans very easily (dark brown) 
Type VI 
Never burns, never tans (deeply pigmented dark 
brown to darkest brown) 
(Fitzpatrick 1988) 
 
Medical history information will be recorded including all medical conditions and disease states 
that, at Visit 1: 
• Are ongoing 
• Require concomitant therapy 
• Are, in the opinion of the investigator, relevant to the subject’s study participation. 
 
9.5.2. 
Standardized photography 
At Visits 1, 2, 4, 6, 7 and 8, a qualified investigational center staff member, other than the 
investigator, will take standardized color photographs of each Target Lesion.  
 
The photographs are to document the location of the Target Lesion and to assist with relocating 
the Target Lesion and the Target Lesion ID stickers must be visible in the photographs (Section 
8.1). The subject’s identity will not be revealed in the study photographs. 
 
At Visit 2, the photographs must be taken prior to the study medication treatment. 
Care must be taken to ensure the same lighting, background, subject positioning relative to the 
camera and camera settings are used for each photograph.  
 
Equipment, supplies, training and detailed instructions for obtaining and managing the 
photographs will be provided to the investigational center prior to the initiation of subject 
enrollment.  
 


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Date:  04 MAY 2017                                                                                                   
10. 
ADVERSE EVENTS 
10.1. 
Definitions 
10.1.1. 
Adverse events (AE) 
• An adverse event (AE) is any untoward medical occurrence in a patient that 
develops or worsens in severity during the conduct of a clinical study of a 
pharmaceutical product and does not necessarily have a causal relationship to the 
study drug.  An adverse event can, therefore, be any unfavorable and unintended 
physical sign, symptom, or laboratory parameter that develops or worsens in 
severity during the course of the study, or significant worsening of the disease 
under study (or any concurrent disease), whether or not considered related to the 
study drug.  Accordingly, an adverse event could include any of the following: 
• intercurrent illnesses 
• physical injuries 
• events possibly related to concomitant medication 
• significant worsening (change in nature, severity, or frequency) of the disease 
under study or other pre-existing conditions.  (NOTE: A condition, recorded as 
pre-existing, that is intermittently symptomatic [e.g., headache] and which occurs 
during the study should be recorded as an adverse event.) 
• drug interactions 
• events occurring during diagnostic procedures or any washout phase of the study 
• laboratory or diagnostic test abnormalities occurring after the start of the study 
(i.e., after screening and once confirmed by repeat testing) that results in the 
withdrawal of the patient from the study, requires medical treatment or further 
diagnostic work-up, or is considered by the study investigator to be clinically 
significant.  NOTE: Abnormal laboratory test results at the screening visit that 
preclude a patient from entering the study or receiving study treatment are not 
considered adverse events, but will be recorded to monitor data from patients who 
do not meet screening criteria. 
Worsening of any of the Target Lesion assessments should be reported as an AE ONLY if 
the use of the study medication is interrupted or discontinued or if therapy is required to 
manage the event.  
 
The investigator must, for any Target Lesion 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.  
 


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Date:  04 MAY 2017                                                                                                   
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. 
 
10.1.2. 
Serious adverse event (SAE) 
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. 
 
10.1.3. 
Adverse event reporting period 
The investigator must start reporting non-serious AEs starting with the subject’s first study 
medication treatment continuing until Visit 5. Non-serious adverse events that occur between the 
time the subject was consented and the first application of study medication will be reported as 
medical history.   
 
Reporting for SAEs begins after the subject signs the informed consent and continues until Visit 
6 (regardless of relationship to study medication).  If a subject experiences a SAE after Visit 6 
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.   
 


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Date:  04 MAY 2017                                                                                                   
10.1.4. 
Severity 
The investigator must define the severity of each AE using the following definitions as a 
guideline. The investigator will consider the range of the possible severity of the event and 
identify the severity that is the most appropriate according to her/his medical judgment. 
 
Mild – Awareness of signs or symptom, but easily tolerated 
Moderate – Discomfort, enough to cause interference with usual activity 
Severe – Incapacitating with inability to perform usual activity. 
 
10.1.5. 
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). 
 
10.2. 
Reporting Procedures 
10.2.1. 
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 or designee will monitor the subject for at least 20 minutes after the Treatment 
Completion Time at Visit 2 and at Visit 4 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.  
 


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Date:  04 MAY 2017                                                                                                   
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. 
 
10.2.2. 
Procedure for reporting a serious adverse event 
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 Medical Monitor of the SAE: 
Stuart D. Shanler, MD 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Telephone:  484-321-5555 
Serious Adverse Event Facsimile:  484-324-2359 
Email:  sshanler@aclaristx.com 
 
3. 
Within 24-hours of becoming aware of the event, a SAE report form, an AE CRF and any 
other relevant information (e.g., concomitant medication CRF, medical history CRF, 
laboratory test results) must be faxed to the SAE Fax line listed above. 
4. 
Monitor and document the progress of the SAE until it resolves or, if not resolved after the 
subject’s last study visit, until in the opinion of the investigator the AE reaches a clinically 
stable outcome with or without sequelae AND the investigator and Medical Monitor agree 
that the SAE is satisfactorily resolved. 
5. 
Inform the Medical Monitor of SAE updates by telephone followed by an SAE form 
update sent by fax or by e-mail. 
6. 
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). 
 
10.2.3. 
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 


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Date:  04 MAY 2017                                                                                                   
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. 
11. 
PREGNANCY 
WOCBP include any female who has experienced menarche and who has not undergone 
successful surgical sterilization (e.g., hysterectomy, hysteroscopy, bilateral tubal ligation, 
bilateral oophorectomy or bilateral mini-laparotomy) or is not postmenopausal. Postmenopausal 
is defined as ≥12 months with no menses without an alternative medical cause. Women who are 
WOCBP and are using an active method of birth control, are practicing abstinence or where the 
partner is sterile (e.g., vasectomy), should be considered to be WOCBP. 
  
All WOCBP must use an active method of birth control during the course of the study, in a 
manner such that risk of failure is minimized. Abstinence or having a sterile partner is not an 
active method of birth control. 
 
Prior to trial enrollment, WOCBP must be advised of the importance of avoiding pregnancy 
during trial participation and the potential risk factors for a pregnancy.  The subject must sign an 
informed consent form documenting this discussion.  During the trial, all WOCBP will be 
instructed to contact the investigator immediately if they suspect they might be pregnant (e.g., 
missed or late menstrual period). 
 
If a subject or investigator suspects that the subject may be pregnant prior to study medication 
administration, the study medication must be withheld until the results of a pregnancy test are 
available.  If pregnancy is confirmed, the subject must not receive study medication and must be 
discharged from the study.  
 
If, following study medication administration, it is determined that the subject may have been or 
was pregnant at the time of study medication exposure (including at least 2 days after study 
medication administration) the investigator must immediately notify the Medical Monitor and 
record the event on a pregnancy surveillance form. While not an AE or SAE, the investigator 
must report every pregnancy using a pregnancy surveillance form and follow the reporting 
procedures described for SAE reporting (Section 10.2.2). 
 
Protocol-required procedures for trial discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy (e.g., x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated. In addition, the investigator must report 
to the Medical Monitor on the pregnancy surveillance form, follow-up information regarding the 
course of the pregnancy, including perinatal and neonatal outcome. Infants should be followed 
for a minimum of six weeks. 
  


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Date:  04 MAY 2017                                                                                                   
12. 
STATISTICAL CONSIDERATIONS 
12.1. 
Sample Size and Power Consideration 
Based on results from a previous study with similar design, the expected standard deviation for 
the primary efficacy parameter is approximately 23.7%. The mean difference between the two 
Active treatment groups is expected to be approximately 10 percentage points. With 
approximately 250 randomized subjects this study is expected to achieve approximately 85% 
power for the comparison between the two Active treatment groups, and more than 95% power 
for the pair-wise comparisons between each Active treatment group and the Vehicle group.  
Two-tail alpha will be set to 0.05 for all comparisons. 
12.2. 
Statistical Analysis of Efficacy  
The primary effectiveness analysis will consist of pair-wise comparison between each active 
treatment group and the vehicle treatment group, and between the two active treatment groups, 
based on the mean of per-subject percentages of target lesions judged to be clear on the PLA 
(PLA = 0) at Visit 8.  To conduct this analysis, the percentage of each subject’s target lesions 
judged to be clear on the PLA at Visit 8 will first be calculated for each subject.  Then the 
analysis will calculate the mean of this parameter for each treatment group (yielding an estimate 
of the mean percentage of clear lesions across subjects), and an analysis of variance (ANOVA) 
model will be used to perform all pair-wise comparisons among the treatment groups.  Pair-wise 
comparisons will be conducted on the least-squares means using the overall pooled error term of 
the model.  All efficacy analyses will be based on the per protocol (PP) population, defined as all 
randomized subjects who completed the study with no major protocol violation.  
 
A secondary effectiveness analysis will be conducted using the same methodology as the 
primary efficacy analysis based on the mean of per-subject percentages of target lesions judged 
to be clear or near-clear on the PLA (PLA <= 1) at Visit 8.  The primary and secondary analyses 
above will also be conducted separately for lesions in each body location, using the same 
methodology as specified above. 
 
In addition to the above Visit 8 analyses, each of these analyses will be conducted at each other 
visit where PLA scores are collected, as exploratory analyses. 
 
Three exploratory responder analyses will be conducted using the following criteria for 
classifying subjects as responders: 
 
Subjects with PLA = 0 for all 4 target lesions at Visit 8; 
Subjects with PLA = 0 for at least 3 target lesions at Visit 8; and 
Subjects with PLA <= 1 for all 4 target lesions at Visit 8. 
 
For each exploratory analysis, separate chi-square tests will be used to compare the percentage of 
responders between each active treatment group and the vehicle treatment group, and between 
the two active treatment groups.  The chi-square analyses may be supplemented by one logistic 
regression model for each exploratory analysis that will allow all 3 pairwise comparisons to be 
performed within a single model. 
 


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Date:  04 MAY 2017                                                                                                   
Duration of response will be calculated on a lesion basis by determining the percentage of clear 
lesions (PLA=0) at Visit 8 which remain clear at Visit 13.  This will be done for each treatment 
group separately. 
 
For all analyses, two-tail alpha will be set to 0.05 with no adjustment for multiple comparisons.  
ANOVAs will include Site in the model if doing so improves the sensitivity of the model for 
comparing treatment groups.   
 
12.3. 
Statistical Analysis of Safety Data 
Descriptive statistics will be calculated on the safety parameters using the ITT population. The 
proportion of subjects with treatment-emergent adverse events will be tabulated and presented by 
treatment and Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class. 
Vital signs, LSR scores and clinically relevant abnormal laboratory results will also be tabulated 
and presented by study medication. No inferential testing will be performed. 
 
Data from all randomized subjects will be presented and summarized. Safety summaries by study 
medication group will include listings by study medication of adverse events incidences within 
each MedDRA System Organ Class, and changes from pre-application values in vital signs. 
Adverse event summaries will be presented by study medication showing the proportion of 
subjects experiencing adverse events, both overall and by MedDRA System Organ Class. 
12.4. 
Interim Analysis 
An interim Analysis will not be conducted for this study.     
13. 
QUALITY CONTROL AND QUALITY ASSURANCE 
13.1. 
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 IEC/IRB, 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. 
 
13.2. 
Protocol Deviations, Violations and Exceptions 
A protocol deviation is non-adherence to protocol-specific study procedures or schedules that 
does not involve inclusion/exclusion criteria, primary objective variable criteria, and/or GCP 
 guidelines.  Deviations are considered minor and do not impact the study.  Deviations include 
study procedures that occurred outside the treatment windows (except for treatment application 
days).  
 
A protocol violation is defined as any divergence from the protocol-specific inclusion/exclusion 
criteria, subject is administered a prohibited medication, primary objective variable criteria, 
and/or GCP guidelines.  Protocol violations will be identified and recorded, by study center 
personnel, on the CRF. 
 


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Date:  04 MAY 2017                                                                                                   
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. 
13.3. 
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. 
 
13.4. 
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.   
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.  


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Date:  04 MAY 2017                                                                                                   
13.5. 
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 
13.6. 
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.  
13.7. 
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 
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. 


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Date:  04 MAY 2017                                                                                                   
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 
14. 
ETHICS AND GENERAL STUDY CONDUCT CONSIDERATIONS 
14.1. 
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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Date:  04 MAY 2017                                                                                                   
14.2. 
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. 
14.3. 
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. 
 
14.4. 
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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Date:  04 MAY 2017                                                                                                   
 
15. 
APPENDICES 
15.1. 
Subject Instruction Sheet 
A-101-SEBK-204 SUBJECT INSTRUCTION SHEET 
Please follow these instructions carefully. Contact the study staff at the telephone number noted 
below if you have any questions about the study: 
 
Contact: 
 
 
 
 
 
   Telephone:                                      
 
 
DURING THE STUDY: 
• Continue your routine cleansing regimen except avoid vigorous scrubbing of the Target 
Lesions (e.g., loofah, back brushes, scrubbing straps, abrasive washcloths, sponges and 
cleansing pads, etc.) 
• Continue your routine cosmetics and skin care products 
• Avoid exposing your Target Lesions to excessive natural or artificial ultraviolet radiation 
(e.g., sunlight, tanning beds) and use sunscreen on the Target Lesion, if excessive 
exposure cannot be avoided 
• The use of the following therapies to treat any of the Target Lesions are prohibited 
o Retinoids (oral or topical) 
o Corticosteriods (oral or topical) 
o Antimetabolites 
o LASER, light or other energy based therapy 
o Liquid nitrogen, electrodesiccation, curettage, imiquimod, ingenol mebutate 
o Microdermabrasion or superficial chemical peels 
o Antibiotics (oral or topical) 
• Use of self-tanner lotions/sprays are prohibited during the study. 
• Bring this subject instruction sheet with you to each visit. 
 
 
ON STUDY VISIT DAYS: 
• When appropriate for the Target Lesion location wear loose fitting clothing to the visit 
(Note: clothing that comes in contact with the study medication may be bleached) 
• Starting prior to Visit 2, do not apply any topical products to the Target Lesions, except 
for routine cleansing products, within 12 hours prior to the visit 
• After any study visit where a study medication treatment was performed do not: 
o Wash/submerge the Target Lesions for at least 6 hours 
o Apply any topical products to the Target Lesions for at least 6 hours. 
 
STUDY VISIT SCHEDULE: 
VISIT 2: 
Date:                            Time: 
VISIT 3: 
Date:                            Time: 


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Date:  04 MAY 2017                                                                                                   
VISIT 4: 
Date:                            Time: 
VISIT 5: 
Date:                            Time: 
VISIT 6: 
Date:                            Time: 
VISIT 7: 
Date:                            Time: 
VISIT 8: 
Date:                            Time: 
Thank you for following these instructions 


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Date:  04 MAY 2017                                                                                                   
15.2. 
Physician Lesion Assessment Scale-Training Manual (12JAN2016) 
 


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Date:  04 MAY 2017                                                                                                   


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Date:  04 MAY 2017                                                                                                   


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Date:  04 MAY 2017                                                                                                   


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Date:  04 MAY 2017                                                                                                   


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Date:  04 MAY 2017                                                                                                   


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Date:  04 MAY 2017                                                                                                   


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Date:  04 MAY 2017                                                                                                   


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Date:  04 MAY 2017                                                                                                   


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Date:  04 MAY 2017                                                                                                   


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Date:  04 MAY 2017                                                                                                   
 
16. 
References 
  
Chan HP, Maibach HI,. 2008. "Hydrogen Peroxide, Blanching, and Skin: an Overview." 
Cutaneous and Ocular Toxicology 307-309. 
Fitzpatrick, T. 1988. "The Validity and Practicality of Sun Reactive Skin Types I through VI." 
Arch Dermatology 869-871. 
Haffner C, Vogt T. 2008. "Seborrheic keratosis." JDDG: Journal der Deutschen 
Dermatologischen Gesellschaft 6(8):664-677. 
McKee PH, Calonje E, Granter S. 2005. "Seborrheic Keratosis." In Pathology of the Skin with 
Clinical Corrections, by Calonje E, Granter S McKee PH, Vol 2: 1158-1163. 
Philadelphia: Mosby. 
Motley. 2002. "Seborrheic Keratosis." In Treatment of Skin Disease Comprehensive Therapeutic 
Strategies, by Heymann W, Berth-Jones J, Coulson I Lebwohl M, 585-586. New York: 
Mosby. 
Pierson DBC, Bandel C, Ehrig T, Cockerell C. 2003. "Benign Epidermal Tumors and 
Proliferations." In Dermatology, by J, Jorizzo J, Rapini, R Bolognia, Vol 2 1 ed. 1697-
1703. NY: Mosby. 
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. 
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. 
Richardson. 1866. "On the Introduction of Peroxide of Hydrogen as a Medicine." The Lancet 
87 (2220):300. 
Schumb WC, Satterfield CN, and Wentworth RL. 1955. Hydrogen Peroxide. New York: 
Reinhold Publishing Comp. 
Watt BE, Proudfoot AT, Vale JA. 2004 . "Hydrogen Peroxide Poisoning (Review)." 
Toxicological Reviews 51-57. 
Zonios. 2007. "Probing Skin Interactionwith Hydrogen Peroxide Using Diffuse Reflectance 
Spectroscopy." Physicis in Medicine and Biology 269-278.