Clinical trial NCT03487588
Conditions: Seborrheic Keratosis
Sponsor: Aclaris Therapeutics, Inc.
Start date: 2018-03-21; Completion date: 2018-11-14
Enrollment: 41 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study is an open-label study designed to evaluate subject's satisfaction after treatment of seborrheic keratoses with A-101 40%.

Detailed description:

Arms: arm 1: Open Label Arm
Interventions: intervention 1: A-101 Topical Solution
Intervention descriptions: intervention 1: A-101 Topical Solution applied Day 1, Day 15 and Day 29

Protocol documents:
Prot_000.pdf: 
Protocol A-101-SEBK-402 
Version 3:  18 JUN 2018 
1 
A-101 (HYDROGEN PEROXIDE) TOPICAL SOLUTION,
40% (W/W) 
AN OPEN-LABEL STUDY ASSESSING SUBJECT 
SATISFACTION WITH A-101 HYDROGEN PEROXIDE 
TOPICAL SOLUTION, 40% (W/W) TREATMENT FOR 
SEBORRHEIC KERATOSES OF THE FACE, NECK, 
AND DECOLLETAGE (SK-FAN) 
Version 3.0 
18 JUNE 2018 




Protocol A-101-SEBK-402 
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INVESTIGATOR’S AGREEMENT 
 
I have received and read the Investigator’s Brochure for A-101.  I have read the A-101-SEBK-
402 protocol and agree to conduct the study as outlined.  I agree to maintain the confidentiality 
of all information received or developed in connection with this protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date 


Protocol A-101-SEBK-402 
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PROCEDURES IN CASE OF EMERGENCY 
 
Table 1: 
Emergency Contact Information 
Role in Study 
Name 
Address and Telephone Number 
Senior Director, Clinical 
Operations 
Judy Schnyder 
640 Lee Road 
Suite 200 
Wayne, PA 19087 
484-329-2144 
jschnyder@aclaristx.com 
Medical Monitor 
Esther Estes, MD, MPH 
640 Lee Road 
Suite 200 
Wayne, PA 19087 
484-321-2142 
eestes@aclaristx.com 
Serious Adverse Event (SAE) 
contact 
Kenneth Kostenbader, MD 
640 Lee Road 
Suite 200 
Wayne, PA 19087 
484-848-7012 
kkostenbader@aclaristx.com 
SAE Fax: 484-324-2359 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Amendment History:   
This is the second amendment to the original protocol dated 13-Feb-2018. 
Amendment Rationale: 
The rationale for Amendment 2 dated 18-Jun-2018 is to increase the enrollment age to 75 years 
old.   
Protocol 
Version 
Date 
Page/Section 
Revision 
1.0 
13-Feb-2018 
NA 
NA 
2.0 
16-Apr-2018 
1/Title Page 
Updated version number and date 
2.0 
16-Apr-2018 
2/Protocol Signature Page  
Updated version number and date 
2.0 
16-Apr-2018 
5-7/Amendment History and 
Rationale 
Listed all changes to the current version 
of the protocol 
2.0 
16-Apr-2018 
8/Methodology 
Changed “Each SK must be treated by the 
Principal Investigator or physician Sub-
Investigator” to “Each SK must be treated 
by a study trained healthcare provider at 
the site” 
2.0 
16-Apr-2018 
9/Inclusion Criteria 
#4d. and 5c. Changed “Be a discrete 
lesion and the only SK present when 
centered in the area outlined by the 
provided circular template” to “Be a 
discrete lesion (no overlapping lesions)” 
2.0 
16-Apr-2018 
9/Inclusion Criteria 
#6 Changed “Subjects must have had 
cryosurgery for SK removal within the 
last 3 months and prior to first treatment 
with A-101 (Hydrogen Peroxide) Topical 
Solution, 40% (w/w).” to “Subjects must 
have had cryosurgery for SK removal 
within the last 6 months and prior to first 
treatment with A-101 (Hydrogen 
Peroxide) Topical Solution, 40% (w/w).” 
2.0 
16-Apr-2018 
11/ Reference therapy, 
dosage and mode of 
administration 
Changed “Each SK must be treated by the 
Principal Investigator or physician Sub-
Investigator” to “Each SK must be treated 


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Protocol 
Version 
Date 
Page/Section 
Revision 
by a study trained healthcare provider at 
the site” 
2.0 
16-Apr-2018 
25/Overall Study Design 
Changed “Each SK must be treated by the 
Principal Investigator or physician Sub-
Investigator” to “Each SK must be treated 
by a study trained healthcare provider at 
the site” 
2.0 
16-Apr-2018 
28/Footnote 5 
Updated typo “Refer to Section 9.4” to 
“Refer to Section 8.4” 
2.0 
16-Apr-2018 
28/Footnote 12 
Changed “A-101 40% will be applied to 
each target and non-target SK by the 
Principal Investigator or physician Sub-
Investigator” to “A-101 40% will be 
applied to each target and non-target SK 
by a study trained healthcare provider at 
the site.”   
2.0 
16-Apr-2018 
29/Inclusion Criteria 
#4d. and 5c. Changed “Be a discrete 
lesion and the only SK present when 
centered in the area outlined by the 
provided circular template” to “Be a 
discrete lesion (no overlapping lesions)” 
2.0 
16-Apr-2018 
29/Inclusion Criteria 
#6 Changed “Subjects must have had 
cryosurgery for SK removal within the 
last 3 months and prior to first treatment 
with A-101 (Hydrogen Peroxide) Topical 
Solution, 40% (w/w).” to “Subjects must 
have had cryosurgery for SK removal 
within the last 6 months and prior to first 
treatment with A-101 (Hydrogen 
Peroxide) Topical Solution, 40% (w/w).” 
2.0 
16-Apr-2018 
31/Withdrawal Procedures 
Updated typo “Visit 10” to “Visit 11” 
2.0 
16-Apr-2018 
33/Concomitant 
Medications 
Removed typo “Subjects should refrain 
from changing the use of any concomitant 
therapies during the study.” 


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Protocol 
Version 
Date 
Page/Section 
Revision 
2.0 
16-Apr-2018 
33/Prohibited Therapies 
Updated typo “Starting with Visit 1” to 
“Starting with Visit 2” 
2.0 
16-Apr-2018 
33/Study Medication 
Treatment 
Changed “each target and non-target SK 
must be treated by the Principal 
Investigator or physician Sub-
Investigator” to “each target and non-
target SK must be treated by a study 
trained healthcare provider at the site.” 
2.0 
16-Apr-2018 
40/Target SK Identification 
Changed “Be a discrete lesion and the 
only SK present when centered in the area 
outlined by the provided circular 
template” to “Be a discrete lesion (no 
overlapping lesions)” 
2.0 
16-Apr-2018 
41/Target SK Identification 
Changed “Be a discrete lesion and the 
only SK present when centered in the area 
outlined by the provided circular 
template” to “Be a discrete lesion (no 
overlapping lesions)” 
2.0 
16-Apr-2018 
45/Vital Signs 
Updated typo “Section 12.4” to “Section 
11.6” 
2.0 
16-Apr-2018 
54/Written Informed 
Consent 
Removed typo “urine pregnancy test” 
2.0 
16-Apr-2018 
75 & 76/Appendix 3 
Added revised “End of Study Subject 
Satisfaction Assessment” 
3.0 
18-Jun-2018 
1/Title Page 
Updated version number and date 
3.0 
18-Jun-2018 
2/Protocol Signature Page  
Updated version number and date.  
Changed Sponsor Signature from Stuart 
Shanler, MD to David Gordon, MB, ChB. 
3.0 
18-Jun-2018 
5-7/Amendment History and 
Rationale 
Listed all changes to the current version 
of the protocol. 
3.0 
18-Jun-2018 
9 & 29/Inclusion Criteria 
Changed “Male or female between the 
ages of 30 and 65 years old.” to “Male or 
female between the ages of 30 and 75 
years old.” 


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1. 
SYNOPSIS 
Name of Sponsor/Company:  
Aclaris Therapeutics, Inc. 
640 Lee Road 
Suite 200 
Wayne, PA 19087 
Name of Investigational Product: 
A-101 (Hydrogen Peroxide) Topical Solution, 40% (w/w) 
Name of Active Ingredient: 
Hydrogen Peroxide 40% 
Title of Study:  
(SK-FAN) An Open-Label Study Assessing Subject Satisfaction with A-101 (Hydrogen 
Peroxide) Topical Solution, 40% (w/w) Treatment for Seborrheic Keratoses of the Face, 
Neck, and Décolletage. 
Study center(s):  Up to 3 Investigational Sites 
Studied period (months): 3 
Estimated date first subject enrolled:  March 5, 2018 
Estimated date last subject completed: September 5, 
2018 
Phase of development: IV 
 
Objectives: The main objective of this study is to assess subject satisfaction after treatment 
with A-101 40% on SKs of the face, neck, and décolletage. 
Methodology:  
Subjects will be naive to A-101 (Hydrogen Peroxide) Topical Solution, 40% (w/w) 
treatment.  Dermatologists will identify 3 eligible target SKs on each subject; 2 target SKs 
must be on the face, and the additional 1 target SK must be on the neck or décolletage.  Up to 
4 additional non-target SKs may be identified on the face, neck or décolletage.  Each SK 
must be treated by a study trained healthcare provider at the site.  Each target and non-target 
SK will be treated during up to 3 separate treatment visits: Visit 2, Visit 5 and Visit 7.  Each 
treatment visit requires up to 4 applications of A-101 (Hydrogen Peroxide) Topical Solution, 
40% (w/w) to each eligible target and non-target SK.  Each application will last up to 20 
seconds with about 60 seconds between applications. 
 
A total of 30 subjects will be enrolled.  Subjects will be interviewed by the study staff prior 
to study medication application to assess their dermatological medical history.  A trained 
photographer will document each subject’s SKs at every visit, and during Visit 2, subjects 
will have photographs taken of each SK at specified post treatment timepoints.   
Subjects will be assessed for adverse events related to study medication throughout the 
conduct of the study. 
 


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Number of subjects (planned): 30 subjects will be enrolled to the study 
Diagnosis and main criteria for inclusion:  
Inclusion Criteria: 
Subjects must meet all the following criteria to be considered for participation in this study: 
1. Subject can comprehend and is willing to sign an informed consent for participation 
in this study. 
2. Male or female between the ages of 30 and 75 years old. 
3. Subject has a clinical diagnosis of stable clinically typical Seborrheic Keratosis. 
4. Subject has 3 eligible Seborrheic Keratoses; 2 target SKs must be on the face, and 
the additional 1 target SK must be on the neck or décolletage.  Each target SK must 
meet the following requirements: 
a. Have a clinically typical appearance 
b. Have a Physician's Lesion Assessment of ≥ 2  
c. Have a diameter between 5 to 15 mm  
d. Be a discrete lesion (no overlapping lesions) 
e. Not be covered with hair which, in the investigator’s opinion, would interfere 
with the study medication treatment or the study evaluations 
f. Not be in an intertriginous fold 
g. Not be on the eyelids 
h. Not be within 5mm of the orbital rim 
i. Not be pedunculated 
5. Subject may have up to 4 additional non-target Seborrheic Keratoses on the face, 
neck or décolletage treated.  Each non-target SK must meet the following 
requirements:  
a. Have a clinically typical appearance 
b. Have a Physician's Lesion Assessment of ≥ 2  
c. Be a discrete lesion (no overlapping lesions) 
d. Not be covered with hair which, in the investigator’s opinion, would interfere 
with the study medication treatment or the study evaluations 
e. Not be in an intertriginous fold 
f. Not be on the eyelids 
g. Not be within 5mm of the orbital rim 
h. Not be pedunculated 
6. Subjects must have had cryosurgery for SK removal within the last 6 months and 
prior to first treatment with A-101 (Hydrogen Peroxide) Topical Solution, 40% 
(w/w).   
7. Target and non-target SKs must not have been previously treated. 
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 


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target or non-target SK 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 Keratoses. 
2. Subject has presence of multiple eruptive Seborrheic Keratoses (Sign of Lesser -
Trelat). 
3. Subject has current systemic malignancy. 
4. Subject has previously received A-101 (hydrogen peroxide) Topical Solution, 40% 
treatment. 
5. Subject has used any of the following therapies within the specified period prior to 
Visit 2 on, or in a proximity to any target or non-target SK, that in the investigator’s 
opinion interferes with the study medication treatment or the study assessments: 
a. LASER, light or other energy-based therapy (e.g., intense pulsed light [IPL], 
photo-dynamic therapy [PDT]; 30 days 
b. Imiquimod, 5-fluorouracil (5FU), or ingenol mebutate; 60 days 
c. Retinoids; 28 days 
d. Microdermabrasion or superficial chemical peels; 14 days 
6. Subject would require the use of any topical treatment (e.g., moisturizers, 
sunscreens) to any of the target or non-target SKs 12 hours prior to any study visit. 
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 or non-target SK that, in the 
investigator’s opinion, interferes with the study medication treatment or the study 
assessments: 
a. Cutaneous malignancy; 180 days 
b. Sunburn; currently 
c. Pre-malignancy (e.g., actinic keratosis); currently 
d. Body art (e.g., tattoos, piercing, etc.); currently 
e. Excessive tan; use of self-tanning lotions/sprays is 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 within 30 days prior to Visit 1. 


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Investigational product, dosage and mode of administration:  
A-101 (hydrogen peroxide) Topical Solution, 40% (w/w); hereafter referred to as A-101, will 
be supplied as a single-use applicator to be applied topically to Seborrheic Keratoses. 
The study drug, A-101 40%, is a clear, colorless solution that must be stored at room 
temperature (20-25º C or 68 -77 º F). 
Duration of treatment:  
The duration of the study participation is anticipated to be a maximum of 134 days per 
subject.  The final visit, (Visit 11), has a maximum allowable visit window of 7 days. 
Study visits are: 
• Visit 1 (Day -13 - 0) Screening 
• Visit 2 (Day 1) Study Medication Treatment 
• Visit 3 (Day 2) Follow-up Visit 
• Visit 4 (Day 8) Follow-up Visit 
• Visit 5 (Day 15) Study Medication Treatment (if PLA ≥ 1)  
• Visit 6 (Day 22) Follow-up Visit 
• Visit 7 (Day 29) Study Medication Treatment (if PLA ≥ 1) 
• Visit 8 (Day 36) Follow-up Visit  
• Visit 9 (Day 57) Follow-up Visit 
• Visit 10 (Day 85) Follow-up Visit 
• Visit 11 (Day 113) Follow-up Visit; End of Study  
Reference therapy, dosage and mode of administration: 
Study drug medication will be applied to 3 target SKs and up to 4 non-target SKs during 
Visit 2, and for SKs that meet the criteria for retreatment, again on Day 15 (Visit 5) and Day 
29 (Visit 7). 
Each SK must be treated by a study trained healthcare provider at the site.   
Study medication must be applied to each target and non-target SK for approximately 20 
seconds.  Each target and non-target SK may be treated up to 4 times with approximately 60 
seconds between each application. 
 


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Criteria for evaluation: 
Primary: 
• Subject satisfaction after treatment with A-101 (Hydrogen Peroxide) topical solution, 
40% (w/w) at Day 85 and Day 113. 
Secondary: 
• Effectiveness of treatment as measured by the PLA at Day 85 and Day 113. 
• Comparison of the PLA score(s) to treatment satisfaction at Day 85 and Day 113. 
 
Statistical methods: 
Efficacy Analysis: 
Descriptive statistics will be used to summarize the data.  Descriptive statistics will be used 
to summarize the effectiveness for this study.  The focus of the analyses will be the 
evaluation of the relationship between lesion outcomes and subject satisfaction scores from 
each of the subject satisfaction scales.  Because satisfaction is assessed on a subject level and 
not for each individual lesion, it will be necessary to first summarize multiple lesion 
outcomes into one score for each subject visit.  The analyses will then be implemented at 
each applicable visit by calculating separate Pearson correlations coefficients between (1) 
mean change from baseline in per-subject averaged PLA scores across all lesions, and (2) 
each subject satisfaction scale score at the visit.  As a sensitivity analysis, the above statistics 
will also be calculated using Spearman’s rank-order correlation.  Exploratory analyses 
similar to the above will also be conducted between (1) per-subject averaged percent of 
treated lesions clear (PLA = 0) and (2) each subject satisfaction scale score.  A similar 
exploratory analysis will also be conducted using per-subject averaged percent of lesions 
clear or near-clear (PLA < 2).  Additional multiple regression models may be used across 
groups of subject satisfaction scales, depending on the pattern of individual subject 
satisfaction scale outcomes. 
 
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, and discontinuation of 
subjects from study due to AEs.  Safety endpoints for AEs will be specified in the statistical 
analysis plan (SAP).  All safety endpoints will be summarized using descriptive statistics. 
 
 


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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
1. 
SYNOPSIS ...................................................................................................................8 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............13 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................18 
4. 
INTRODUCTION ......................................................................................................20 
5. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................24 
5.1. 
Objective .....................................................................................................................24 
6. 
INVESTIGATIONAL PLAN .....................................................................................25 
6.1. 
Overall Study Design ..................................................................................................25 
6.2. 
Number of Subjects ....................................................................................................26 
6.3. 
Treatment Assignment ................................................................................................26 
6.4. 
Dose Adjustment Criteria ...........................................................................................26 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................29 
7.1. 
Subject Inclusion Criteria ...........................................................................................29 
7.2. 
Subject Exclusion Criteria ..........................................................................................30 
7.3. 
Subject Withdrawal Criteria .......................................................................................30 
7.4. 
Withdrawal Procedures ...............................................................................................31 
7.5. 
Subject Replacement ..................................................................................................31 
7.6. 
Subject Identifier (SI) .................................................................................................31 
8. 
TREATMENT OF SUBJECTS ..................................................................................32 
8.1. 
Description of Study Drug ..........................................................................................32 
8.2. 
Previous Therapies ......................................................................................................32 
8.3. 
Concomitant Medications ...........................................................................................32 
8.4. 
Prohibited Therapies ...................................................................................................33 
8.5. 
Study Medication Treatment ......................................................................................33 
8.5.1. 
Preparing the Study Medication for Application ........................................................34 
8.5.2. 
Applying A-101 40% to the Face, Neck or Décolletage ............................................35 
8.6. 
Randomization and Blinding ......................................................................................37 
8.6.1. 
Randomization ............................................................................................................37 
8.6.2. 
Blinding ......................................................................................................................37 


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9. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................38 
9.1. 
Study Drug ..................................................................................................................38 
9.2. 
Study Drug Packaging and Labeling ..........................................................................38 
9.3. 
Study Drug Storage .....................................................................................................38 
9.4. 
Study Drug Preparation ..............................................................................................38 
9.5. 
Administration ............................................................................................................38 
9.6. 
Study Drug Accountability .........................................................................................38 
9.7. 
Study Drug Handling and Disposal ............................................................................39 
10. 
ASSESSMENT OF EFFICACY ................................................................................40 
10.1. 
Target SK Identification .............................................................................................40 
10.1.1. 
Standardized Photography ..........................................................................................42 
10.1.2. 
Physician’s Lesion Assessment (PLA) .......................................................................42 
10.1.3. 
SK Dimensions ...........................................................................................................43 
10.2. 
Subject Instructions ....................................................................................................43 
10.3. 
Subject Satisfaction Assessment.................................................................................44 
10.4. 
Study Supplies ............................................................................................................44 
11. 
ASSESSMENT OF SAFETY .....................................................................................45 
11.1. 
Vital Signs ..................................................................................................................45 
11.2. 
Other Evaluations .......................................................................................................45 
11.2.1. 
Demographic/Medical History ...................................................................................45 
11.3. 
Adverse and Serious Adverse Events .........................................................................46 
11.3.1. 
Definition of Adverse Events .....................................................................................46 
11.3.2. 
Serious Adverse Event (SAE) ....................................................................................46 
11.4. 
Relationship to Study Drug ........................................................................................47 
11.5. 
Severity .......................................................................................................................47 
11.6. 
Reporting Adverse Events ..........................................................................................48 
11.7. 
Withdrawal Due to an Adverse Event ........................................................................49 
12. 
STATISTICS ..............................................................................................................50 
13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................51 
13.1. 
Study Monitoring ........................................................................................................51 
13.2. 
Audits and Inspections ................................................................................................51 
13.3. 
Institutional Review Board (IRB) ...............................................................................51 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................53 


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14.1. 
Protocol Amendments ................................................................................................53 
14.2. 
Protocol Deviations, Violations, and Exceptions .......................................................53 
14.3. 
Training .......................................................................................................................53 
15. 
ETHICS ......................................................................................................................54 
15.1. 
Ethical Conduct of the Study ......................................................................................54 
15.2. 
Written Informed Consent ..........................................................................................54 
16. 
DATA HANDLING AND RECORDKEEPING .......................................................55 
16.1. 
Inspection of Records .................................................................................................55 
16.2. 
Data Management .......................................................................................................55 
16.3. 
Regulatory Documents ...............................................................................................55 
16.4. 
Contractual Requirements ..........................................................................................55 
16.5. 
Retention of Records ..................................................................................................55 
17. 
LIST OF REFERENCES ............................................................................................57 
18. 
APPENDICES ............................................................................................................58 
APPENDIX 1. ................................................................................................................................59 
APPENDIX 2. ................................................................................................................................61 
APPENDIX 3. ................................................................................................................................72 
 


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LIST OF TABLES 
Table 1: 
Emergency Contact Information ...................................................................................4 
Table 2: 
Abbreviations and Specialist Terms ...........................................................................18 
Table 3: 
Study Design and Schedule of Assessments ..............................................................27 
Table 4: 
Investigational Product ...............................................................................................32 
Table 5: 
Physician’s Lesion Assessment Definitions ...............................................................43 
Table 6: 
Fitzpatrick Skin Type Scoring System .......................................................................45 
 


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LIST OF FIGURES 
Figure 1: 
Diagram Showing the Process for Preparing and Applying A-101 40% ...................35 
Figure 2: 
Target and Non-Target SK Identification ...................................................................41 
 
  


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
The following abbreviations and specialist terms are used in this study protocol. 
Table 2: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
A-101 40% 
A-101 Hydrogen Peroxide Topical Solution, 40% 
(w/w) 
AE 
Adverse event 
ANCOVA 
Analysis of Covariance 
ºC 
Degrees Centigrade 
CMH 
Cochran-Mantel-Haenszel 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
e.g. 
For example, (Latin; exempla gratia) 
EC 
Ethics Committee 
ºF 
Degrees Fahrenheit 
FDA 
Food and Drug Administration 
5FU 
5 Fluorouracil 
G 
Gram 
GCP 
Good Clinical Practice 
HCP 
Healthcare Provider 
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 


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Abbreviation or Specialist Term 
Explanation 
ITT 
Intent to Treat 
LOCF 
Last Observed Carried Forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
Milliliter 
Mm 
Millimeter 
NB 
Note Bene 
NCS 
Not Clinically Significant 
OTC 
Over the Counter 
PDT 
Photodynamic Therapy 
PI 
Principal Investigator 
PLA 
Physician’s Lesion Assessment 
PP 
Per Protocol 
SAE 
Serious Adverse Event 
SDV 
Source Data Verification 
SI 
Subject Identifier 
SK 
Seborrheic Keratosis 
SOP 
Standard Operating Procedure 
TEAE 
Treatment Emergent Adverse Events 
US 
United States 
WOCBP 
Woman of Childbearing Potential 


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4. 
INTRODUCTION 
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). 
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 


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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. 
 
Summary of Previous Clinical Trials with A-101 Solution in Seborrheic Keratosis 
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% Solution or matching vehicle. 
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 (supported by the sensitivity analyses) as well as the 
secondary and exploratory analyses. 
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 


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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 7 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. 
 
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 up 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 (supported by the sensitivity analyses) as well as the 
secondary and exploratory analyses. 
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. 


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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. 
A-101-SEBK-303 
A-101-SEBK-303 was a large 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. 
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. 


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5. 
TRIAL OBJECTIVES AND PURPOSE 
The rationale of this study is to understand a subject’s experience and satisfaction after treatment 
with A-101 40% and how that correlates with a healthcare provider’s assessment based on PLA 
score. 
Aclaris Therapeutics, Inc. recently completed three phase III clinical studies (301, 302, and 303) 
that demonstrated the safety and efficacy of A-101 40% in treating Seborrheic Keratoses. 
5.1. 
Objective 
The objective of this study is to assess subject satisfaction after treatment with A-101 40% on 
SKs of the face, neck, and décolletage. 
 


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6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
This study is an open-label study designed to evaluate subject’s satisfaction after treatment of 
seborrheic keratoses with A-101 40%.   The subject’s treatment application will be documented 
via a series of photographs to aid in the assessment of the treated SK and to mimic real-world 
treatment environment.  
Dermatologists (investigators) will identify 3 eligible target SKs on each subject; 2 target SKs 
must be on the face, and the additional 1 target SK must be on the neck or décolletage.  Up to 4 
additional non-target SKs may be identified on the face, neck or décolletage.  Each target and 
non-target SK will be treated during up to 3 separate treatment visits: Visit 2, Visit 5, and Visit 7.  
Each SK must be treated by a study trained healthcare provider at the site.  Retreatment of 
identified target and non-target SKs will be determined by the physician using the Physicians 
Lesion Assessment Scale (PLA).  Target and non-target SKs that have been assigned a PLA of ≥ 
1 will be treated on Day 15 and Day 29.  Each treatment visit requires up to 4 applications of A-
101 (Hydrogen Peroxide) Topical Solution, 40% (w/w) to each eligible target and non-target SK.  
Each application will last up to 20 seconds with about 60 seconds between applications. 
A total of 30 subjects will be enrolled.  A trained photographer will document each subject’s 
target and non-target SKs at every visit. During Visit 2, subjects will have photographs taken of 
each SK at specified post treatment timepoints.   
Subjects will be assessed for adverse events related to A-101 40% throughout the conduct of the 
study. 
Subjects will be required to complete a total of 11 study visits.  The protocol defined study visits 
are: 
• Visit 1 (Day -13 - 0) Screening 
• Visit 2 (Day 1) Study Medication Treatment 
• Visit 3 (Day 2) Follow-up Visit 
• Day 4 (Day 8) Follow-up Visit 
• Visit 5 (Day 15) Study Medication Treatment (if PLA ≥ 1) 
• Visit 6 (Day 22) Follow-up Visit 
• Visit 7 (Day 29) Study Medication Treatment (if PLA ≥ 1) 
• Visit 8 (Day 36) Follow-up Visit 
• Visit 9 (Day 57) Follow-up Visit 
• Visit 10 (Day 85) Follow-up Visit 
• Visit 11 (Day 113) Follow-up Visit; End of Study 
 


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Refer to Table 3: Study Design and Schedule of Assessments for a complete list of protocol 
required study assessments. 
6.2. 
Number of Subjects 
A total of 30 subjects will be treated on the study at 3 investigational sites in the US. 
6.3. 
Treatment Assignment 
This is an open-label study. 
6.4. 
Dose Adjustment Criteria 
If a subject refuses the initial treatment or retreatment, the investigator must report the visit 
number, visit date, target SK number(s) that 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 SKs 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 5 or Visit 7.


Protocol A-101-SEBK-402 
 
 
 
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Table 3: 
Study Design and Schedule of Assessments 
Visit 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
Treatment Day 
Day -13 - 0 
Day 1 
Day 2 
Day 8 
Day 15 
Day 22 
Day 29 
Day 36 
Day 57 
Day 85 
Day 113 
Visit Window 
N/A 
N/A 
N/A 
± 1 day 
± 1 day 
± 1 day 
± 1 day 
± 1 day 
± 7 days 
± 7 days 
± 7 days 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/ Exclusion1 
X 
X 
 
 
 
 
 
 
 
 
 
Subject Identifier2 
X 
 
 
 
 
 
 
 
 
 
 
Dermatological Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Fitzpatrick Skin Type Assessment3 
X 
 
 
 
 
 
 
 
 
 
 
Vital Signs4 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
Prior Medications/Therapies5 
X 
 
 
 
 
 
 
 
 
 
 
Target and Non-Target SK 
Identification6 
X 
 
 
 
 
 
 
 
 
 
 
Physician’s Lesion Assessment7 
X 
X 
X 
X 
X 
 
X 
 
 
X 
X 
SK Dimensions8 
X 
X 
X 
X 
X 
 
X 
 
 
X 
X 
SK Photography9 
X 
X10 
X11 
X 
X10 
X 
X10 
X 
X 
X 
X 
Study Medication Application12 
 
X 
 
 
X 
 
X 
 
 
 
 
Subject Satisfaction Assessment13 
 
X 
X 
 
 
X 
 
X 
 
X 
X 
Concomitant Therapies14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events15 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1Subject inclusion/exclusion criteria will be reassessed prior to enrollment during Visit 2. 


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2Investigational sites will assign a unique five-digit subject identifier to each subject at Visit 1, formatted as NN-NNN where the first 2 digits are the site number, and the final 3 digits are 
the subject number that must be assigned in ascending numerical order (using leading zeroes, as appropriate).  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 Table 6 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, Visit 5, Visit 7 
Visit 10, and Visit 11. 
5Prior medications/therapies will be collected for a time-period of 13 days prior to Visit 1.  Refer to Section 8.4 for a list of permitted and restricted concomitant medications. 
6The treating investigator will identify 3 target SKs and up to 4 non-target SKs.  Two (2) target SKs must be on the face, and the additional 1 target SK must be on the neck or décolletage.  
The 4 non-target SKs may be located on the face, neck, or décolletage. 
7The investigator will use the Physician’s Lesion Assessment (PLA) to assess the severity of each target and non-target SKs at Visits 1, 2, 3, 4, 5, 7, 10, and 11.  At Visit 2, Visit 5 and Visit 
7, the investigator must assess each target and non-target SK prior to application of the study medication.  In order to be eligible for enrollment to the study during Visit 2, the subject must 
have a PLA grade ≥ 2 for each target and non-target SK. 
8The investigator will measure the dimensions of each target and non-target SK at Visits 1, 2, 3, 4, 5, 7, 10 and 11.  At Visit 2, Visit 5 and Visit 7, the investigator must measure each target 
and non-target SK prior to application of the study medication.  In order to be eligible for enrollment to the study during Visits 1 and 2, each target SK must have a diameter that is between 
≥ 5 and ≤ 15 mm (inclusive) and be raised.  In order to be eligible for enrollment to the study during Visits 1 and 2, each non-target SK must be a raised SK.  At Visits 3, 4, 5, 7, and 10 the 
investigator must assess the thickness of each target and non-target SK above the surrounding skin.  Additional target and non-target SK requirements are outlined in Section 10.1 . 
9Each target and non-target SK will be photographed at all study visits using the Aclaris Therapeutics, Inc. supplied photography equipment. 
10During Visit 2 each target and non-target SK will be photographed prior to the application of A-101 40%, 10 minutes post application (+2 minutes), and 1-hour post application (± 10 
minutes).  During Visit 5 and Visit 7, the target and non-target SKs will be photographed prior to the application of A-101 40%, if applicable. 
11During Visit 3 each target and non-target SK will be photographed 24-hours post application during Visit 2 (± 2 hours). 
12 A-101 40% will be applied to each target and non-target SK by a study trained healthcare provider at the site.  Each target and non-target SK will be treated with A-101 40% following 
confirmation of subject eligibility and study enrollment at Visit 2.  If a target or non-target SK meets the criteria for retreatment as defined in Section 9.5, the SK will be retreated at Visit 5 
and Visit 7.  Following application of A-101 40%, subjects must NOT wash/submerge a target and non-target SK for at least 6 hours and they must NOT apply any topical products to any 
target or non-target SK for at least 6 hours. 
13Subjects will be asked to assess how satisfied they are with the treatment experience they received for the target and non-target SKs at the specified visits.  On Visit 2 the subject will 
complete the assessment prior to application of A-101 40%.  On Visit 3 the subjects will complete the assessment approximately 24 hours after the treatment.  On Visit 6 and Visit 8 the 
subjects will complete the assessment approximately 1 week after the treatment, only if the subject received treatment on Visit 5 or Visit 7. The subject will complete the assessment during 
the Visit 10 and Visit 11. 
14All concomitant therapies including (topical and oral) prescription medications, over the counter medications, 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 and non-target 
SKs within 12 hours prior to any study visit. 
15The reporting period for SAEs begins when the subject signs the informed consent form.  Refer to Section 11.6  for instructions on the reporting of SAEs.  Non-serious clinical adverse 
events will be collected following the application of the study medication at Visit 2 and continue through Visit 11.  All safety reporting (AEs and SAEs) will conclude at Visit 11. 


Protocol A-101-SEBK-402 
 
 
 
 
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7. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1. 
Subject Inclusion Criteria 
Subjects must meet all the following criteria to be considered for participation in this study: 
1. Subject can comprehend and is willing to sign an informed consent for participation in 
this study. 
2. Male or female between the ages of 30 and 75 years old. 
3. Subject has a clinical diagnosis of stable clinically typical Seborrheic Keratosis. 
4. Subject has 3 eligible Seborrheic Keratoses; 2 target SKs must be on the face, and the 
additional 1 target SK must be on the neck or décolletage.  Each target SK must meet the 
following requirements: 
a. Have a clinically typical appearance 
b. Have a Physician's Lesion Assessment of ≥ 2  
c. Have a diameter between 5 to 15 mm 
d. Be a discrete lesion (no overlapping lesions) 
e. Not be covered with hair which, in the investigator’s opinion, would interfere with 
the study medication treatment or the study evaluations 
f. Not be in an intertriginous fold 
g. Not be on the eyelids 
h. Not be within 5mm of the orbital rim 
i. Not be pedunculated 
5. Subject may have up to 4 additional non-target Seborrheic Keratoses on the face, neck or 
décolletage treated.  Each non-target SK must meet the following requirements: 
a. Have a clinically typical appearance 
b. Have a Physician's Lesion Assessment of ≥ 2 
c. Be a discrete lesion (no overlapping lesions) 
d. Not be covered with hair which, in the investigator’s opinion, would interfere with 
the study medication treatment or the study evaluations 
e. Not be in an intertriginous fold 
f. Not be on the eyelids 
g. Not be within 5mm of the orbital rim 
h. Not be pedunculated 
6. Subjects must have had cryosurgery for SK removal within the last 6 months and prior to 
first treatment with A-101 (Hydrogen Peroxide) Topical Solution, 40% (w/w). 
7. Target and non-target SKs must not have been previously treated. 
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 
or non-target SK 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. 


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7.2. 
Subject 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 Keratoses. 
2. Subject has presence of multiple eruptive Seborrheic Keratoses (Sign of Lesser -Trelat). 
3. Subject has current systemic malignancy. 
4.  Subjects have previously received A-101 (hydrogen peroxide) Topical Solution, 40% 
treatment. 
5. Subject has used any of the following therapies within the specified period prior to Visit 
2 on, or in a proximity to any target or non-target SK, that in the investigator’s opinion 
interferes with the study medication treatment or the study assessments: 
a. LASER, light or other energy-based therapy (e.g., intense pulsed light [IPL], photo-
dynamic therapy [PDT]; 30 days 
b. Imiquimod, 5-fluorouracil (5FU), or ingenol mebutate; 60 days 
c. Retinoids; 28 days 
d. Microdermabrasion or superficial chemical peels; 14 days 
6. Subject would require the use of any topical treatment (e.g., moisturizers, sunscreens) to 
any of the target or non-target SKs 12 hours prior to any study visit. 
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 or non-target SK that, in the investigator’s 
opinion, interferes with the study medication treatment or the study assessments: 
a. Cutaneous malignancy; 180 days 
b. Sunburn; currently 
c. Pre-malignancy (e.g., actinic keratosis); currently 
d. Body art (e.g., tattoos, piercing, etc.); currently 
e. Excessive tan; use of self-tanning lotions/sprays is 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 within 30 days prior to Visit 1. 
7.3. 
Subject Withdrawal Criteria 
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 criterion. 


Protocol A-101-SEBK-402 
 
 
 
 
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• Use of a prohibited medication during the treatment period. 
• 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. 
7.4. 
Withdrawal Procedures 
If a subject withdraws from the study prior to Visit 11, 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, 
monitoring of the subject will continue until the event has resolved or stabilized, until the subject 
is referred to the care of a local health care professional, or until a determination of a cause 
unrelated to the study drug or study procedure is made. 
7.5. 
Subject Replacement 
If a subject is enrolled to the study but does not receive a dose of study drug, then the subject 
may 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 enrolled using the same subject identifier and 
must sign a new informed consent form. 
7.6. 
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. 


Protocol A-101-SEBK-402 
 
 
 
 
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8. 
TREATMENT OF SUBJECTS 
8.1. 
Description of Study Drug 
Table 4: 
Investigational Product 
 
Investigational Product 
Product Name: 
A-101 (Hydrogen Peroxide) Topical Solution, 40% (w/w)  
A-101 Concentration (%): 
Hydrogen peroxide 40% (w/w) 
Pharmaceutical Form 
Solution 
Route of Administration 
Topical 
Manufacturer 
James Alexander Corporation, Blairstown NJ 
Storage Conditions 
Room temperature: 59ºF to 77ºF (15ºC to 25ºC) protected 
from excessive heat, open flame and combustibles, out of 
direct sunlight and in a well-ventilated, dry area.  Excursions 
from these conditions must be reported to Aclaris 
Therapeutics, Inc.    
Application 
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 and non-target SK for 
approximately 20 seconds, then allow each target and non-
target SK to remain undisturbed for approximately 60 
seconds.  Repeat the application/waiting cycle until the A-101 
40% has been applied to each target and non-target SK up to 
4 times.  Subjects may receive up to 3 treatments. (Visit 2, 
Visit 5 and Visit 7) 
Activated Applicators 
Activated applicators are stable for 4 hours at room 
temperature 59ºF to 77ºF (15ºC to 25ºC) 
8.2. 
Previous Therapies 
During Visit 1, the investigator or designee will question the subject to ensure they have not used 
any excluded therapies (Section 8.4). 
8.3. 
Concomitant Medications 
Concomitant therapies are any new or existing therapy received from Visit 1 until discharge from 
the study. 


Protocol A-101-SEBK-402 
 
 
 
 
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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.  
All new or modified concomitant therapies used during the study must be recorded in the subject 
CRF. 
8.4. 
Prohibited Therapies 
During the course of this study, subjects are prohibited from using the following treatment 
therapies to treat any of the target and non-target SKs: 
• Retinoids (topical) 
• Corticosteroids (topical) 
• 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 and non-target SK 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 or non-target SK for at least 6 hours and must not 
apply any topical products to the target or non-target SK for at least 6 hours. 
8.5. 
Study Medication Treatment 
A-101 40% is for external, topical use on the target or non-target SK on the appropriate study 
subject only. 
The Principal Investigator or physician Sub-Investigator performing the A-101 40% treatments 
must comply with the A-101 40% storage conditions outlined in Section 8.1.   
At Visit 2, and Visit 5 and Visit 7 if applicable, each target and non-target SK must be treated by 
a study trained healthcare provider at the site. 
At Visit 5 and Visit 7, all identified target and non-target SKs that have a PLA grade of ≥ 1 will 
be re-treated with A-101 40%.  If in the investigator’s opinion, the lesion is not appropriate for 
re-treatment (e.g. cutaneous AE) treatment will be withheld.  The reason for withholding 
treatment will documented in the comment section of the subject’s CRF and the AE CRF if 
appropriate.   


Protocol A-101-SEBK-402 
 
 
 
 
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8.5.1. 
Preparing the Study Medication for Application 
To perform a study medication treatment for a target or non-target SK a HCP at the site will 
select the appropriate A-101 40% applicator.  The following instructions outline the procedure 
for application of A-101 40% to the target or non-target SK: 
• Prepare for the treatment: 
• Wash your hands prior to, and after completing the A-101 40% treatments  
• Wear nitrile or vinyl examination gloves during the treatment; latex gloves are 
prohibited 
• Select the applicator  
• Visually inspect the applicator for damage: 
• If the applicator appears damaged do not use it for the treatment, contact 
the study monitor for return/disposal instructions and select an unused 
applicator for the treatment 
• If the applicator is intact, proceed with the treatment process as outlined in 
Figure 1 
 


Protocol A-101-SEBK-402 
 
 
 
 
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Figure 1: 
Diagram Showing the Process for Preparing and Applying A-101 40% 
 
1. Each target and non-target SK should be cleaned using an alcohol wipe prior to 
application of A-101 40%. 
2. Hold the A-101 40% applicator so that the applicator cap is pointing up. 
3. Crush the ampule in the applicator by applying pressure to the center of the barrel of the 
applicator. 
4. Remove the sleeve. 
5. Tap the barrel of the applicator to ensure the solution is free of the crushed ampule. 
6. Gently remove the cap by twisting while pulling away from the applicator. 
7. Express a single drop of A-101 40% so that the tip of the applicator becomes wet. 
8. Apply the solution to the target or non-target SK in a circular motion. 
8.5.2. 
Applying A-101 40% to the Face, Neck or Décolletage  
To apply A-101 40% to the target or non-target SK the HCP will follow these treatment 
instructions: 
• Do not apply A-101 40% to eyes, mouth, mucous membranes, open wounds 


Protocol A-101-SEBK-402 
 
 
 
 
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• Do not apply A-101 40% to the eyelids or within 5 mm of the orbital rim 
• If, in the investigator’s opinion it is needed to ensure no A-101 40% enters the 
eye: 
• 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. 
• Apply 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 
• 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 or non-target SK 
• 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 or non-target SK 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 target or non-target SK and then move applicator 
around in a circular motion to fully saturate the SK.  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 or non-target SK is wet with study medication at the end of the 
approximately 20 second application 
• Allow the target or non-target SK to remain undisturbed for approximately 60 
seconds 
• After approximately 60 seconds repeat the approximately 20 second application 
process 
Repeat the application/waiting cycle until the study medication has been applied to each target or 
non-target SK up to 4 times.  It is acceptable to treat the target and non-target SKs sequentially to 
minimize treatment time; such that, after treatment is applied to the 3rd SK, the 60 second wait 
time between applications would be met.  


Protocol A-101-SEBK-402 
 
 
 
 
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Record the time the final treatment is completed for the last treated target or non-target SK as the 
Treatment Completion Time. 
8.6. 
Randomization and Blinding 
8.6.1. 
Randomization 
This is an open-label study and therefore randomization is not applicable. 
8.6.2. 
Blinding 
This is an open-label study and therefore the clinical drug supplies are not blinded.   


Protocol A-101-SEBK-402 
 
 
 
 
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9. 
STUDY DRUG MATERIALS AND MANAGEMENT 
9.1. 
Study Drug 
The study medication is A-101 (Hydrogen Peroxide) Topical Solution, 40% (w/w).  The study 
medication is a clear, colorless solution. 
9.2. 
Study Drug Packaging and Labeling 
A-101 (Hydrogen Peroxide) Topical Solution, 40% (w/w) will be provided by Aclaris 
Therapeutics, Inc. and labeled 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. 
9.3. 
Study Drug Storage 
Investigational sites will be supplied with open-label stock of A-101 40%.  Investigational study 
medication supplies are only to be used for subjects properly consented and enrolled to this 
study. 
A-101 40% must be stored in a location where there is limited access to the investigational study 
medication at 59ºF to 77ºF (15ºC to 25ºC) excessive heat, open flame and combustibles, in a 
well-ventilated, dry area.  Excursions from these temperature ranges must be reported to Aclaris 
Therapeutics, Inc. 
9.4. 
Study Drug Preparation 
Activated applicators are stable for 4 hours at room temperature (59ºF to 77ºF or 15ºC to 25ºC). 
9.5. 
Administration 
The subject will receive up to 4 applications to each target or non-target SK at Visit 2, and if the 
subject meets retreatment criteria, at Visit 5 and Visit 7. 
Apply study medication to each target and non-target SK for approximately 20 seconds.  Allow 
each target and non-target SK to remain undisturbed for approximately 60 seconds.  Repeat the 
application/waiting cycle until the study medication has been applied to each target and non-
target SK up to 4 times.  Subjects may receive up to 3 treatments (Visit 2, Visit 5 and Visit 7). 
9.6. 
Study 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 


Protocol A-101-SEBK-402 
 
 
 
 
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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. 
9.7. 
Study Drug Handling and Disposal 
Nitrile or vinyl examination gloves must be worn during the application process.  Latex gloves 
are prohibited. 


Protocol A-101-SEBK-402 
 
 
 
 
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10. 
ASSESSMENT OF EFFICACY 
Similar lighting conditions and subject positioning should be used for all evaluations for a given 
subject. 
10.1. 
Target SK Identification 
At Visit 1, the investigator will identify up to 7 Seborrheic Keratoses on each subject for 
treatment and evaluation.  Three (3) target lesion must be identified, and up to 4 non-target 
lesions may be identified.  Two (2) target SKs must be on the face, and the additional 1 target SK 
must be on the neck, or décolletage.   Up to 4 additional non-target lesions may be on the face, 
neck, or décolletage.  
Face: 
• 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) 
• Horizontally from tragus to tragus, excluding the eyelids and areas within 
5mm of the orbital rim. 
Neck: 
• Vertically from the mandibular ridge vertically down to the top of the 
collar bone  
Décolletage:  
• From the collar bone down including the shoulders and cleavage area 
 
At Visit 1, each target SK must: 
• Have a clinically typical appearance 
• Have a PLA of ≥2 
• Have a diameter between 5 to 15 mm 
• Be a discrete lesion (no overlapping lesions) 
• 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. 
 
At Visit 1, each non-target SK must: 
• Have a clinically typical appearance 


Protocol A-101-SEBK-402 
 
 
 
 
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• Have a PLA of ≥2 
• Be a discrete lesion (no overlapping lesions) 
• 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. 
Record the approximate location of each target and non-target SK on the body chart in the CRFs. 
Number the target SK starting with 1 and proceeding up to 3 with no number omitted or reused.  
The target SKs on the face should be numbered 1 and 2, and the additional 1 SK on the neck 
and/or décolletage should be numbered 3.  The non-target SKs should be numbered 4-7 starting 
with 4 and proceeding up to 7 with no number omitted or reused. 
Aclaris Therapeutics, Inc. will provide the investigational site with standard circular templates 
and colored stickers that are to be used to identify the target and non-target SKs. 
At Visit 1, the investigator and a HCP will identify the target and non-target SKs by placing 2 
appropriately colored stickers approximately 180 degrees opposite each other with the target or 
non-target SK in the center of the area outlined by the provided circular template (Refer to 
Figure 2.  Figure not to scale): 
Figure 2: 
Target and Non-Target SK Identification 
 


Protocol A-101-SEBK-402 
 
 
 
 
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Write the target or non-target SK number on one of the identification (ID) stickers. The ID 
stickers must be visible in the study photographs.  The target and non-target SK #/ID sticker 
color relationships are: 
• Target SK on face#1/white ID stickers 
• Target SK on face #2/yellow ID stickers 
• Target SK on neck or décolletage #3/green ID stickers 
• Non-Target SK on the face, neck or décolletage #4/pink ID stickers 
• Non-Target SK on the face, neck or décolletage #5/grey ID stickers 
• Non-Target SK on the face, neck or décolletage #6/purple ID stickers 
• Non-Target SK on the face, neck or décolletage #7/orange ID stickers 
At each study visit a HCP from the investigational staff will confirm the location of each target 
and non-target SK using an appropriate combination of the Visit 2 hard-copy reference prints and 
the body charts. The staff member will identify the target and non-target SKs by placing 2 
appropriately colored ID stickers, with the target or non-target SK number written on one sticker, 
approximately 180 degrees opposite each other with the target or non-target SK in the center of 
area outlined by the provided circular template. 
10.1.1. 
Standardized Photography 
At each study visit a qualified investigational center staff member will take standardized color 
photographs of each target and non-target SK. 
The photographs are to document the location of the target and non-target SK and to assist with 
relocating the target and non-target SK and the target and non-target SK ID stickers must be 
visible in the photographs.  The subject’s identity will not be revealed in the study photographs.  
These photographs will also be used to document the treatment effects of A-101 40% over time. 
At Visit 2, the photographs must be taken prior to the study medication application, 10 minutes 
post application, and 1-hour post application of A-101 40%.  At Visit 5 and Visit 7, the 
photographs will be taken prior to study medication application, if applicable.  At Visit 3 
photographs must be taken 24 hours post application of A-101 40% on Visit 2. 
Care must be taken to ensure the same lighting, background, subject positioning relative to the 
camera and camera settings are used for each photograph. 
Sites will be provided with photography equipment and supplies necessary for obtaining the 
target and non-target SK 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. 
10.1.2. 
Physician’s Lesion Assessment (PLA) 
The PLA is the investigator’s assessment of the severity of the target and non-target SK at a 
particular time point.  The investigator may refer to other evaluations (e.g., prior photographs) to 
assist with these assessments. 


Protocol A-101-SEBK-402 
 
 
 
 
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At Visits 1, 2, 3, 4, 5, 7, 10, and 11 the investigator will assess the target and non-target SK using 
the scale below and report the one integer that best describes the severity of the target or non-
target SK.  At Visit 2 and if applicable at Visit 5 and Visit 7, the investigator must complete the 
PLA prior to the study medication treatment. 
Table 5: 
Physician’s Lesion Assessment Definitions 
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 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 enrollment to the study, each target and non-
target SK must have a PLA grade of ≥ 2. 
10.1.3. 
SK Dimensions 
At Visit 1 and Visit 2 prior to study enrollment, the investigator will measure the diameter and 
thickness of each target and non-target SK using the ruler provided. 
The investigator must measure the diameter of the longest axis of each target and non-target SK 
in millimeters (mm) as follows: 
• Diameter (i.e., the length of the longest axis)  
• Thickness (height above the surrounding skin) 
The PLA (the thickness) of the target and non-target SKs will be measured by the investigator at 
Visits 3, 4, 5, 7, 10, and 11.  When the visit coincides with treatment (Visits 2, 5 and 7), the 
thickness must be measured prior to the application of study medication. 
10.2. 
Subject Instructions 
An investigational center staff member will dispense a Subject Instruction Sheet to each subject 
at Visit 1 (Refer to Appendix 1). 
Throughout the study, the subjects should: 
• Continue their routine cleansing regimen  
• Continue their routine cosmetics and skin care products 
• Avoid exposing the target and non-target SKs to excessive natural or artificial ultraviolet 
radiation (e.g., sunlight, tanning beds) and use sunscreen on the target and non-target 
SKs, if excessive exposure cannot be avoided 


Protocol A-101-SEBK-402 
 
 
 
 
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• 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 and non-target SK locations, 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 or non-target SKs 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: 
• Wash/submerge the target or non-target SKs for at least 6 hours 
• Apply any topical products to the target or non-target SKs for at least 6 hours 
10.3. 
Subject Satisfaction Assessment 
Subjects will be asked to assess their level of satisfaction regarding the study medication 
treatment experience.  The subject survey will be completed at Visits 2, 3, 6 (only if treated at 
Visit 5), 8 (only if treated at Visit 7), 10, and 11. (See Appendix 3) 
10.4. 
Study Supplies 
Aclaris Therapeutics, Inc. will provide: 
• An appropriate ruler, or other instrument, for measuring the diameter and thickness of the 
target ad non-target SKs 
• Templates for use when identifying target and non-target SKs 
• Equipment, supplies and training for taking standardized photographs 


Protocol A-101-SEBK-402 
 
 
 
 
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11. 
ASSESSMENT OF SAFETY 
In addition to reporting adverse events throughout the study the investigator, a designated and 
appropriately trained HCP will perform the safety assessments according to the schedules noted 
below. 
11.1. 
Vital Signs 
Vital signs will be measured by a qualified staff member at Visit 1, Visit 2, Visit 5, Visit 7 Visit 
10, and Visit 11.  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 11.6). 
A systolic blood pressure >140mm Hg or a diastolic blood pressure >90mm Hg is considered 
abnormal and therefore must be defined as CS or NCS on the CRFs. 
11.2. 
Other Evaluations 
11.2.1. 
Demographic/Medical History 
At Visit 1, the investigator or designee will collect demographic information including date of 
birth, sex at birth, race, and ethnicity for each subject. 
At Visit 1, the investigator must determine each subject’s Fitzpatrick Skin Type and document 
appropriately on the subject’s source document and CRF. 
Table 6: 
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) 


Protocol A-101-SEBK-402 
 
 
 
 
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Skin Type Classification 
Description 
Type VI 
Never burns, never tans (deeply pigmented dark brown to darkest brown) 
11.3. 
Adverse and Serious Adverse Events 
11.3.1. 
Definition of Adverse Events 
An adverse event (AE) is any untoward medical occurrence in a subject 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 preexisting conditions. 
• 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 
subject from the study, requires medical treatment or further diagnostic work up, or is 
considered by the study investigator to be clinically significant. 
The investigator must, for any target or non-target SK related AE, question the subject in detail 
to determine if there are any confounding factors (e.g., irritation by clothing or activity, sunburn) 
for any such AE.  
The investigator should, when certain, report a diagnosis rather than the signs, symptoms or 
clinically relevant abnormal laboratory values associated with the AE. Otherwise, signs, 
symptoms or abnormal laboratory values may be used to describe the AE. 
The investigator must start reporting non-serious AEs starting with the subject’s first study 
medication treatment continuing through Visit 11.   
11.3.2. 
Serious Adverse Event (SAE) 
A serious adverse event is any untoward medical occurrence that at any dose results in one or 
more of the following: 
• Results in death 


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• It is immediately life-threatening 
• It requires in-patient hospitalization or prolongation of existing hospitalization 
• It results in persistent or significant disability or incapacity 
• Results in a congenital abnormality or birth defect 
• It is an important medical event that may jeopardize the subject or may require medical 
intervention to prevent one of the outcomes listed above. 
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. 
11.4. 
Relationship to Study Drug 
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). 
11.5. 
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. 


Protocol A-101-SEBK-402 
 
 
 
 
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Intensity will be assessed according to the following scale: 
• Mild - Awareness of sign or symptom, but easily tolerated 
• Moderate - Discomfort sufficient to cause interference with normal activities 
• Severe - Incapacitating, with inability to perform normal activities 
11.6. 
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 if applicable at Visit 5 and Visit 7 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.  
Non-serious AEs should be recorded starting with the subject’s first study medication treatment 
at Visit 2 and continuing through Visit 11.   
All SAEs regardless of relationship to study medication must be collected and reported to Aclaris 
Therapeutics, Inc. from the time the Informed Consent is signed through Visit 11.   
Upon becoming aware of a SAE the investigator must: 
1. Take the appropriate medical action to ensure the subject’s safety 
2. Immediately inform the Safety Monitor of the SAE: 
 
Ken Kostenbader, MD 
Aclaris Therapeutics, Inc. 
640 Lee Road, Suite 200 
Wayne, PA 19087 
Telephone:  484-848-7012 
Serious Adverse Event Facsimile:  484-324-2359 
Email:  kkostenbader@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 SAE reaches a 
clinically stable outcome with or without sequelae AND the investigator and Safety 
Monitor agree that the SAE is satisfactorily resolved. 
5. Inform the Safety Monitor of SAE updates by telephone followed by an SAE form update 
sent by fax or by e mail. 


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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). 
11.7. 
Withdrawal Due to an Adverse Event 
Any subject who experiences an adverse event may be withdrawn from study drug at any time at 
the discretion of the investigator.  If a subject 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 subject 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 
subject is referred to the care of a local health care professional.  The investigator must inform 
the medical monitor as soon as possible of all subjects who are being considered for withdrawal 
due to adverse events.  Additional reports must be provided when requested. 


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12. 
STATISTICS 
Statistical Analysis of Efficacy 
Descriptive statistics will be used to summarize the data for this study.  The focus of the analyses 
will be the evaluation of the relationship between lesion outcomes and subject satisfaction scores 
from each of the subject satisfaction scales.  Because satisfaction is assessed on a subject level 
and not for each individual lesion, it will be necessary to first summarize multiple lesion 
outcomes into one score for each subject visit.  The analyses will then be implemented at each 
applicable visit by calculating separate Pearson correlations coefficients between (1) mean 
change from baseline in per-subject averaged PLA scores across all lesions, and (2) each subject 
satisfaction scale score at the visit.  As a sensitivity analysis, the above statistics will also be 
calculated using Spearman’s rank-order correlation.  Exploratory analyses similar to the above 
will also be conducted between (1) per-subject averaged percent of treated lesions clear (PLA = 
0) and (2) each subject satisfaction scale score.  A similar exploratory analysis will also be 
conducted using per-subject averaged percent of lesions clear or near-clear (PLA < 2).  
Additional multiple regression models may be used across groups of subject satisfaction scales, 
depending on the pattern of individual subject satisfaction scale outcomes. 
 
Statistical Analysis of Safety Data 
Descriptive statistics will be calculated on the safety parameters using the ITT population. The 
proportion of subjects with adverse events related to study medication will be tabulated and 
presented by treatment and Medical Dictionary for Regulatory Activities (MedDRA) System 
Organ Class. Vital signs, and clinically relevant abnormal laboratory results will also be 
tabulated and presented. No inferential testing will be performed. 
Safety summaries will include listings 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 showing the proportion of subjects experiencing adverse events, 
both overall and by MedDRA System Organ Class. 
Interim Analysis 
An interim Analysis will not be conducted for this study. 


Protocol A-101-SEBK-402 
 
 
 
 
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13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
13.1. 
Study 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. representative, designee and/or 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. 
13.2. 
Audits and Inspections 
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 Aclaris Therapeutics, Inc. or its 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. 
The investigator should contact Aclaris Therapeutics, Inc. immediately if contacted by a 
regulatory agency about an inspection. 
13.3. 
Institutional Review Board (IRB) 
This protocol and any accompanying material, including information that will be provided to 
prospective subjects (such as advertisements, subject information sheets, or study descriptions 
used to induce study participation or obtain informed consent) must be submitted to the 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 subjects 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 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 subjects.  In the latter case, the IRB must be notified promptly, and their written approval 
must be obtained as soon after the fact as possible. 


Protocol A-101-SEBK-402 
 
 
 
 
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Appropriate reports on the progress of the study will be made to the IRB and the Sponsor by the 
Investigator in accordance with applicable regulatory regulations and in conformity with policies 
established by both the 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 IRB as soon as possible, and in accordance with the guidelines of the 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 
subject 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 subject’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 subject.  The investigational site must retain the original 
signed consent and provide a copy to the subject. 


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14. 
QUALITY CONTROL AND QUALITY ASSURANCE 
14.1. 
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 subjects or when the change involves only logistics or 
administration.  The principal investigator and the sponsor will sign the protocol amendment. 
14.2. 
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.   
A protocol violation is defined as any divergence from the protocol-specific inclusion/exclusion 
criteria, subject is administered a prohibited medication during the active protocol treatment 
period, primary objective variable criteria, and/or GCP guidelines.  Protocol violations will be 
identified and recorded, by study center personnel, on the CRF. 
As a matter of policy, sponsor/CRO will not grant exceptions to protocol-specific entry criteria 
to allow subjects to enter a study.  If under extraordinary circumstances such action is considered 
ethically, medically, and scientifically justified for a particular subject, prior approval from 
sponsor/CRO and the responsible IRB/IEC, in accordance with the Sponsor/CROs Standard 
Operating Procedure (SOP), is required before the subject will be allowed to enter the study.  If 
investigative center personnel learn that a subject 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 
14.3. 
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 investigator site file to each center. 


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15. 
ETHICS 
15.1. 
Ethical Conduct of the Study 
The Sponsor will use information developed in this clinical study in connection with the 
development of A-101 40% 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 subjects’ 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 subject information.  To assure that subjects’ confidentiality is maintained, 
subjects’ data will be identified by a study-assigned number and date of birth only. 
All Sponsor personnel will handle subjects’ 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 and the subject’s date of 
birth. 
15.2. 
Written Informed Consent 
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 3.  A written, signed informed consent form (ICF) must be obtained from each 
subject prior to performing any study related procedure (e.g., vital signs, clinical laboratory 
sampling, or photography). 
The Principal Investigator at each center will ensure that the subject is given full and adequate 
oral and written information about the nature, purpose, possible risk and benefit of the study.  
Subjects must also be notified that they are free to discontinue from the study at any time.  The 
subject should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The subject’s signed and dated informed consent must be obtained before conducting any study 
procedures. 
The Principal Investigator must maintain the original, signed Informed Consent Form.  A copy of 
the signed Informed Consent Form must be given to the subject. 
 


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16. 
DATA HANDLING AND RECORDKEEPING 
16.1. 
Inspection of Records 
Aclaris Therapeutics, Inc. will be allowed to conduct site visits to the investigation facilities for 
the purpose of monitoring any aspect of the study.  The Investigator agrees to allow the monitor 
to inspect the drug storage area, study drug inventory, drug accountability records, subject charts 
and study source documents, and other records relative to study conduct. 
16.2. 
Data Management 
Data will be collected using CRFs that are specifically designed for this study.  The data 
collected on the CRFs will be captured in a clinical data management system (CDMS) that meets 
the technical requirements described in US 21 Code of Federal Regulations (CFR) Part 11.  The 
CDMS will be fully validated to ensure that it meets the scientific, regulatory, and logistical 
requirements of the study before it is used to capture data from this study.  Before using the 
CDMS, all users will receive training on the system and study specific training.  After they are 
trained, users will be provided with individual system access rights. 
The handling of data, including data quality assurance, will comply with regulatory guidelines, 
including ICH and GCP, and the sponsor/CRO SOPs and working instructions.  Data 
management and control processes specific to this study will be described in a data management 
plan.  At the end of the study, the database will be locked, and the data will be released for 
reporting and statistical analysis. 
16.3. 
Regulatory Documents 
The investigator must maintain a study file containing current and complete regulatory 
documentation in compliance with the current ICH E6 GCP guideline. This file will be reviewed 
as part of the routine monitoring for this study. 
16.4. 
Contractual Requirements 
A contractual agreement will be signed between Aclaris Therapeutics, Inc. and each investigator.  
This document will contain supplemental information, including financial terms, confidentiality, 
study schedule, third party responsibility, and publication rights. 
16.5. 
Retention of Records 
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 


Protocol A-101-SEBK-402 
 
 
 
 
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investigator must notify Aclaris Therapeutics, Inc., in writing, of the name and address of the 
new individual. 
If the Investigator cannot guarantee this archiving requirement at the investigative site for any or 
all of the documents, special arrangements must be made between the Investigator and the 
Sponsor to store these in sealed containers in an off-site storage location so that they can be 
returned to the Investigator in case of a regulatory audit.  Where source documents are required 
for the continued care of the subject, appropriate copies will be made for off-site storage. 
No trial document should be destroyed without prior written agreement between the Sponsor and 
the Investigator. Should the Investigator wish to assign the trial records to another party or move 
them to another location, the Investigator must notify the Sponsor in writing of the new 
responsible person and/or the new location 


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17. 
LIST OF REFERENCES 
Chan HP, Maibach HI,. 2008. "Hydrogen Peroxide, Blanching, and Skin: an Overview." Cutaneous and 
Ocular Toxicology 307-309. 
Ellers S, Bach D, Gaber, BS et al. 2013. "Accuracy of Self-report in Assessing Fitzpatrick Skin Phototypes 
I through VI." JAMA Dermatology 1289-1294. 
G, Zonios. 2007. "Probing Skin Interactionwith Hydrogen Peroxide Using Diffuse Reflectance 
Spectroscopy." Physicis in Medicine and Biology 269-278. 
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. 
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. 
RJ, 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. 
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. 


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18. 
APPENDICES 


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APPENDIX 1.  
A-101-SEBK-402 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 
• 
Continue your routine cosmetics and skin care products 
• 
Avoid exposing your target and non-target SKs to excessive natural or artificial ultraviolet 
radiation (e.g., sunlight, tanning beds) and use sunscreen on the target or non-target SKs, 
if excessive exposure cannot be avoided 
• 
The use of the following therapies to treat any of the target or non-target lesions are 
prohibited 
o Retinoids (topical) 
o Corticosteroids (topical) 
o LASER, light or other energy-based therapy 
o Liquid nitrogen, electrodesiccation, curettage, imiquimod, ingenol mebutate 
o Microdermabrasion or superficial chemical peels 
o Antibiotics (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 or non-target SKs, 
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 or non-target SKs for at least 6 hours 
o Apply any topical products to the target or non-target SKs for at least 6 hours. 


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STUDY VISIT SCHEDULE: 
VISIT 2: 
Date:                            Time: 
VISIT 3: 
Date:                            Time: 
VISIT 4: 
Date:                            Time: 
VISIT 5: 
Date:                            Time: 
VISIT 6: 
Date:                            Time: 
VISIT 7: 
Date:                            Time: 
VISIT 8: 
Date:                            Time: 
VISIT 9: 
Date:                            Time: 
VISIT 10: 
Date:                            Time: 
VISIT 11: 
Date:                            Time: 
Thank you for following these instructions 
 


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APPENDIX 3.  
 
 
 


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SAP_001.pdf: 
 
 
 
STATISTICAL ANALYSIS PLAN 
Protocol Number: A-101-SEBK-402 
AN OPEN-LABEL STUDY ASSESSING SUBJECT SATISFACTION 
WITH A-101 HYDROGEN PEROXIDE TOPICAL SOLUTION, 40% 
(W/W) TREATMENT FOR SEBORRHEIC KERATOSES OF THE 
FACE, NECK, AND DECOLLETAGE (SK-FAN) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This document is a privileged and confidential communication of Aclaris Therapeutics, Inc. Acceptance of this 
document constitutes an agreement by the recipient that no unpublished information contained herein will be 
used, published or disclosed without prior written approval from Aclaris Therapeutics, Inc. 
 
 




Aclaris Therapeutics, Inc. 
 
 
SAP for Protocol Number: A-101-SEBK-402 
 
 
 
 
 
Page 3 of 16 
Date: 13-Dec-2018 
 
Table of Contents 
1 
STUDY OBJECTIVES AND SAMPLE SIZE RATIONALE ...................................6 
1.1 
STUDY OBJECTIVES ................................................................................................6 
1.1.1 
Primary Objective .....................................................................................................6 
1.1.2 
Secondary Objectives ...............................................................................................6 
1.1.3 
Safety Assessments ...................................................................................................6 
1.2 
SAMPLE SIZE .............................................................................................................6 
2 
STUDY DESIGN SUMMARY .....................................................................................7 
2.1 
VISITS ..........................................................................................................................7 
2.2 
SUBJECTS .................................................................................................................10 
2.2.1 
Number of Subjects ................................................................................................10 
2.2.2 
Diagnosis and Main Criteria for Inclusion .............................................................10 
2.2.3 
Study Population Characteristics ............................................................................10 
2.2.4 
Replacement Subjects .............................................................................................10 
2.3 
TREATMENT AND RANDOMIZATION ...............................................................10 
2.3.1 
Study Medications, Treatment, and Mode of Administration ................................10 
2.3.2 
Randomization ........................................................................................................10 
2.3.3 
Administration of Treatment ..................................................................................10 
2.3.4 
Duration of Treatment ............................................................................................11 
2.4 
ASSESSMENTS ........................................................................................................11 
2.4.1 
Evaluators ...............................................................................................................11 
2.4.2 
Evaluations – Efficacy ............................................................................................11 
2.4.2.1 
Physician’s Lesion Assessment (PLA) ................................................................11 
2.4.2.2 
SK Dimensions ....................................................................................................12 
2.4.2.3 
Subject Satisfaction Assessment .........................................................................12 
2.4.3 
Evaluations – Safety ...............................................................................................12 
2.4.3.1 
Adverse Events ....................................................................................................12 
2.4.3.2 
Vital Signs ...........................................................................................................12 
2.4.4 
Other Evaluations ...................................................................................................13 


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Date: 13-Dec-2018 
3 
STATISTICAL METHODOLOGY ..........................................................................14 
3.1 
GENERAL STATISICAL CONSIDERATIONS ......................................................14 
3.2 
ANALYSIS POPULATION AND DISPOSITION OF SUBJECTS .........................14 
3.2.1 
Data Sets Analyzed .................................................................................................14 
3.2.2 
Disposition of Subjects ...........................................................................................14 
3.3 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS .....................14 
3.4 
MEDICAL HISTORY................................................................................................14 
3.5 
PRIOR/CONCOMITANT MEDICATIONS .............................................................15 
3.6 
STUDY DRUG EXPOSURE AND COMPLIANCE ................................................15 
3.7 
EFFICACY ANALYSIS – PLA ANALYSES...........................................................15 
3.8 
SAFETY ANALYSIS ................................................................................................16 
3.8.1 
Adverse Events .......................................................................................................16 
3.8.2 
Vital Signs ...............................................................................................................16 
 


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Date: 13-Dec-2018 
List of Abbreviations 
Abbreviations/Acroynms 
AE 
adverse event 
ATC 
antomical therapeutic chemical 
CS 
clinically significant 
CSR 
clinical study report 
CRF 
case report form 
Max 
maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
Min 
minimum 
mm 
millimeters 
NCS 
non-clinically significant 
NDA 
new drug application 
PLA 
physician’s lesion assessment 
PT 
preferred term 
SAE 
serious adverse event 
SK 
seborrheic keratosis 
Std Dev 
standard deviation 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
 


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Date: 13-Dec-2018 
1 
STUDY OBJECTIVES AND SAMPLE SIZE RATIONALE 
1.1 
STUDY OBJECTIVES 
The rationale for this study is to assess subject satisfaction after treatment with A-101 solution 
40% (w/w) on Seborrheic Keratosis (SKs) of the face, neck, and décolletage.  Subjects will be 
naive to A-101 (Hydrogen Peroxide) Topical Solution, 40% (w/w) treatment.  Dermatologists 
identify 3 eligible target SKs on each subject; 2 target SKs must be on the face, and the 
additional 1 target SK must be on the neck or décolletage.  Up to 4 additional non-target SKs 
may be identified on the face, neck or décolletage.  This study is the first post-marketing study 
after the successful New Drug Application (NDA) and product launch for A-101 solution 
applied to SK lesions.  Protocol provides a more detailed description of the study.  Primary 
and Secondary Objectives are summarized below. 
1.1.1 
Primary Objective 
Subject satisfaction after treatment with A-101 (Hydrogen Peroxide) topical solution, 40% 
(w/w) at Day 85 and Day 113. 
1.1.2 
Secondary Objectives 
• Effectiveness of treatment as measured by the Physician’s Lesion Assessment (PLA) at 
Day 85 and Day 113. 
• Comparison of the PLA score(s) to treatment satisfaction at Day 85 and Day 113. 
1.1.3 
Safety Assessments 
Safety assessments include adverse events, change in vital signs, and concomitant medication 
use. 
1.2 
SAMPLE SIZE 
A total of 30 subjects are planned to enroll in the study. 
 
 


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2 
STUDY DESIGN SUMMARY 
This study is an open-label study designed to evaluate subject’s satisfaction after treatment of 
seborrheic keratoses with A-101 40%.  Dermatologists (investigators) identify 3 eligible target 
SKs on each subject; 2 target SKs must be on the face, and the additional 1 target SK must be 
on the neck or décolletage.  Up to 4 additional non-target SKs may be identified on the face, 
neck or décolletage.  Each target and non-target SK will be treated during up to 3 separate 
treatment visits: Visit 2, Visit 5, and Visit 7. Each SK must be treated by a study trained 
healthcare provider at the site.  Retreatment of identified target and non-target SKs will be 
determined by the physician using the PLA.  Each application will last up to 20 seconds with 
about 60 seconds between applications. 
2.1 
VISITS 
Subjects will be required to complete a total of 11 study visits.  The protocol defined study 
visits are: 
• Visit 1 (Day -13 - 0) Screening 
• Visit 2 (Day 1) Study Medication Treatment 
• Visit 3 (Day 2) Follow-up Visit 
• Visit 4 (Day 8) Follow-up Visit 
• Visit 5 (Day 15) Study Medication Treatment (if PLA ≥ 1) 
• Visit 6 (Day 22) Follow-up Visit 
• Visit 7 (Day 29) Study Medication Treatment (if PLA ≥ 1) 
• Visit 8 (Day 36) Follow-up Visit 
• Visit 9 (Day 57) Follow-up Visit 
• Visit 10 (Day 85) Follow-up Visit 
• Visit 11 (Day 113) Follow-up Visit; End of Study 
Study flow chart is as below. 
 


Aclaris Therapeutics, Inc. 
 
 
SAP for Protocol Number: A-101-SEBK-402 
 
 
 
 
 
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Study Design and Schedule of Assessments 
 
Visit 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
Treatment Day 
Day -13 - 0 
Day 1 
Day 2 
Day 8 
Day 15 
Day 22 
Day 29 
Day 36 
Day 57 
Day 85 
Day 113 
Visit Window 
N/A 
N/A 
N/A 
± 1 day 
± 1 day 
± 1 day 
± 1 day 
± 1 day 
± 7 days 
± 7 days 
± 7 days 
Informed Consent 
X 
Inclusion/ Exclusion1 
X 
X 
Subject Identifier2 
X 
Dermatological Medical History 
X 
Demographics 
X 
Fitzpatrick Skin Type Assessment3 
X 
Vital Signs4 
X 
X 
X 
X 
X 
X 
Prior Medications/Therapies5 
X 
Target and Non-Target 
SK Identification6 
X 
Physician’s Lesion Assessment7 
X 
X 
X 
X 
X 
X 
X 
X 
SK Dimensions8 
X 
X 
X 
X 
X 
X 
X 
X 
SK Photography9 
X 
X10 
X11 
X 
X10 
X 
X
10 
X 
X 
X 
X 
Study Medication Application12 
X 
X 
X 
Subject Satisfaction Assessment13 
X 
X 
X 
X 
X 
X 
Concomitant Therapies14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events15 
X 
X 
X 
X 
X 
X 
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SAP for Protocol Number: A-101-SEBK-402 
 
 
 
 
 
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1 Subject inclusion/exclusion criteria will be reassessed prior to enrollment during Visit 2. 
2 Investigational sites will assign a unique five-digit subject identifier to each subject at Visit 1, formatted as NN-NNN where the first 2 digits are the site number, and the final 3 digits are the 
subject number that must be assigned in ascending numerical order (using leading zeroes, as appropriate). This subject identifier will be used in all study documentation for the duration of the 
study. 
3 Each subject’s skin must be assessed during Visit 1 using the Fitzpatrick Skin Type Assessment.  Refer to Table 6 for the scale. 
4 Vital 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, Visit 5, Visit 7, 
Visit 10, and Visit 11. 
5 Prior medications/therapies will be collected for a time-period of 13 days prior to Visit 1. Refer to Section 8.4 for a list of permitted and restricted concomitant medications. 
6 The treating investigator will identify 3 target SKs and up to 4 non-target SKs.  Two (2) target SKs must be on the face, and the additional 1 target SK must be on the neck or décolletage. The 
4 non-target SKs may be located on the face, neck, or décolletage. 
7 The investigator will use the Physician’s Lesion Assessment (PLA) to assess the severity of each target and non-target SKs at Visits 1, 2, 3, 4, 5, 7, 10, and 11. At Visit 2, Visit 5 and Visit 7, 
the investigator must assess each target and non-target SK prior to application of the study medication.  In order to be eligible for enrollment to the study during Visit 2, the subject must have 
a PLA grade ≥ 2 for each target and non-target SK. 
8 The investigator will measure the dimensions of each target and non-target SK at Visits 1, 2, 3, 4, 5, 7, 10 and 11.  At Visit 2, Visit 5 and Visit 7, the investigator must measure each target and 
non-target SK prior to application of the study medication.  In order to be eligible for enrollment to the study during Visits 1 and 2, each target SK must have a diameter that is between ≥ 5 
and ≤ 15 mm (inclusive) and be raised.  In order to be eligible for enrollment to the study during Visits 1 and 2, each non-target SK must be a raised SK.  At Visits 3, 4, 5, 7, and 10 the 
investigator must assess the thickness of each target and non-target SK above the surrounding skin. Additional target and non-target SK requirements are outlined in Protocol Section 10.1. 
9 Each target and non-target SK will be photographed at all study visits using the Aclaris Therapeutics, Inc. supplied photography equipment. 
10 During Visit 2 each target and non-target SK will be photographed prior to the application of A-101 40%, 10 minutes post application (+2 minutes), and 1-hour post application (± 10 
minutes).  During Visit 5 and Visit 7, the target and non-target SKs will be photographed prior to the application of A-101 40%, if applicable.  
11 During Visit 3 each target and non-target SK will be photographed 24-hours post application during Visit 2 (± 2 hours). 
12 A-101 40% will be applied to each target and non-target SK by a study trained healthcare provider at the site. Each target and non-target SK will be treated with A-101 40% following 
confirmation of subject eligibility and study enrollment at Visit 2. If a target or non-target SK meets the criteria for retreatment as defined in Section 9.5, the SK will be retreated at Visit 5 
and Visit 7. Following application of A-101 40%, subjects must NOT wash/submerge a target and non-target SK for at least 6 hours and they must NOT apply any topical products to any 
target or non-target SK for at least 6 hours. 
13 Subjects will be asked to assess how satisfied they are with the treatment experience they received for the target and non-target SKs at the specified visits.  On Visit 2 the subject will 
complete the assessment prior to application of A-101 40%. On Visit 3 the subjects will complete the assessment approximately 24 hours after the treatment.  On Visit 6 and Visit 8 the 
subjects will complete the assessment approximately 1 week after the treatment, only if the subject received treatment on Visit 5 or Visit 7. The subject will complete the assessment during 
the Visit 10 and Visit 11. 
14 All concomitant therapies including (topical and oral) prescription medications, over the counter medications, 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 and non-target SKs 
within 12 hours prior to any study visit. 
15 The reporting period for SAEs begins when the subject signs the informed consent form.  Refer to Protocol Section 11.6 for instructions on the reporting of SAEs.  Non-serious clinical 
adverse events will be collected following the application of the study medication at Visit 2 and continue through Visit 11. All safety reporting (AEs and SAEs) will conclude at Visit 11. 
 


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SAP for Protocol Number: A-101-SEBK-402 
 
 
 
 
 
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Date: 13-Dec-2018 
2.2 
SUBJECTS 
2.2.1 
Number of Subjects 
A total of 30 subjects will be treated on the study at 3 investigational sites in US. 
2.2.2 
Diagnosis and Main Criteria for Inclusion 
Subjects will be SK treatment naïve males and females between age of 30 and 75 years old 
with stable clinically typical SK.  For each subject, 3 eligible target SKs; 2 target SKs must be 
on the face, and the additional 1 target SK must be on the neck or décolletage.  Up to 4 
additional non-target SKs may be identified on the face, neck or décolletage. 
2.2.3 
Study Population Characteristics 
Subjects with a clinical diagnosis of SK who meet all the inclusion criteria and none of the 
exclusion criteria will be eligible to enroll in the study.  Detailed inclusion and exclusion 
criteria, see protocol sections 7.1 and 7.2.  
2.2.4 
Replacement Subjects 
If a subject is enrolled to the study but does not receive a dose of study drug, then the subject 
may 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 enrolled under using the same 
subject identifier and must sign a new informed consent form. 
2.3 
TREATMENT AND RANDOMIZATION 
2.3.1 
Study Medications, Treatment, and Mode of Administration 
A-101 Solution, 40% (w/w), external topical. 
2.3.2 
Randomization 
Not applicable. 
2.3.3 
Administration of Treatment 
At Visits 2, 5, and 7, each target and non-target SK must be treated by a study trained 
healthcare provider at the site. 


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At Visits 5 and 7, all identified target and non-target SKs that have a PLA grade of ≥ 1 will be 
retreated with the solution.  If in the investigator’s opinion, the lesion is not appropriate for re-
treatment, treatment will be withheld. 
2.3.4 
Duration of Treatment 
The duration of the study participation is anticipated to be a maximum of 134 days per subject.  
The final visit (Visit 11), has a maximum allowable visit window of 7 days. 
2.4 
ASSESSMENTS 
2.4.1 
Evaluators 
The investigator, a designated and appropriately trained staff member (e.g., sub investigator) 
or the subject will perform the study assessments according to the defined schedules. 
Similar lighting conditions and subject positioning should be used for all evaluations for a 
given subject. 
2.4.2 
Evaluations – Efficacy 
2.4.2.1 
Physician’s Lesion Assessment (PLA) 
The PLA is the investigator’s assessment of the severity of the target and non-target SK at a 
particular time point.  The investigator may refer to other evaluations (e.g., prior photographs) 
to assist with these assessments. 
At Visits 1, 2, 3, 4, 5, 7, 10, and 11 the investigator will assess the target and non-target SK 
using the scale below and report the one integer that best describes the severity of the target or 
non- target SK.  At Visit 2 and if applicable at Visit 5 and Visit 7, the investigator must 
complete the PLA prior to the study medication treatment.  The description of PLA grade is as 
shown in the table below. 
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) 


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In order for a subject to be eligible for screening and enrollment to the study, each target and non- 
target SK must have a PLA grade of ≥ 2. 
2.4.2.2 
SK Dimensions 
At Visit 1 and Visit 2 prior to study enrollment, the investigator will measure the diameter 
and thickness of each target and non-target SK using the ruler provided. 
The investigator must measure the diameter of the longest axis of each target and non-target 
SK in millimeters (mm) as follows: 
• Diameter (i.e., the length of the longest axis) 
• Thickness (height above the surrounding skin) 
The PLA (the thickness) of the target and non-target SKs will be measured by the investigator 
at Visits 3, 4, 5, 7, 10, and 11.  When the visit coincides with treatment (Visits 2, 5 and 7), the 
thickness must be measured prior to the application of study medication. 
2.4.2.3 
Subject Satisfaction Assessment 
Subjects will be asked to assess their level of satisfaction regarding the study medication 
treatment experience.  The subject survey will be completed at Visits 2, 3, 6 (only if treated at 
Visit 5), 8 (only if treated at Visit 7), 10, and 11. 
The subject satisfaction assessments contain single and multiple choice questions.  Three sets 
of questionnaires are designed for assessments at Day 1/Visit 2 prior to treatment, assessments 
for treatment experience after each treatment, and assessments at the end of study. 
2.4.3 
Evaluations – Safety 
2.4.3.1 
Adverse Events 
Non-serious AEs will be recorded starting with the subject’s first study medication treatment 
at Visit 2 and continuing through Visit 11.  All SAEs regardless of relationship to study 
medication will be collected and reported from the time the Informed Consent is signed 
through Visit 11. 
2.4.3.2 
Vital Signs 
Vital signs will be measured by a qualified staff member at Visit 1, Visit 2, Visit 5, Visit 7 
Visit 10, and Visit 11.  The following items will be measured: 
• Body temperature 
• Pulse rate 


Aclaris Therapeutics, Inc. 
 
 
SAP for Protocol Number: A-101-SEBK-402 
 
 
 
 
 
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Date: 13-Dec-2018 
• 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. 
A systolic blood pressure >140mm Hg or a diastolic blood pressure >90mm Hg is considered 
abnormal and therefore must be defined as CS or non-clinically significant (NCS) on the Case 
Report Forms (CRFs). 
2.4.4 
Other Evaluations 
At Visit 1, the investigator or designee will collect demographic information including date of 
birth, sex at birth, race, ethnicity, and Fitzpatrick Skin Type for each subject. 
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) 
 
 
 


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3 
STATISTICAL METHODOLOGY 
This plan describes methods planned for the analysis and display of efficacy (PLA-based 
analyses only) and safety endpoints.  Summaries will be based on mainly descriptive 
summaries for each assessment.  A separate analysis plan will detail the analysis methods used 
for analyzing subject satisfaction assessments and its relationship with PLA. 
3.1 
GENERAL STATISICAL CONSIDERATIONS 
Descriptive statistics (mean, standard deviation [Std Dev], median, minimum [Min], and 
maximum [Max]) will be used for continuous variables; number and percentage of subjects 
will be used for discrete variables.  In general, the last measurement prior to the first dose of 
study treatment will be used as the baseline value.  Nominal visits will be used for by-visit 
summaries. 
All tabulations of summary statistics, graphical presentations, and statistical analyses will be 
performed using SAS® Version 9.2 or higher. 
3.2 
ANALYSIS POPULATION AND DISPOSITION OF SUBJECTS 
3.2.1 
Data Sets Analyzed 
Intent-to-Treat (ITT) analysis set includes all enrolled subjects.  This is the analysis set for all 
analyses.  A subject is considered enrolled if at least one study treatment is applied. 
3.2.2 
Disposition of Subjects 
The numbers of subjects screened (ie, signed informed consent), enrolled, discontinued from 
treatment (by reason), and replaced will be presented. 
3.3 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic and baseline characteristics will be summarized.  Gender, race, ethnicity, and 
Fitzpatrick skin type will be summarized with number and percentage presented for each 
category.  Age, height, weight will be described with summary statistics (n, mean, Std Dev, 
median, minimum, and maximum). 
3.4 
MEDICAL HISTORY 
Medical history will be summarized by body system class. 


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3.5 
PRIOR/CONCOMITANT MEDICATIONS 
The number and percentage of prior medications, and concomitant medications will be 
summarized by Antomical Therapeutic Chemical (ATC) and preferred term (PT) separately. 
Medications taken any time prior to the first study treatment are counted as prior medications.  
Those taken any time on or after the first application of study medication through 30 days 
after the last application of study are counted as concomitant. 
Subject will be counted only once within each classification.  The same subject may contribute 
to two or more preferred terms within the same ATC classification. 
3.6 
STUDY DRUG EXPOSURE AND COMPLIANCE 
Duration of treatment (Last study treatment application date – First study treatment 
application date + 1) will be summarized descriptively.  Number and percentage of subjects at 
each visit will be summarized by the number of target/non-target lesions being treated.  In 
addition, number and percentage of subjects with re-treatment will be summarized for the 
applicable visits. 
3.7 
EFFICACY ANALYSIS – PLA ANALYSES 
PLA related parameters will be summarized at lesion level and at subject level. 
At each visit or applicable visit, the following analyses will be performed: 
• Number and percentage of lesions by PLA score categories (clear, near-clear, thin, and 
thick), overall and by target/non-target lesions; separately for face target lesions, and 
for neck target lesions; 
• Summary statistics on PLA score (mean of all lesions, mean of target lesions, and non-
target lesions, respectively); 
• Summary statistics on percentage of lesions that are clear (PLA=0); separately for face 
target lesions, and for neck target lesions; 
• Summary statistics on percentage of lesions that are clear or near clear (PLA=0 or 1); 
separately for face target lesions, and for neck target lesions; 
• Number and percentage of lesions by location (face, neck, or décolletage), overall and by 
target/non-target lesions; 


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SAP for Protocol Number: A-101-SEBK-402 
 
 
 
 
 
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3.8 
SAFETY ANALYSIS 
The safety and tolerability of the investigational products will be determined by reported AEs, 
and vital signs. 
3.8.1 
Adverse Events 
All subjects will be assessed regularly for the potential occurrence of adverse events (AEs) 
from the date of informed consent to 30 days after the last study treatment.  The incidence of 
treatment-emergent AEs (TEAEs) will be summarized and tabulated using MedDRA (version 
22.0), by System Organ Class (SOC) and Preferred Term (PT).   
An overview of adverse events for the ITT analysis set will be provided, summarizing the 
incidence of the following: 
• 
Count of TEAEs; 
• 
Subjects with TEAEs; 
• 
Count of Treatment-emergent serious AEs (TESAE); 
• 
Subjects with TESAE; 
• 
TEAE by maximum severity; 
• 
TESAE by maximum severity; 
• 
Subjects with TEAEs that lead to discontinuation of study; 
• 
Subjects with TESAEs that lead to discontinuation of study; 
• 
Subjects with Related TEAEs; 
• 
Subjects with Related TESAEs. 
3.8.2 
Vital Signs 
Vital signs measurements include pulse rate, temperature, systolic blood pressure, and 
diastolic blood pressure.  Measures at baseline and changes from baseline to visit will be 
summarized.  In addition, the maximum and minimum post-treatment values and their changes 
from baseline will be summarized.  The number and percentage of subjects with abnormal 
blood pressure will be summarized.