Clinical trial NCT01986920
Conditions: Seborrheic Keratosis (SK)
Keywords: SK Seborrheic Keratosis
Sponsor: Aclaris Therapeutics, Inc.
Start date: 2013-10-22; Completion date: 2014-02-25
Enrollment: 35 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Evaluate the safety, tolerability of A-101 when applied to seborrheic keratosis lesions on the back of subjects.

Detailed description:
The main objective of this study is to evaluate the safety, effectiveness and tolerability of three concentrations of A-101 25%, 32.5%, and 40%, when applied to individual seborrheic keratosis target lesions on the back compared with a matching A-101 vehicle.

Arms: arm 1: Low dose group arm 2: Mid Dose Group arm 3: High Dose Group arm 4: Placebo group
Interventions: intervention 1: A-101 25% intervention 2: A-101 32.5% intervention 3: A-101 40% intervention 4: A-101 Vehicle
Intervention descriptions: intervention 1: Low Dose Concentration of A-101 applied to one of 4 Target Lesions intervention 2: Mid Dose Concentration of A-101 applied to one of 4 Target Lesions intervention 3: High Dose Concentration A-101 applied to one of 4 Target Lesions intervention 4: Placebo applied to one of 4 Target Lesions

Protocol documents:
Prot_SAP_000.pdf: 
A-101-SEBK-201 Clinical Study Report 
 
Aclaris Therapeutics, Inc. 
 
 
 
Appendix 16.1.1 
Protocol and Protocol Amendments 
16.1.1.1 
Protocol Amendment Number 1 Summary of Changes (24 September 2013) 
16.1.1.2 
Protocol Amendment Number 2 Summary of Changes (5 November 2013) 
16.1.1.3 
Revised Protocol Number 1 (incorporates Amendment Numbers 1 and 2; 
5 November 2013) 
 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 1 
Page 1 of 5 
Date: 24-SEP-2013                                                                                                                 Supersedes: NEW                     
 
CLINICAL STUDY PROTOCOL 
 
Protocol Number: A-101-SEBK-201 
Amendment Number 1 
 
A RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED, WITHIN SUBJECT 
COMPARISON STUDY OF THE SAFETY, TOLERABILITY AND EFFECTIVENESS 
OF A-101 TOPICAL SOLUTION IN SUBJECTS WITH SEBORRHEIC KERATOSIS  
 
 
 
Sponsor 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Telephone: (484) 324-7933 
Facsimile: (484) 320-2344 
 
Study Contact 
Brian B. Beger 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Telephone: (484) 321-5552 
E-mail: bbeger@aclaristx.com 
 
Medical Monitor 
Stuart D. Shanler, M.D. 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Telephone: (484) 321-5555 
Serious Adverse Event facsimile: (484) 324-2359 
E-mail: sshanler@aclaristx.com 
 
 
 
This document is a privileged and confidential communication of Aclaris Therapeutics, Inc. Acceptance of this 
document constitutes an agreement by the recipient that no unpublished information contained herein will be used, 
published or disclosed without prior written approval from Aclaris Therapeutics, Inc. 
 
 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 1 
Page 2 of 5 
Date: 24-SEP-2013                                                                                                                 Supersedes: NEW                     
 
INVESTIGATOR/SPONSOR AGREEMENT 
 
I have read this protocol amendment and agree to conduct this study in compliance 
with the protocol as amended and with any additional amendments. 
 
 
Investigator Signature: 
 
 
 
 ___________________________________  
 _______________________  
<Investigator Name> 
 
Date 
Investigator 
 
 
 
 
 
 
 
 
 
Sponsor Signature: 
 
 
 
 ___________________________________  
 _______________________  
Christopher Powala 
Date 
Chief Operating Officer 
Aclaris Therapeutics, Inc. 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 1 
Page 3 of 5 
Date: 24-SEP-2013                                                                                                                 Supersedes: NEW                     
 
Table of Contents 
1. 
AMENDMENT HISTORY ............................................................................................................ 4 
2. 
AMENDMENT SUMMARY ......................................................................................................... 4 
3. 
AMENDMENT RATIONALE ...................................................................................................... 4 
4. 
PROTOCOL CHANGES ................................................................................................................ 4 
 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 1 
Page 4 of 5 
Date: 24-SEP-2013                                                                                                                 Supersedes: NEW                     
 
1. 
AMENDMENT HISTORY 
Protocol date: 09-SEP-2013 
Previous amendments: None 
 
 
2. 
AMENDMENT SUMMARY 
The following sections of the A-101-SEBK-201 protocol dated 09-SEP-2013, approved by 
Aclaris Therapeutics, Inc. on 09-SEP-2013, are amended: 
 Section 2.1 Summary 
 Section 4.3 Exclusion criteria 
 Section 5.3.2 Visit 2 (Day1) 
 Section 6.1.3 Lesion Dimensions. 
 
 
3. 
AMENDMENT RATIONALE 
These protocol changes are made to: 
 Correct a misspelling in the Exclusion Criteria 
 Clarify the Visit 2 procedures 
 Correct typographical error in the Lesion Dimensions section. 
 
  
4. 
PROTOCOL CHANGES 
Section 2.1 Summary: 
Previous paragraph 3, sentence 1: 
Numerous treatment options exist, and include a plethora of destructive/ablative 
modalities such as liquid nitrogen cryotherapy, electrodessication, lasers… 
 
Changed paragraph 3, sentence 1 (with corrected spelling highlighted): 
Numerous treatment options exist, and include a plethora of destructive/ablative 
modalities such as liquid nitrogen cryotherapy, electrodesiccation, lasers… 
 
 
 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 1 
Page 5 of 5 
Date: 24-SEP-2013                                                                                                                 Supersedes: NEW                     
 
Section 4.3 Exclusion Criteria: 
Previous criterion 4: 
Has used any of the following topical therapies on the treatment area within the specified 
period prior to Visit 1: 
 Retinoids; 90 days 
 Liquid nitrogen, electrodessication, curettage, imiquimod, 5-flurouracil, or ingenol 
mebutate; 60 days 
 Glucocortico-steroids or antibiotics; 14 days 
 Moisturizers/emollients, sunscreens; 12 hours 
 
Changed criterion 4 (with corrected spelling highlighted): 
Has used any of the following topical therapies on the treatment area within the specified 
period prior to Visit 1: 
 Retinoids; 90 days 
 Liquid nitrogen, electrodesiccation, curettage, imiquimod, 5-flurouracil, or ingenol 
mebutate; 60 days 
 Glucocortico-steroids or antibiotics; 14 days 
 Moisturizers/emollients, sunscreens; 12 hours 
 
 
Section 5.3.2 Visit 2 (Day 1): 
Previous item 14, Prior to randomization: 
Have the subject perform a pre-application Local Skin Reaction assessment of the 
symptoms for each target lesion 20 (±4) minutes after the study medication application 
to all target lesions is completed (Section 6.2.1) 
 
Changed item 14, Prior to randomization: 
Have the subject perform a pre-application Local Skin Reaction assessment of the 
symptoms for each target lesion (Section 6.2.1) 
 
 
Section 6.1.3 Lesion Dimensions: 
Previous paragraph 3: 
At Visit 1 and Visit 2 calculate and report the surface area (cm2) of each target lesion by 
multiplying the length of the longest axis in cm and the length of the longest axis 
perpendicular to the first measurement in cm and report to the nearest 1 cm. 
 
Changed paragraph 3 (with typographical error correction highlighted): 
At Visit 1 and Visit 2 calculate and report the surface area (cm2) of each target lesion by 
multiplying the length of the longest axis in cm and the length of the longest axis 
perpendicular to the first measurement in cm and report to the nearest 0.1cm. 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 2 
Page 1 of 8 
Date: 05-NOV-2013                                                                                                                 Supersedes: NEW                    
 
CLINICAL STUDY PROTOCOL 
 
Protocol Number: A-101-SEBK-201 
Amendment Number 2 
 
A RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED, WITHIN SUBJECT 
COMPARISON STUDY OF THE SAFETY, TOLERABILITY AND EFFECTIVENESS 
OF A-101 TOPICAL SOLUTION IN SUBJECTS WITH SEBORRHEIC KERATOSIS  
 
 
 
Sponsor 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Telephone: (484) 324-7933 
Facsimile: (484) 320-2344 
 
Study Contact 
Brian B. Beger 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Telephone: (484) 321-5552 
E-mail: bbeger@aclaristx.com 
 
Medical Monitor 
Stuart D. Shanler, M.D. 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Telephone: (484) 321-5555 
Serious Adverse Event facsimile: (484) 324-2359 
E-mail: sshanler@aclaristx.com 
 
 
 
This document is a privileged and confidential communication of Aclaris Therapeutics, Inc. Acceptance of this 
document constitutes an agreement by the recipient that no unpublished information contained herein will be used, 
published or disclosed without prior written approval from Aclaris Therapeutics, Inc. 
 
 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 2 
Page 2 of 8 
Date: 05-NOV-2013                                                                                                                 Supersedes: NEW                    
 
INVESTIGATOR/SPONSOR AGREEMENT 
 
I have read this protocol amendment and agree to conduct this study in compliance 
with the protocol as amended and with any additional amendments. 
 
 
Investigator Signature: 
 
 
 
 ___________________________________  
 _______________________  
<Investigator Name> 
 
Date 
Investigator 
 
 
 
 
 
 
 
 
 
Sponsor Signature: 
 
 
 
 ___________________________________  
 _______________________  
Christopher Powala 
Date 
Chief Operating Officer 
Aclaris Therapeutics, Inc. 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 2 
Page 3 of 8 
Date: 05-NOV-2013                                                                                                                 Supersedes: NEW                    
 
Table of Contents 
1. 
AMENDMENT HISTORY ............................................................................................................ 4 
2. 
AMENDMENT SUMMARY ......................................................................................................... 4 
3. 
AMENDMENT RATIONALE ...................................................................................................... 4 
4. 
PROTOCOL CHANGES ................................................................................................................ 5 
 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 2 
Page 4 of 8 
Date: 05-NOV-2013                                                                                                                 Supersedes: NEW                    
 
1. 
AMENDMENT HISTORY 
Protocol footer date: 09-SEP-2013 
Previous amendments:  
 Number 1; footer date 24-SEP-2013 
 
 
2. 
AMENDMENT SUMMARY 
The following sections of the A-101-SEBK-201 protocol with footer date 09-SEP-2013, 
approved by Aclaris Therapeutics, Inc. on 09-SEP-2013 are amended: 
 Section 5.3.1 Visit 1 (Day -13 to 0) 
 Section 5.3.2 Visit 2 (Day 1) 
 Section 5.3.4 Visit 5 (Day 22) 
 Section 5.4 Target Lesion Identification 
 Section 5.7.6 Study medication applications 
 Section 6 STUDY ASSESSMENTS 
 Section 6.1.3 Lesion Dimensions  
 Section 6.2.1 Local Skin Reactions (LSR) 
 Section 7.1.1 Adverse Events (AE) 
 Section 8 Pregnancy. 
 
The changes detailed in this amendment and the changes detailed in amendment 1 
(footer date 24-SEP-2013), are incorporated in the attached A-101-SEBK-201 revised 
protocol number 1 dated 14-NOV-2013. 
 
 
3. 
AMENDMENT RATIONALE 
These protocol changes are made to: 
 Respond to recommendations from the Food and Drug Administration; changes 
to sections 5.7.6, 6.2.1, 7.1.1 and 8 
 Allow for enrollment of subjects with smaller seborrheic keratosis lesions 
without affecting the design or scientific rigor of the study; changes in sections 
5.3.1, 5.3.2, 5.4 and 6.1.3   
 Correct study instructions; changes in sections 5.3.4 and 6. 
 
  
 
 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 2 
Page 5 of 8 
Date: 05-NOV-2013                                                                                                                 Supersedes: NEW                    
 
4. 
PROTOCOL CHANGES 
Section 5.3.1 Visit 1 (Day -13 to 0): 
Previous item 13: 
Measure the dimensions of each target lesion; each target lesion must have a surface 
area of ≥1cm2 and ≤4cm2and a thickness that is at least palpable and no greater than 
3mm for the subject to continue in the study (Section 6.1.3). 
 
Changed item 13: 
Measure the dimensions of each target lesion; each target lesion must have a surface 
area of ≥0.5cm2 and ≤4cm2and a thickness that is at least palpable and no greater than 
3mm for the subject to continue in the study (Section 6.1.3). 
 
 
Section 5.3.2 Visit 2 (Day 1): 
Previous item 13: 
Measure the dimensions of each target lesion; each target lesion must have: a surface 
area of ≥1cm2 and ≤4cm2; a thickness that is at least palpable and no greater than 3mm 
for the subject to be randomized (Section 6.1.3). 
 
Changed item 13: 
Measure the dimensions of each target lesion; each target lesion must have: a surface 
area of ≥0.5cm2 and ≤4cm2; a thickness that is at least palpable and no greater than 3mm 
for the subject to be randomized (Section 6.1.3). 
 
 
Section 5.3.4 Visit 5 (Day 22): 
Previous paragraph 4 item 2: 
Schedule Visit 5 for Day 22. 
 
Changed paragraph 4 item 2: 
Schedule Visit 6 for Day 28. 
 
 
Section 5.4 Target Lesion Identification: 
Previous paragraph 4 item 4: 
Have a lesion area of ≥1cm2 and ≤4cm2 (Section 6.1.3). 
 
Changed paragraph 4 item 4: 
Have a lesion area of ≥0.5cm2 and ≤4cm2 (Section 6.1.3) 
 
 
 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 2 
Page 6 of 8 
Date: 05-NOV-2013                                                                                                                 Supersedes: NEW                    
 
Section 5.7.6 Study medication application: 
Previous paragraphs 6: 
At Visit 5 any target lesion that has a PLA grade of >0, and ONLY target lesions that 
have a PLA grade of >0, must receive a retreatment study medication application. 
 
Changed paragraph 6: 
At Visit 5 any target lesion that has a PLA grade of >0, and ONLY target lesions that 
have a PLA grade of >0, must receive a retreatment study medication application 
UNLESS the target lesion: 
 Has a Visit 5 pre-application LSR grade of 3 (severe) for any sign or symptom  
 Is, in the investigator’s opinion, not appropriate for a retreatment study 
medication application. 
 
Add a new paragraph 7 that reads: 
All Visit 5 retreatment applications will be terminated for all subjects if 4 or more 
subjects discontinue from the study due to study medication related AEs. 
 
 
Section 6 STUDY ASSESSMENTS: 
Previous paragraphs 3: 
The following evaluation must be performed with the subject prone with the plane of 
the target lesion horizontal: 
 
Changed paragraph 3: 
The following evaluation may be performed with the subject standing or prone: 
 
 
Section 6.1.3 Lesion Dimensions: 
Previous paragraphs 1: 
The Lesion Dimensions must be measured with the subject prone. 
 
Changed paragraph 4: 
The Lesion Dimensions may be measured with the subject standing or prone. 
 
Previous paragraphs 4: 
The area of each target lesion must be ≥1cm2 and ≤4cm2 at Visit 1 for the subject to be 
enrolled and at Visit 2 for the subject to be randomized. 
 
Changed paragraph 4: 
The area of each target lesion must be ≥0.5cm2 and ≤4cm2 at Visit 1 for the subject to be 
enrolled and at Visit 2 for the subject to be randomized. 
 
 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 2 
Page 7 of 8 
Date: 05-NOV-2013                                                                                                                 Supersedes: NEW                    
 
Section 6.2.1 Local Skin Reactions (LSR): 
Add a new final paragraph that reads: 
The investigator must report any LSR that increases in severity, compared to the Visit 2 
pre-application evaluation, by ≥1 grade AND persists for 2 or more successive visits, as 
an AE (Section 7.1). 
 
Section 7.1.1 Adverse Events (AE): 
Previous paragraph 3: 
Worsening of any of the target lesion assessments should be reported as an AE ONLY if 
the use of the study medication is interrupted or discontinued or if therapy is required 
to manage the event.  
 
Changed paragraph 3: 
Except for Local Skin Reactions (see below) worsening of any of the target lesion 
assessments must be reported as an AE ONLY if the use of the study medication is 
interrupted or discontinued or if therapy is required to manage the event. Any LSR that 
increases in severity, compared to the Visit 2 pre-application evaluation, by ≥1 grade 
AND persists for 2 or more successive visits must be reported as an AE. 
 
 
Section 8 Pregnancy: 
Previous paragraphs 1 and 2: 
WOCBP include any female who has experienced menarche and who has not 
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or 
bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >12 
consecutive months). Even women who are using oral, implanted or injected 
contraceptive hormones (i.e., using a stable dose for ≥ 90 days), an intrauterine device, 
barrier methods (e.g., diaphragm, condoms, spermicides) to prevent pregnancy, 
practicing abstinence or where the partner is sterile (e.g., vasectomy), should be 
considered to be of childbearing potential. 
 
All WOCBP must use an active method of birth control during the course of the study, 
in a manner such that risk of failure is minimized. Abstinence or having a sterile partner 
is not an active method of birth control. 
 
Changed paragraphs 1 and 2: 
WOCBP include any female who has experienced menarche and who has not 
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or 
bilateral oophorectomy) or is not postmenopausal (defined as ≥12 months with no 
menses without an alternative medical cause). Women who are using an active method 
of birth control, are practicing abstinence, or where the partner is sterile (e.g., 
vasectomy), should be considered to be WOCBP.  
 


Protocol number: A-101-SEBK-201                                                                                  Aclaris Therapeutics , Inc. 
Amendment number: 2 
Page 8 of 8 
Date: 05-NOV-2013                                                                                                                 Supersedes: NEW                    
 
All WOCBP must use an effective method of birth control during the course of the 
study, in a manner such that risk of failure is minimized. Effective methods of birth 
control approved for use in this study are: 
 Implants 
 Injectables 
 Patch 
 Combined oral contraceptives 
 ParaGard® or Mirena® intrauterine devices 
 Condom with spermicide; diaphragm with spermicide 
 Vasectomized partner. 
 


Aclaris Therapeutics, Inc. 
Protocol Number: A-101-SEBK-201 
Revised  protocol number: 1 
Page 1 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
CLINICAL STUDY PROTOCOL 
 
Protocol Number: A-101-SEBK-201 
Revised Protocol Number: 1 
Incorporates Amendments Number: 1 & 2 
 
 
A RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED, WITHIN SUBJECT 
COMPARISON STUDY OF THE SAFETY, TOLERABILITY AND EFFECTIVENESS 
OF A-101 TOPICAL SOLUTION IN SUBJECTS WITH SEBORRHEIC KERATOSIS  
 
 
Sponsor 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Telephone: (484) 324-7933 
Facsimile: (484) 320-2344 
 
Study Contact 
Brian B. Beger 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Telephone: (484) 321-5552 
E-mail: bbeger@aclaristx.com 
 
Medical Monitor 
Stuart D. Shanler, M.D. 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Telephone: (484) 321-5555 
Serious Adverse Event facsimile: (484) 324-2359 
E-mail: sshanler@aclaristx.com 
 
 
 
This document is a privileged and confidential communication of Aclaris Therapeutics, Inc. Acceptance of this 
document constitutes an agreement by the recipient that no unpublished information contained herein will be used, 
published or disclosed without prior written approval from Aclaris Therapeutics, Inc. 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 2 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
INVESTIGATOR/SPONSOR AGREEMENT 
 
I have read this protocol and agree to conduct this study in compliance with the 
protocol and any applicable amendments. 
 
 
Investigator Signature: 
 
 
 
____________________________________ 
________________________ 
<Investigator Name> 
 
Date 
Investigator 
 
 
 
 
 
 
 
 
 
Sponsor Signature: 
 
 
 
____________________________________ 
________________________ 
Christopher Powala 
Date 
Chief Operating Officer 
Aclaris Therapeutics, Inc. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 3 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
Table of Contents 
INVESTIGATOR/SPONSOR AGREEMENT ...................................................................................... 2 
1. 
SYNOPSIS ........................................................................................................................................ 6 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ...................................................... 9 
2. 
INTRODUCTION ......................................................................................................................... 11 
2.1. 
Summary ...................................................................................................................................... 11 
2.2. 
Study Rationale ........................................................................................................................... 12 
3. 
STUDY OBJECTIVES .................................................................................................................. 12 
4. 
SELECTION AND DISPOSITION OF STUDY POPULATION ......................................... 13 
4.1. 
Number of Subjects .................................................................................................................... 13 
4.2. 
Study Population Characteristics ............................................................................................ 13 
4.3. 
Inclusion Criteria ........................................................................................................................ 13 
4.4. 
Exclusion Criteria ....................................................................................................................... 13 
4.5. 
Previous and Concomitant Therapies ..................................................................................... 15 
4.5.1. 
Previous therapies .................................................................................................................... 15 
4.5.2. 
Concomitant therapies ............................................................................................................ 15 
4.5.3. 
Prohibited therapies ................................................................................................................ 15 
4.6. 
Subject Discontinuation from the Study ............................................................................... 15 
4.7. 
Subject Number (SN) ................................................................................................................. 16 
4.8. 
Replacement Subjects ................................................................................................................ 16 
5. 
INVESTIGATIONAL PLAN ...................................................................................................... 17 
5.1. 
Study Design ............................................................................................................................... 17 
5.2. 
Study Flow Chart ........................................................................................................................ 18 
5.3. 
Study Visits Description and Procedures .............................................................................. 19 
5.3.1. 
Visit 1 (Day -13 to 0) ................................................................................................................. 19 
5.3.2. 
Visit 2 (Day 1) ........................................................................................................................... 19 
5.3.3. 
Visits 3 and 4 (Days 8 and 15) ................................................................................................ 21 
5.3.4. 
Visit 5 (Day 22) ......................................................................................................................... 22 
5.3.5. 
Visits 6, 7 and 8 (Days 29, 43 and 57) .................................................................................... 23 
5.3.6. 
Visit 9 (Day 78) ......................................................................................................................... 23 
5.4. 
Target Lesion Identification ..................................................................................................... 24 
5.5. 
Subject Instructions ................................................................................................................... 25 
5.6. 
Study Duration ............................................................................................................................ 26 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 4 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
5.7. 
STUDY MEDICATIONS .......................................................................................................... 26 
5.7.1. 
Study medication identity ...................................................................................................... 26 
5.7.2. 
Study medication packaging and labeling .......................................................................... 27 
5.7.3. 
Method of treatment assignment .......................................................................................... 28 
5.7.4. 
Subject randomization ............................................................................................................ 28 
5.7.5. 
Dispensing study medication ................................................................................................ 28 
5.7.6. 
Study medication application ................................................................................................ 28 
5.7.7. 
Dose compliance record .......................................................................................................... 30 
5.7.8. 
Dose modification .................................................................................................................... 30 
5.8. 
Study medication Management ............................................................................................... 31 
5.8.1. 
Accountability .......................................................................................................................... 31 
5.8.2. 
Return and disposition of study supplies ........................................................................... 31 
5.9. 
Other Study Supplies ................................................................................................................ 31 
5.10. 
Blinding ........................................................................................................................................ 31 
5.10.1. 
Verification of blinding .......................................................................................................... 31 
5.10.2. 
Un-blinding during the study medication .......................................................................... 32 
6. 
STUDY ASSESSMENTS ............................................................................................................. 32 
6.1. 
Effectiveness Evaluations ......................................................................................................... 33 
6.1.1. 
Subject’s Self-Assessment (SSA) .......................................................................................... 33 
6.1.2. 
Physician’s Lesion Assessment (PLA) .................................................................................. 34 
6.1.3. 
Lesion Dimensions .................................................................................................................. 35 
6.1.4. 
Signs of Seborrheic Keratosis (SSK) .................................................................................... 35 
6.2. 
Safety Evaluations ...................................................................................................................... 36 
6.2.1. 
Local Skin Reactions (LSR) .................................................................................................... 36 
6.2.2. 
Vital signs .................................................................................................................................. 38 
6.2.3. 
Electrocardiogram (ECG) ........................................................................................................ 39 
6.2.4. 
Clinical laboratory sampling ................................................................................................. 40 
6.2.5. 
Urine pregnancy tests .............................................................................................................. 41 
6.3. 
Other Evaluations ....................................................................................................................... 41 
6.3.1. 
Demographics and medical history ...................................................................................... 41 
6.3.2. 
Standardized photography ..................................................................................................... 41 
7. 
ADVERSE EVENTS ...................................................................................................................... 42 
7.1. 
Definitions ................................................................................................................................... 42 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 5 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
7.1.1. 
Adverse events (AE)................................................................................................................. 42 
7.1.2. 
Serious adverse event (SAE) .................................................................................................. 43 
7.1.3. 
Unexpected adverse event ...................................................................................................... 43 
7.1.4. 
Adverse event reporting period ............................................................................................ 43 
7.1.5. 
Severity ...................................................................................................................................... 44 
7.1.6. 
Relationship to study medication ......................................................................................... 44 
7.2. 
Reporting Procedures ................................................................................................................. 44 
7.2.1. 
Procedures for reporting adverse events ............................................................................. 44 
7.2.2. 
Procedure for reporting a serious adverse event ................................................................ 45 
8. 
PREGNANCY ................................................................................................................................ 46 
9. 
STATISTICAL ANALYSES ........................................................................................................ 47 
9.1. 
Statistical Analysis of Clinical Indices ................................................................................... 47 
9.2. 
Statistical Analysis of Safety Data .......................................................................................... 48 
9.3. 
Sample Size .................................................................................................................................. 48 
10. 
TRAINING, MONITORING, DATA MANAGEMENT AND QUALITY 
ASSURANCE ................................................................................................................................. 49 
10.1. 
Training ........................................................................................................................................ 49 
10.2. 
Monitoring ................................................................................................................................... 49 
10.3. 
Data Management....................................................................................................................... 49 
10.4. 
Quality Assurance ...................................................................................................................... 50 
11. 
ETHICS AND GENERAL STUDY CONDUCT CONSIDERATIONS ............................... 50 
11.1. 
Institutional Review Board (IRB)/Ethics Committee (EC) .................................................. 50 
11.2. 
Ethical Conduct of the Study .................................................................................................... 50 
11.3. 
Subject Information and Consent ........................................................................................... 51 
11.4. 
Study Conduct and Protocol Amendments ........................................................................... 51 
11.5. 
Regulatory Documents .............................................................................................................. 51 
11.6. 
Contractual Requirements ........................................................................................................ 51 
11.7. 
Data Collection and Archiving ................................................................................................ 52 
11.7.1. 
Data collection .......................................................................................................................... 52 
11.7.2. 
Source documentation ............................................................................................................. 52 
11.7.3. 
Archiving ................................................................................................................................... 52 
12. 
SUBJECT INSTRUCTION SHEET ............................................................................................ 53 
 
 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 6 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
1. 
SYNOPSIS 
Title: 
A Randomized, Double-Blind, Vehicle-Controlled, Within Subject Comparison Study of 
the Safety, Tolerability and Effectiveness of A-101 Topical Solution in Subjects with 
Seborrheic Keratosis. 
 
Objectives: 
The main objective of this study is to evaluate the safety and effectiveness of A-101 
(hydrogen peroxide) Solution 25%, 32.5% and 40% when applied to individual 
seborrheic keratosis (SK) target lesions on the back compared with a matching A-101 
Solution Vehicle. 
 
Methodology/Study Design: 
The duration of study participation is anticipated to be a maximum of 95 days per 
subject. This includes the up to 14-day screening period, a visit for a required study 
medication application, a 21-day no treatment period, a visit for an optional study 
medication retreatment application, a 56-day no treatment follow-up period and a 
maximum allowable 4-day Visit 9 visit window. Study visits are: 
 Visit 1 (Day -13 to 0) enrollment; start screening period 
 Visit 2 (Day 1) randomization; study medication application 
 Visit 3 (Day 8) no treatment follow-up 
 Visit 4 (Day 15) no treatment follow-up 
 Visit 5 (Day 22) follow-up visit where target lesions that meets the retreatment 
criteria will receive a second study medication application 
 Visit 6 (Day 29) no treatment follow-up 
 Visit 7 (Day 43) no treatment follow-up 
 Visit 8 (Day 57) no treatment follow-up 
 Visit 9 (Day 78) no treatment follow-up; end of study.  
 
During Visit 1 the investigator will, for each subject, identify 4 individual SK lesions 
(target lesions) on the back for treatment, perform an electrocardiogram (ECG) and 
collect blood samples for clinical laboratory safety tests to determine the subject’s 
eligibility for randomization. Subjects may have more than 4 SK lesions on the back, or 
on other body surfaces, but only the target lesions on the back will be evaluated and 
treated.  
 
During Visit 2, eligible subject’s target lesions will be randomized, each to receive 1 
study medication (a unique study medication for each target lesion) and then the study 
medication applications will be performed. Every eligible subject will receive all 4 of the 
study medications. 
 
At Visits 3 and 4, subjects will be seen for a no treatment follow-up. 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 7 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
 
At Visit 5, subjects will be seen for follow-up and any target lesion that meets the re-
treatment criteria (i.e., Physician’s Lesion Assessment [PLA] >0) will receive a second 
study medication application.  
 
At Visits 6-8, subjects will be seen for a no treatment follow-up. 
 
At Visit 9, subjects will be seen for a no treatment follow-up and discharged from the 
study. 
 
Number of Subjects: 
Approximately 36 subjects will be enrolled in this study at one United States 
investigational center with the goal to have 32 subjects complete the study. 
 
Diagnosis and Main Criteria for Inclusion: 
Subjects will be adult males and females with 4 clinically typical appearing seborrheic 
keratosis target lesions on the back. 
 
Study Medications, Application, and Mode of Administration: 
There are 4 study medications for topical application: 
 A-101 Solution 25% 
 A-101 Solution 32.5% 
 A-101 Solution 40% 
 A-101 Solution Vehicle.  
 
Study medications will be randomly assigned to the 4 target lesions on each subject’s 
back; each subject will have all the 4 study medications applied, 1 study medication to 
each individual target lesion.  
 
There are 16 treatment groups.  Each treatment group consists of one of 8 randomly-
selected permutations for applying each study medication to one of the four target 
lesions per subject.  
 
At Visit 2, eligible subjects will be randomized to one of the treatment groups 
(determining the study medication that will be applied to each individual target lesion) 
in a blinded manner. After randomization an investigational center staff member other 
than the investigator, will perform, the study medication applications. 
 
At Visit 5, any lesion that meets the retreatment criteria (i.e., PLA >0) will receive a 
second study medication application.  
  


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 8 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
Duration of Treatment: 
The planned treatment and study duration are: 
 Enrollment period: approximately 35 days 
 Subject participation period: up to 95 days 
 Study duration (first subject first visit through last subject last visit): 
approximately 130 days.   
 
Evaluations – Effectiveness: 
The investigator will evaluate the average overall severity of each SK target lesion using 
the Physician’s Lesion Assessment (PLA) and the subject will evaluate each target lesion 
using the Subject’s Self-Assessment (SSA). The investigator will measure Lesion 
Dimensions (i.e., surface area and thickness) throughout the study for each target lesion. 
 
Evaluations – Safety: 
Local Skin Reactions (LSR) for each target lesion, clinical laboratory safety tests, ECGs, 
vital sign readings, concomitant therapies, urine pregnancy tests and adverse events 
(AEs) will be monitored throughout the study. 
 
Evaluations – Other: 
The investigator will evaluate Signs of Seborrheic Keratosis (SSK) throughout the study 
and take standardized color photographs to document the status of the target lesions 
throughout the study. 
 
Statistical Methods: 
The primary effectiveness analyses will be comparisons between Vehicle and each 
active treatment, based on mean change from the Visit 2 PLA, using a repeated-
measures Analysis of Covariance model suitable for the study design. For this purpose, 
the primary analysis visit will be Visit 9. Secondary effectiveness analyses will include a 
similar analysis of SSA and other effectiveness evaluations suitable for analysis as 
continuous variables. In addition, secondary analyses will be performed on proportion 
of PLA and SSA responders, where a subject will be considered a responder if the Visit 
9 score is 0.  A similar responder analysis will be done at Visit 5. Chi-square will be used 
to analyze difference in response rates. 
 
  


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 9 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Term 
AE  
Adverse Event 
°C 
Degrees Centigrade 
cm 
Centimeters 
CR 
 
Clinically Relevant 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
e.g.  
for example (Latin; exempla gratia) 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
°F 
Degrees Fahrenheit 
FDA 
Food and Drug Administration 
g 
Gram 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization  
i.e.  
that is (Latin; id est) 
IPL 
Intense Pulsed Laser 
IRB 
Institutional Review Board 
ITT 
Intent To Treat 
LSR 
Local Skin Reactions 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
Milliliter 
NCR 
Not Clinically Relevant 
OTC 
Over-The-Counter 
PDT 
Photodynamic Therapy 
PLA 
Physician’s Lesion Assessment 
PP 
Per Protocol 
SAE 
Serious Adverse Event 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 10 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
Abbreviation 
Term 
SK 
Seborrheic Keratosis 
SN 
Subject Number 
SOP 
Standard Operation Procedure 
SSA 
Subject’s Self-Assessment 
SSK 
Signs of Seborrheic Keratosis 
US 
United States 
WOCBP 
Women of childbearing potential 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 11 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
2. 
INTRODUCTION 
2.1. 
Summary 
Seborrheic keratosis (SK) is one of the most common skin tumors in man. These benign 
epithelial skin tumors are most commonly seen in older individuals, increasing in 
prevalence with increasing age, and affect men and women roughly equally. While the 
growths may be solitary, they often occur in large numbers and typically present as 
well demarcated, elevated or “stuck-on” appearing papules or plaques that may vary 
from flesh-colored, to shades of yellow, gray, brown, or black.  
 
Though benign, they 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 achieve cure rates, many 
require specialized training and the use of expensive equipment, they are painful and 
may require anesthesia and/or analgesia, and they are often complicated by significant 
adverse cosmetic 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. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 12 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
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, 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 and in high concentrations; it is 
used in bleaching vegetables, 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.  
 
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 preliminary clinical trial suggested that the topical application of H2O2 35% 
solution to SK lesions has the potential to safely and effectively resolve the SK lesions 
without the need for analgesia and/or anesthesia, and with a minimal risk of transient 
or permanent hypopigmentation, hyperpigmentation, or scarring. 
 
2.2. 
Study Rationale 
Preliminary clinical information, as discussed above, suggests that H2O2 35% solution 
applied topically may resolve SK lesions. This study is designed to provide initial 
safety, tolerability and effectiveness data for A-101 (H2O2) Solution when applied to 
target lesions of SK.  
 
3. 
STUDY OBJECTIVES 
The main objective of this study is to evaluate the effectiveness of A-101 Solution 25%, 
32.5% and 40% when applied to SK target lesions on the back compared with a 
matching A-101 Solution Vehicle. Secondary objectives include evaluating the safety 
and tolerability of A-101 Solution when applied topically in subjects with SK. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 13 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
4. 
SELECTION AND DISPOSITION OF STUDY POPULATION 
4.1. 
Number of Subjects 
Approximately 36 subjects will be enrolled in this study at one United States (US) 
investigational center with the goal to have 32 subjects complete the study. 
 
4.2. 
Study Population Characteristics 
Male and female subjects, 18 years of age or older, with a diagnosis of SK and at least 4 
clinically typical SK target lesions on the back, who meet all the inclusion criteria and 
none of the exclusion criteria will be eligible to enroll in this study. 
 
4.3. 
Inclusion Criteria 
In order to be eligible for the study, subjects must fulfill all of the following criteria: 
1. 
Is at least 18 years of age 
2. 
Has a clinical diagnosis of stable clinically typical seborrheic keratosis 
3. 
Has at least 4 appropriate seborrheic keratosis target lesions on the back 
4. 
If subject is a women of childbearing potential, she must have a negative 
urine pregnancy test and must agree to use an active form of birth control 
for the duration of the study 
5. 
Is non-pregnant and non-lactating 
6. 
Is in good general health and free of any disease state or physical 
condition which, in the investigator’s opinion, might impair evaluation of 
any target lesion or which exposes the subject to an unacceptable risk by 
study participation 
7. 
Is willing and able to follow all study instructions and to attend all study 
visits 
8. 
Is able to comprehend and willing to sign an Informed Consent Form 
(ICF). 
 
4.4. 
Exclusion Criteria 
Any subject who meets one or more of the following criteria will not be included in this 
study:  
1. 
Has clinically atypical and/or rapidly growing seborrheic keratosis 
lesions 
2. 
Has presence of multiple eruptive seborrheic keratosis lesions (Sign of 
Lesser-Trelat) 
 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 14 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
3. 
Has used any of the following systemic therapies within the specified period 
prior to Visit 1: 
 Retinoids; 180 days 
 Glucocortico-steroids; 28 days 
 Anti-metabolites (e.g., methotrexate); 28 days 
4. 
Has used any of the following topical therapies on the treatment area within 
the specified period prior to Visit 1: 
 Retinoids; 90 days 
 Liquid nitrogen, electrodesiccation, curettage, imiquimod, 5-
flurouracil, or ingenol mebutate; 60 days 
 Glucocortico-steroids or antibiotics; 14 days 
 Moisturizers/emollients, sunscreens; 12 hours 
5. 
Has had any LASER, light (e.g., intense pulsed light [IPL], photo-dynamic 
therapy [PDT]) or other energy based therapy on the treatment area within 
180 days prior to Visit 1 
6. 
Has a history of keloid formation or hypertrophic scarring 
7. 
Has a current systemic malignancy 
8. 
Has a history of, within the 180 days prior to Visit 1, or has a current 
cutaneous malignancy  on the treatment area 
9. 
Has a current pre-malignancy (e.g., actinic keratosis) on the treatment area 
10. 
Has had body art (e.g., tattoos, piercing, sculpting, etc.) or any other 
invasive, non-therapeutic procedure performed on the treatment area that, 
in the opinion of the investigator, might put the subject at undue risk or 
interfere with the study conduct or evaluations  
11. 
Has excessive tan on the treatment area that, in the opinion of the 
investigator, might put the subject at undue risk or interfere with the 
study conduct or evaluations  
12. 
Has experienced a sunburn on the treatment area within the previous 4 
weeks 
13. 
Has a history of sensitivity to any of the ingredients in the study 
medications 
14. 
Has any current skin disease (e.g., psoriasis, atopic dermatitis,  eczema, 
sun damage, etc.), or condition (e.g., sunburn, tattoos, excessive hair, open 
wounds on the back) that, in the opinion of the investigator, might put the 
subject at undue risk or interfere with the study conduct or evaluations 
15. 
Has participated in an investigational drug trial in which administration 
of an investigational study medication occurred within 30 days prior to 
Visit 1. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
4.5. 
Previous and Concomitant Therapies 
4.5.1. 
Previous therapies 
During Visit 1, subjects will be questioned to ensure they have not used any excluded 
therapies (Section 4.4). 
 
4.5.2. 
Concomitant therapies 
Concomitant therapies are any new or existing therapy received from Visit 1 until 
discharge from the study.  
 
Concomitant therapies include drug (e.g., prescription, over-the-counter [OTC]) and 
non-drug (e.g., chiropractic, physical therapy, energy-based treatments) therapies. 
Subjects will refrain from receipt of any therapy in compliance with the 
inclusion/exclusion criteria. Subjects should refrain from changing the use of any 
concomitant therapies during the study.  
 
All new or modified concomitant therapies used during the study must be recorded. 
 
Any new or modified concomitant therapy must be considered to determine if it is 
related to an AE. An AE must be reported unless the therapy is modified for non-
medical reasons (e.g., health insurance purposes) or it is for prophylaxis (e.g., 
vaccinations). 
 
Subjects must avoid applying any topical product to the target lesions within 12 hours 
prior to any study visit, and for at least 6 hours after any study medication application. 
 
4.5.3. 
Prohibited therapies 
During the course of this study, subjects are prohibited from using therapies listed in 
the exclusion criteria (Section 4.4). The investigator should notify the Aclaris 
Therapeutics, Inc. Medical Monitor (Section 7.2) immediately if any prohibited therapies 
are required to ensure subject safety. 
 
4.6. 
Subject Discontinuation from the Study 
Subjects will be informed that they are free to withdraw from the study at any time and 
for any reason.  
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 16 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
The investigator may remove a subject from the study if, in the investigator's opinion, it 
is not in the best interest of the subject to continue the study. Examples of other reasons 
subjects may be discontinued from the study are a change in compliance with an 
inclusion or exclusion criterion, occurrence of AEs, occurrence of pregnancy or use of a 
prohibited therapy. Notification of discontinuation will immediately (within 24 hours) 
be made to the Aclaris Therapeutics, Inc. study monitor.  
 
In case of premature discontinuation of study participation, efforts will be made to 
perform all final study day assessments. The date the subject is withdrawn from the 
study and the reason for discontinuation will be recorded on the subject’s case report 
forms (CRFs). All withdrawn subjects with ongoing AEs will be followed as appropriate 
(Section 7.2.1). 
 
The study may be discontinued at the discretion of the investigator or 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. 
 
4.7. 
Subject Number (SN) 
The investigator or designee will assign a unique subject number (SN) to each subject at 
Visit 1.  
 
The SN format will be 2 digits and must be assigned in ascending numerical order, 
without omitting or repeating any number, starting with 01. For example, the SN for the 
fifth subject enrolled in the study will be 05.  
 
The subject will be identified using the SN in all study documentation for the duration 
of the study. 
 
4.8. 
Replacement Subjects 
Subject enrollment will continue until approximately 36 subjects have been 
randomized. Subjects who are randomized and do not complete the study will not be 
replaced. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 17 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
5. 
INVESTIGATIONAL PLAN 
5.1. 
Study Design 
This is a randomized, double-blind, vehicle-controlled, within subject comparison study 
of A-101 Solution 25%, 32.5% and 40% and the A-101 Solution Vehicle to investigate the 
safety, tolerability and effectiveness in subjects with SK. Eligible subjects will have 4 
appropriate SK target lesions on the back.  
 
The duration of study participation is anticipated to be a maximum of 95 days per 
subject. This includes the up to 14-day screening period, a visit for a required study 
medication application, a 21-day no treatment period, a visit for an optional study 
medication retreatment application, a 56-day no treatment follow-up period and a 
maximum allowable 4-day Visit 9 visit window. Study visits are: 
 Visit 1 (Day -13 to 0) enrollment; screening period 
 Visit 2 (Day 1) randomization; study medication application 
 Visit 3 (Day 8) no treatment follow-up 
 Visit 4 (Day 15) no treatment follow-up 
 Visit 5 (Day 22) follow-up visit where any target lesion that meets the 
retreatment criteria will receive a second study medication application 
 Visit 6 (Day 29) no treatment follow-up 
 Visit 7 (Day 43) no treatment follow-up 
 Visit 8 (Day 57) no treatment follow-up 
 Visit 9 (Day 78) no treatment follow-up; end of study.  
 
During Visit 1 the investigator will, for each subject, identify 4 seborrheic keratosis 
lesions (target lesions) on the back for treatment, perform an electrocardiogram (ECG) 
and collect blood samples for clinical laboratory safety tests to determine the subject’s 
eligibility for randomization. Subjects may have more than 4 lesions on the back, or on 
other body surfaces, but only the target lesions on the back will be evaluated and 
treated.  
 
During Visit 2, eligible subjects will be randomized to study medication (a unique study 
medication for each target lesion) and then the study medication applications will be 
performed.  
 
At Visits 3 and 4, subjects will be seen for a no treatment follow-up. 
 
At Visit 5, subjects will be seen for follow-up and any lesion that meets the re-treatment 
criteria (Section 5.7.6) will receive a second application of the assigned study 
medication.  
 
At Visits 6-8, subjects will be seen for a no treatment follow-up. 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 18 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
 
At Visit 9, subjects will be seen for a no treatment follow-up and discharged from the 
study. 
 
The study will be conducted at one US investigational center. 
 
5.2. 
Study Flow Chart 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Protocol 
Section 
Day 
-13 to 0 
1 
8 15 
22 
29 43 57 78 
Informed consent 
X 
 
 
 
 
 
 
 
 
11.3 
Subject number 
X 
 
 
 
 
 
 
 
 
4.7 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
4.3/4.4 
Demographics & medical 
history 
X 
 
 
 
 
 
 
 
 
6.3.1 
Vital signs 
X 
X 
 
 
 
 
 
 
X 
6.2.2 
Clinical laboratory 
sampling 
X 
X 
 
 
 
 
 
 
X 
6.2.4 
Electrocardiogram 
X 
X 
 
 
 
 
 
 
X 
6.2.3 
Urine pregnancy tests 
X 
X 
 
 
 
 
 
 
X 
6.2.5 
Target lesion identification 
X 
 
 
 
 
 
 
 
 
5.4 
Subject’s self-assessment 
 
X1 X 
X 
X1 
X 
X 
X 
X 
6.1.1 
Physician’s lesion 
assessment 
X 
X1 X 
X 
X1 
X 
X 
X 
X 
6.1.2 
Signs of seborrheic 
keratosis 
 
X1 X 
X 
X1 
X 
X 
X 
X 
6.1.4 
Lesion dimensions 
X 
X1 X 
X 
X1 
X 
X 
X 
X 
6.1.3 
Local skin reactions 
 
X2 X 
X 
X2 
X 
X 
X 
X 
6.2.1 
Standardized photography 
X 
X1 X 
X 
X1 
X 
X 
X 
X 
6.3.2 
Subject randomization 
 
X 
 
 
 
 
 
 
 
5.7.4 
Study medication 
application 
 
X 
 
 
X3 
 
 
 
 
5.7.6 
Subject instructions 
X 
X 
X 
X 
X 
X 
X 
X 
X 
5.5 
Concomitant therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
4.5.2 
Adverse events 
 
X2 X 
X 
X2 
X 
X 
X 
X 
7 
1 Performed prior to the study medication application 
2 Performed prior to and after completion of all study medication applications 
3 Only for Target Lesions that meet the retreatment criteria 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
5.3. 
Study Visits Description and Procedures 
A written, signed informed consent form (ICF) must be obtained from each subject prior 
to performing any study related procedures and/or evaluations. 
 
5.3.1. 
Visit 1 (Day -13 to 0)  
At this visit, the investigator or designee will: 
1. Review and explain the nature of the study to the subject, obtain the subject’s 
signature on the appropriate approved ICF and Health Insurance Portability and 
Accountability Act (HIPAA) authorization and provide a signed and dated copy 
to the subject (Section 11.3) 
2. Assign a SN to the subject (Section 4.7) 
3. Confirm the subject meets all inclusion criteria and no exclusion criteria (Section 
4.3 and 4.4 respectively) 
4. Collect demographic and medical history information (Section 6.3.1) 
5. Collect concomitant therapies information (Section 4.5.2) 
6. Measure vital signs (Section 6.2.2) 
7. Collect blood samples for clinical laboratory tests (Section 6.2.4) 
8. Perform a urine pregnancy test for women of childbearing potential (WOCBP); 
results must be negative for the subject to continue in the study (Section 6.2.5) 
9. Perform ECG (Section 6.2.3) 
10. Identify 4 appropriate seborrheic keratosis target lesions on the subject’s back 
(Section 5.4) 
11. Take standardized color photographs of the target lesions (Section 6.3.2) 
12. Perform a PLA for each target lesion; a PLA grade of ≥2 is required for each 
target lesion for the subject to continue in the study (Section 6.1.2) 
13. Measure the dimensions of each target lesion; each target lesion must have a 
surface area of ≥0.5cm2 and ≤4cm2and a thickness that is at least palpable and no 
greater than 3mm for the subject to continue in the study (Section 6.1.3) 
14. Review the study instructions with the subject and dispense a Subject Instruction 
Sheet (Section 5.5) 
15. Schedule Visit 2 within 14 days. 
 
5.3.2. 
Visit 2 (Day 1)  
This visit must occur within 14 days after Visit 1. 
 
Subsequent study visit dates must be scheduled based on the date of this visit. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
This visit may not occur before the investigator reviews the Visit 1 clinical laboratory 
test and ECG results. For the subject to continue in the study all clinical laboratory test 
results must be within the range of normal for the laboratory or, if there are any 
abnormal results, they must be defined as not clinically relevant (NCR) by the 
investigator (Section 6.2.4). In addition, ECG results must be defined as normal for the 
subject to continue (Section 6.2.3).  
 
At this visit, the investigator or designee will perform the following procedures PRIOR 
TO RANDOMIZATION: 
1. Query the subject in a non-directive manner about any changes in her/his health 
since the previous visit and report all AEs on the appropriate form (Section 7.2.1) 
2. Query the subject about any changes in her/his concomitant therapies since the 
previous visit and report changes on the appropriate form (Section 4.5.2) 
3. Confirm the subject continues to comply with all study restrictions and has 
followed all study instructions (Section 5.5) 
4. Measure vital signs (Section 6.2.2) 
5. Collect blood samples for clinical laboratory tests (Section 6.2.4) 
6. Perform a urine pregnancy test for WOCBP; results must be negative for the 
subject to be randomized (Section 6.2.5) 
7. Perform ECG (Section 6.2.3) 
8. Confirm the location of the 4 target lesions (Section 5.4) 
9. Take standardized color photographs of the target lesions (Section 6.3.2) 
10. Have the subject perform an SSA for each target lesion (Section 6.1.1) 
11. ONLY AFTER THE SUBJECT COMPLETES THE SSA perform a PLA for each 
target lesion; a PLA grade of ≥2 is required for each target lesion for the subject to 
be randomized (Section 6.1.2) 
12. Perform an SSK for each target lesion (Section 6.1.4) 
13. Measure the dimensions of each target lesion; each target lesion must have: a 
surface area of ≥0.51cm2 and ≤4cm2; a thickness that is at least palpable and no 
greater than 3mm for the subject to be randomized (Section 6.1.3) 
14. Have the subject perform a pre-application Local Skin Reaction assessment of the 
symptoms for each target lesion (Section 6.2.1) 
15. Perform a pre-application Local Skin Reaction assessment of the signs for each 
target lesion (Section 6.2.1) 
16. Confirm subject is eligible for randomization, discharge from the study subjects 
who are not eligible for randomization (Section 4.6). 
 
 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
For subjects eligible for randomization the investigator or designee will perform the 
following procedures:  
1. Randomize eligible subjects (Section 5.7.4) 
2. An investigational center staff member, other than the investigator, will perform 
the initial study medication application for all 4 target lesions (Section 5.7.6) 
3. Have the subject perform a post-application Local Skin Reaction assessment of 
the symptoms for each target lesion 10 (±4) minutes after the study medication 
application to all target lesions is completed (Section 6.2.1) 
4. Perform a post-application Local Skin Reaction assessment of the signs for each 
target lesion 20 (±4) minutes after the study medication application to all target 
lesions is completed (Section 6.2.1) 
5. Monitor the subject for at least 20 minutes after completion of the study 
medication applications to detect any adverse events (Section 7.2.1) 
6. Review the study instructions and restrictions with the subject (Section 5.5) 
7. Schedule Visit 3 for Day 8. 
 
5.3.3. 
Visits 3 and 4 (Days 8 and 15) 
These visits must occur within the following visit window after Visit 2: 
 Visit 3, 7 days (±4 days) 
 Visit 4, 14 days (±4 days) 
 
At these visits, the investigator or designee will perform the following procedures: 
1. Query the subject in a non-directive manner about any changes in her/his health 
since the previous visit and report all AEs on the appropriate form (Section 7.2.1) 
2. Query the subject about any changes in her/his concomitant therapies since the 
previous visit and report changes on the appropriate form (Section 4.5.2) 
3. Confirm the subject continues to comply with all study restrictions and has 
followed all study instructions (Section 5.5) 
4. Confirm the location of the 4 target lesions (Section 5.4) 
5. Take standardized color photographs of the target lesions (Section 6.3.2) 
6. Have the subject perform an SSA for each target lesion (Section 6.1.1) 
7. ONLY AFTER THE SUBJECT COMPLETES THE SSA perform a PLA for each 
target lesion (Section 6.1.2) 
8. Perform an SSK for each target lesion (Section 6.1.4) 
9. Measure the dimensions of each target lesion (Section 6.1.3) 
10. Have the subject perform a Local Skin Reaction assessment of the symptoms for 
each target lesion (Section 6.2.1) 
11. Perform a Local Skin Reaction assessment of the signs for each target lesion 
(Section 6.2.1) 
12. Review the study instructions and restrictions with the subject (Section 5.5) 
13. Schedule the next study visit. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
5.3.4. 
Visit 5 (Day 22)  
This visit must occur 21 days (±4 days) after Visit 2. 
 
At this visit, the investigator or designee will perform the following procedures PRIOR 
TO ANY RETREATMENT STUDY MEDICATION APPLICATION: 
1. Query the subject in a non-directive manner about any changes in her/his health 
since the previous visit and report all AEs on the appropriate form (Section 7.2.1) 
2. Query the subject about any changes in her/his concomitant therapies since the 
previous visit and report changes on the appropriate form (Section 4.5.2) 
3. Confirm the subject continues to comply with all study restrictions and has 
followed all study instructions (Section 5.5) 
4. Confirm the location of the 4 target lesions (Section 5.4) 
5. Take standardized color photographs of the target lesions (Section 6.3.2) 
6. Have the subject perform an SSA for each target lesion (Section 6.1.1) 
7. ONLY AFTER THE SUBJECT COMPLETES THE SSA perform a PLA for each 
target lesion (Section 6.1.2) 
8. Perform an SSK for each target lesion (Section 6.1.4) 
9. Measure the dimensions of each target lesion (Section 6.1.3) 
10. Have the subject perform a Local Skin Reaction assessment of the symptoms for 
each target lesion (Section 6.2.1) 
11. Perform a Local Skin Reaction assessment of the signs for each target lesion 
(Section 6.2.1) 
12. Identify target lesions, if any, that require a retreatment study medication 
application (i.e., target lesion has a PLA grade >0; Section 5.7.6) 
 
ONLY for subjects that require a retreatment study medication application, the 
investigator or designee will perform the following procedures:  
1. An investigational center staff member, other than the investigator, will perform 
a retreatment study medication application for the appropriate target lesion(s) 
(Section 5.7.6) 
2. Have the subject perform a post-application Local Skin Reaction assessment of 
the symptoms for each target lesion that was retreated 10 (±4) minutes after the 
study medication application(s) is(are) completed (Section 6.2.1) 
3. Perform a post-application Local Skin Reaction assessment of the signs for each 
target lesion that was retreated 20 (±4) minutes after the study medication 
application(s) is(are) completed (Section 6.2.1) 
4. Monitor the subject for at least 20 minutes after completion of all retreatment 
study medication applications to detect any adverse events (Section 7.2.1) 
 
For all subjects the investigator or designee will perform the following procedures: 
1. Review the study instructions and restrictions with the subject (Section 5.5) 
2. Schedule Visit 6 for Day 28. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
5.3.5. 
Visits 6, 7 and 8 (Days 29, 43 and 57) 
These visits must occur within the following visit window after Visit 2: 
 Visit 6, 28 days (±4 days) 
 Visit 7, 42 days (±4 days) 
 Visit 8, 56 days (±4 days). 
 
At these visits, the investigator or designee will perform the following procedures: 
1. Query the subject in a non-directive manner about any changes in her/his health 
since the previous visit and report all AEs on the appropriate form (Section 7.2.1) 
2. Query the subject about any changes in her/his concomitant therapies since the 
previous visit and report changes on the appropriate form (Section 4.5.2) 
3. Confirm the subject continues to comply with all study restrictions and has 
followed all study instructions (Section 5.5) 
4. Confirm the location of the 4 target lesions (Section 5.4) 
5. Take standardized color photographs of the target lesions (Section 6.3.2) 
6. Have the subject perform an SSA for each target lesion (Section 6.1.1) 
7. ONLY AFTER THE SUBJECT COMPLETES THE SSA perform a PLA for each 
target lesion (Section 6.1.2) 
8. Perform an SSK for each target lesion (Section 6.1.4) 
9. Measure the dimensions of each target lesion (Section 6.1.3) 
10. Have the subject perform a Local Skin Reaction assessment of the symptoms for 
each target lesion (Section 6.2.1) 
11. Perform a Local Skin Reaction assessment of the signs for each target lesion 
(Section 6.2.1) 
12. Review the study instructions and restrictions with the subject (Section 5.5) 
13. Schedule the next study visit as appropriate. 
 
5.3.6. 
Visit 9 (Day 78) 
This visit must occur 77 days (±4 days) after Visit 2. 
 
At this visit, the investigator or designee will perform the following procedures: 
1. Query the subject in a non-directive manner about any changes in her/his health 
since the previous visit and report all AEs on the appropriate form (Section 7.2.1) 
2. Query the subject about any changes in her/his concomitant therapies since the 
previous visit and report changes on the appropriate form (Section 4.5.2) 
3. Confirm the subject continues to comply with all study restrictions and has 
followed all study instructions (Section 5.5) 
4. Measure vital signs (Section 6.2.2) 
5. Collect blood samples for clinical laboratory tests (Section 6.2.4) 
6. Perform a urine pregnancy test for WOCBP (Section 6.2.5) 
7. Perform ECG (Section 6.2.3) 
8. Confirm the location of the 4 target lesions (Section 5.4) 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
9. Take standardized color photographs of the target lesions (Section 6.3.2) 
10. Have the subject perform an SSA for each target lesion (Section 6.1.1) 
11. ONLY AFTER THE SUBJECT COMPLETES THE SSA perform a PLA for each 
target lesion (Section 6.1.2) 
12. Perform an SSK for each target lesion (Section 6.1.4) 
13. Measure the dimensions of each target lesion (Section 6.1.3) 
14. Have the subject perform a Local Skin Reaction assessment of the symptoms for 
each target lesion (Section 6.2.1) 
15. Perform a Local Skin Reaction assessment of the signs for each target lesion 
(Section 6.2.1) 
16. Discharge the subject from the study. 
 
5.4. 
Target Lesion Identification 
At Visit 1, the investigator will identify 4 target lesions on the treatment area on each 
subject’s back for treatment and evaluation.  
 
For this study, the treatment area on the back is defined vertically from above the 
beltline to below the neck and horizontally from the left posterior axillary line to the 
right posterior axillary line.  
 
Have the subject lie prone with the plane of the target lesions horizontal, except for the 
PLA, which must be performed with the subject standing (Section 6.1.2).  
 
Each target lesion must: 
 Have a clinically typical appearance  
 Be treatment naïve 
 Have a PLA of ≥2 (Section 6.1.2) 
 Have a lesion area of ≥0.5cm2 and ≤4cm2 (Section 6.1.3)  
 Have a thickness above the normal surrounding skin that is at 
least palpable and not greater than 3mm (Section 6.1.3) 
 Be a discrete lesion 
 Be separated from other target lesions, and from any 
confounding physical characteristic by at least 3cm 
 Be able to be photographed  
 Not be in an intertriginous fold 
 Not be in an area where clothing, such as a bra, might cause 
physical irritation 
 Not be pedunculated. 
 
Number the target lesions 1-4. Place the appropriate identification sticker (provided) for 
each individual target lesion so it will be visible in the photographs.  
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
Take a series of photographs as described in the photography instructions.  
 
Detailed instructions for taking the study photographs will be provided to the site prior 
to the initiation of subject enrollment. 
 
At Visits 2-9 use the photographs created at Visit 1 to confirm the location of the target 
lesions. 
 
5.5. 
Subject Instructions 
An investigational center staff member will dispense a Subject Instruction Sheet to each 
subject at Visit 1 (Section 12). 
 
Throughout the study, the subjects should: 
 Continue their routine cleansing regimen except they should avoid vigorous 
scrubbing of the back (e.g., loofah, back brushes, scrubbing straps, abrasive 
cleansing pads, etc.) 
 Continue their routine cosmetics and skin care products 
 Not apply any topical products to the target lesions (except sunscreens as 
described below) 
 Avoid exposing their back to excessive natural or artificial ultraviolet radiation 
(e.g., sunlight, tanning beds) and use sunscreen on the back, including on the 
target lesions, if excessive exposure cannot be avoided 
 Avoid or modify activities (e.g., vigorous exercise, carrying heavy backpacks, 
back massages, etc.) and clothing (e.g., irritating bras, compression clothing, etc.) 
that might irritate the target lesions 
 Bring the subject instruction sheet with them to each visit. 
 
On study visit days, the subjects should: 
 Wear a loose fitting blouse/shirt to the visit (Note: clothing that comes in contact 
with the study medication may be bleached) 
 Not apply any topical products to their back within 12 hours prior to the visit 
(Note: routine cleansing products are allowed) 
 After the completion of any study visit where a study medication application 
was performed do not: 
o Apply any topical products to the back for at least 6 hours 
o Wash/submerge the target lesions for at least 6 hours. 
 
Contact the study staff immediately if you have any study related questions. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
5.6. 
Study Duration 
The duration of study participation is anticipated to be a maximum of 95 days per 
subject. This includes the up to 14-day screening period, a visit for a required study 
medication application, a 21-day no treatment period, a visit for an optional study 
medication retreatment application, a 56-day no treatment follow-up period and a 
maximum allowable 4-day Visit 9 visit window.   
 
The total study duration is anticipated to be approximately 130 days from the first 
subject’s first visit to the last subject’s last visit.   
 
The study end date is the date of the last subject’s last visit.  
 
5.7. 
STUDY MEDICATIONS 
5.7.1. 
Study medication identity 
The study medications are water-clear, colorless solutions that are indistinguishable in 
physical appearance. The study medications must be stored in a secure area with 
limited access under appropriately controlled and monitored storage conditions. 
 
Study Medication Information 
Study medication 
name 
A-101 Solution 
40% 
A-101 Solution 
32.5% 
A-101 Solution 
25% 
A-101 Solution 
Vehicle 
Manufacturer 
Pharmaceutical Manufacturing and Research Services, Horsham, PA, US 
A-101 concentration 
(%) 
40 
32.5 
25 
0 
Pharmaceutical 
Form 
Solution 
Storage Conditions 
68°F to 77°F (20°C to 25°C) protected from light, excessive heat, open 
flame and combustibles, out of direct sunlight and in a well-ventilated, 
dry area 
Dose regimen 
 
Route 
Topical 
Frequency 
1 application to each target lesion at Visit 2 with a possible retreatment 
application at Visit 5 
Duration of 
administration 
Up to 2 applications to each target lesion 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 27 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
5.7.2. 
Study medication packaging and labeling 
The study medications will be packaged in identical appearing, single-use, 2-dram 
(~7.4mL) amber glass, screw-top vials that each contains approximately 3mL of study 
medication. 
 
One Subject Kit that contains 3 vials of each of the 4 study medications (12 vials total) 
will be provided to the investigational center for each subject. Subject Kits will be 
labeled with a two-part, three-panel, double-blind label. One part (one-panel) of the 
label remains attached to the Subject Kit, the other part (two-panel tear-off) is separated 
and attached to the subject’s Label Page CRF when the study medication is first 
dispensed for a subject. 
 
The affixed part and the first panel of the tear-off part of the Subject Kit label show at 
least the following: 
 Subject Kit number (randomization number) 
 Protocol number 
 Storage conditions 
 Sponsor information 
 Investigational drug warning 
 Space to enter SN 
 Space to enter the subject’s initials 
 Space to enter the date randomized. 
 
The second panel of the tear-off part is a blinded label (e.g., sealed, tamper-evident 
envelope, a scratch-off panel or equivalent) which when opened identifies the contents 
of the vials. The blinded label should only be opened in a medical emergency (Section 
5.10.2). 
 
Each study medication vial will be labeled with a one-part label that shows at least the 
following: 
 Subject Kit number (randomization number) 
 Protocol number 
 Target lesion number 
 Vial number 
 Investigational drug warning 
 Space to enter SN 
 Space to enter date of application. 
 
 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 28 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
5.7.3. 
Method of treatment assignment 
Prior to the start of the study, Aclaris Therapeutics, Inc. or a designated third party will 
generate a list of randomization numbers that shall be transmitted to the assigned 
clinical packaging organization for study medication labeling. 
The randomization list will be stored with access limited to designated personnel for 
study medication labeling. The randomization list will be made available as appropriate 
to un-blind the database. 
 
5.7.4. 
Subject randomization 
At Visit 2, an investigational center staff member other than the investigator will assign 
study medication to eligible subjects by selecting Subject Kits in chronological sequence 
and in ascending numerical order starting with the lowest available Subject Kit number 
(the Subject Kit number is the randomization number). No Subject Kit number will be 
omitted or reused. 
 
The sequence of study medications assignment will be randomly assigned. 
 
The investigational center staff member randomizing the subject will enter the SN, 
subject initials and date randomized on both parts of the Subject Kit label, remove the 
tear-off part, attach it to the subject’s Label Page CRF and record the Subject Kit number 
in the subject’s CRF.  
 
5.7.5. 
Dispensing study medication 
The study medications must be applied only to study subjects, only at the 
investigational center and only by authorized personnel as required by applicable 
regulations and guidelines. 
 
At Visit 2, after a subject is randomized (Section 5.7.4), locate the appropriate Subject Kit 
and the unused study medication vial with the lowest vial number labeled with each 
target lesion number. Enter the SN and date of application on each vial label. 
 
At Visit 5, perform application(s) for any target lesion that requires a retreatment 
(Section 5.7.6). Locate the appropriate Subject Kit and the unused study medication vial 
with the lowest number labeled for the appropriate target lesion number(s). Use a 
different vial from the vial used for the Visit 2 application. Enter the SN and date of 
application on each vial label. 
 
5.7.6. 
Study medication application 
The study medications are for external, topical use on the target lesions on the 
appropriate study subject only.  


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 29 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
 
An investigational center staff member other than the investigator will perform all 
study medication applications. The staff member must comply with the study 
medication handling warnings (Section 5.7.1) 
 
At Visit 2, the staff member will perform an initial study medication application for 
each target lesion (4 target lesions).  
 
To perform a study medication application for a target lesion the investigational center 
staff member will select the appropriate vial of study medication (Section 5.7.5). The 
staff member must follow these application instructions: 
 Wash her/his hands prior to, and after completing the study medication 
applications; after completing the study medication applications wash her/his 
hands while still wearing the examination gloves then dispose of the gloves and 
wash her/his hands again  
 Wear examination gloves during the application 
 Hold the study medication vial away from her/his face and from the subject’s 
face when opening 
 Do not apply the study medications to eyes, nose, mouth, mucous membranes, 
or open wounds 
 Have the subject lie prone with the plane of the target lesion horizontal  
 Thoroughly cleanse the target lesion by firmly rubbing with an alcohol 
swab/wipe to ensure it is clean 
 Using the supplied applicator: 
o Firmly apply a quantity of study medication sufficient to cover the target 
lesion with a thin film 
o Minimize exposure to the surrounding normal skin (excess study 
medication may be removed from the surrounding skin using a clean 
absorbent wipe) 
o Use an application technique that is appropriate for the target lesion size 
and characteristics (e.g., dabbing firmly, with moderate pressure, on 
small or smooth lesions; wiping firmly, with moderate pressure, onto 
large or rough lesions) 
o Repeat firm applications to the target lesion with the applicator 
approximately every 30 seconds, adding study medication to the 
applicator as needed to keep the target lesion wetted, for 5-6 minutes 
o Have the subject remain prone and avoid disturbing the target lesion 
until any visible reaction, if any, has stopped 
o Absorb any remaining study medication and dry the target lesion 
without wiping or rubbing the target lesion.   
 
At Visit 2, repeat these steps to make the initial study medication applications to all 4 
target lesions. 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 30 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
At Visit 5 any target lesion that has a PLA grade of >0, and ONLY target lesions that 
have a PLA grade of >0, must receive a retreatment study medication application 
UNLESS the target lesion: 
 Has a Visit 5 pre-application LSR grade of 3 (severe) for any sign or symptom  
 Is, in the investigator’s opinion, not appropriate for a retreatment study 
medication application. 
 
All Visit 5 retreatment applications will be terminated for all subjects if 4 or more 
subjects discontinue from the study due to study medication related AEs. 
 
At Visit 5, for target lesions that require retreatment, a staff member, other than the 
investigator, will perform the application following the instructions above, using a 
different vial from the vial used for the Visit 2 application. 
 
The investigator is prohibited from access to any study procedure or document that 
shows the study medication identity except in cases of a medical emergency (Section 
5.10.2). 
 
5.7.7. 
Dose compliance record 
At every study visit where a study medication application is performed, an 
investigational center staff member will document the study medication usage in the 
CRF. 
 
5.7.8. 
Dose modification 
Study medication applications will be performed at Visit 2, and if appropriate Visit 5, 
by the investigational center staff at the direction of the investigator, no study 
medication will be dispensed to the study subjects. 
 
If any subject refuses to allow a study medication retreatment application the 
investigator must report the visit number, visit date, target lesion number and the 
reason for the refusal in the subject’s CRFs. If the subject’s refusal is associated with an 
AE, the investigator must report the event on the appropriate CRF (Section 7.2). The 
subject does not need to be removed from the study based solely on her/his refusal to 
have a study medication application on any individual target lesion(s).  
 


Protocol: A-101-SEBK-201 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
5.8. 
Study medication Management 
5.8.1. 
Accountability 
The investigator or designee will maintain an accurate record of the receipt of the study 
medications as shipped by Aclaris Therapeutics, Inc. (or designee), including the date 
received and the condition of the study medications. One copy of this receipt will be 
returned to Aclaris Therapeutics, Inc. (or designee) when the contents of the study 
medication shipment have been verified and one copy maintained in the study file. In 
addition, an accurate study medication disposition record will be kept, specifying the 
amount dispensed for each subject and the date of dispensing. This inventory record 
will be available for inspection at any time. At the completion of the study, the original 
inventory record will be available for review by Aclaris Therapeutics, Inc. upon request. 
5.8.2. 
Return and disposition of study supplies 
At the completion of the study, all used and unused study medication vials will be 
returned to Aclaris Therapeutics, Inc. (or designee) for disposal per Aclaris 
Therapeutics, Inc. (or designee’s) written instructions. 
 
5.9. 
Other Study Supplies 
Aclaris Therapeutics, Inc. will provide: 
 Equipment, supplies and instructions for taking standardized photographs 
 Appropriate equipment to assist the subject with the SSA 
 Supplies for identifying, mapping and tracking the location of the target lesions 
 An appropriate ruler, or other instrument, for measuring the Lesion Dimensions. 
 
A third party will provide the supplies for collecting, labeling, shipping and result 
reporting for the clinical laboratory tests and urine pregnancy tests. 
 
The investigational center will provide appropriate equipment and supplies required 
for collecting, documenting and assessing the study ECGs. 
 
5.10. 
Blinding 
5.10.1. 
Verification of blinding 
Blinding of the study medications is important for validity of this study. This study uses 
a double-blind design. The study medications are indistinguishable in appearance, 
packaging and labeling. 
 
 


Protocol: A-101-SEBK-201 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
5.10.2. 
Un-blinding during the study medication 
Blinding is important for validity of this clinical study. However, the blind may be 
broken in the event of a medical emergency, in which knowledge of the study 
medication identity is critical to the management of the subject’s course of treatment. 
Before breaking the blind the investigator should determine that the information is 
necessary (i.e., that it will alter the subject’s immediate course of treatment). In many 
cases, particularly when the emergency is clearly not study medication-related, the 
problem may be effectively managed by assuming that the target lesion is receiving an 
active study medication without the need for un-blinding.  
 
If deemed necessary to break the blind for a study subject, attempt to contact the Aclaris 
Therapeutics, Inc. Medical Monitor (Section 7.2.2) to obtain concurrence. If it is not 
possible to contact the Medical Monitor beforehand, contact her/him as soon as 
possible after breaking the blind for a subject. 
 
To identify a subject’s study medication, locate the second panel of the tear-off label 
attached to the subject’s Label Page CRF and follow the instructions on the label. Record 
the date of un-blinding, the reason for un-blinding and the initials of the investigational 
center staff member who performed the un-blinding on the subject’s Label Page CRF. 
At the end of the study, the original Label Page CRFs will be returned to the Sponsor 
with a photocopy placed in the investigator’s study file. The original Label Page CRFs 
will be available, upon request, to the site if needed to respond to a regulatory audit. 
 
Any subject whose blind has been broken must be discharged from the study (Section 
4.6).  
 
6. 
STUDY ASSESSMENTS 
The study assessments will be performed according to the schedules noted below by the 
investigator or appropriately trained staff members as noted for each assessment. The 
same individual should perform the assessments for a given subject throughout the 
study. If this becomes impossible, an appropriate designee with overlapping experience 
with the subject and study should perform the assessments. The same lighting 
conditions and the appropriate subject position (see below) should be used for all 
evaluations. 
 
The following evaluations must be performed with the subject standing: 
 SSA (Section 6.1.1) 
 PLA (Section 6.1.2) 
 SSK (Section 6.1.4) 
 LSR (Section 6.2.1). 
 


Protocol: A-101-SEBK-201 
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Page 33 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
The following evaluation may be performed with the subject standing or prone: 
 Lesion Dimensions (Section 6.1.3). 
 
6.1. 
Effectiveness Evaluations 
The investigator and/or subject will evaluate the following for each target lesion. 
 
6.1.1. 
Subject’s Self-Assessment (SSA) 
The SSA must be performed with the subject standing. 
 
The SSA must be completed by the subject BEFORE the investigator performs the PLA.  
 
The SSA is the subject’s assessment of the average overall severity of each target lesion at a 
particular time point and is not a comparison with the SSA at any other time point. The 
subject should NOT refer to any other evaluation to assist with these assessments.  
 
At Visits 2-9, each subject will assess each SK target lesion and report the one integer that 
best describes the average overall severity of each target lesion using the scale below. At 
Visit 2, and if appropriate Visit 5, the SSA must be completed prior to the study 
medication application. 
 
An investigational center staff member must educate the subject on the SSA scale at every 
visit. 
 
To perform the SSA assessment subjects must be provided with a handheld mirror, with 
both 1 power and 2 power magnification, and a full-length (i.e., provides an unobstructed 
view of the target lesion being assessed) mirror. The subject must use the same handheld 
mirror magnification power for all SSA assessments. 
 
To evaluate the target lesions: 
 The subject should stand with her/his back to the full length mirror 
 An investigational staff member will identify each target lesion to the subject in 
numerical order and direct the subject to assess each lesion sequentially 
 The subject should view her/his back using the handheld mirror and full length 
mirror 
 At Visit 2 the staff member will record the handheld mirror magnification power 
the subject used for the assessment (the subject must use the same magnification 
power for all SSA assessments) 
 At Visits 3-9 the staff member will ensure the subject uses the same handheld 
mirror magnification as used for the Visit 2 assessment  
 The staff member should not influence the subject’s assessment. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
The subject should indicate to the staff member the one integer that best describes the 
average overall severity of each target lesion using the following scale. The study staff 
member will report the SSA grade the subject indicates in the source document: 
 
Subject’s Self-Assessment 
Grade 
Descriptor 
0 
Clear: no lesion is noticeable 
1 
Mild: lesion is barely noticeable on careful examination, but is not obvious 
2 
Moderate: lesion is obvious on routine examination  
3 
Severe: lesion is prominent 
 
Both the subject and the study staff member must sign/initial and date the source 
document to indicate the SSA is reported accurately. 
 
6.1.2. 
Physician’s Lesion Assessment (PLA) 
The PLA must be performed with the subject standing. 
 
The investigator must perform the PLA evaluation ONLY AFTER the subject performs the 
SSA and PRIOR to the Signs of Seborrheic Keratosis (SSK). The subject and the 
investigator must not discuss the subject’s SSA grade. 
 
The PLA is the investigator’s assessment of the average overall severity of seborrheic 
keratosis on each target lesion at a particular time point, and is based on the investigator’s 
clinical experience evaluating SK lesions on subjects with similar skin types. The 
investigator should NOT refer to any other assessments to assist with this evaluation.  
 
The PLA grade must be ≥ 2 at Visit 1 for the subject to be enrolled and must be ≥ 2 at 
Visit 2 for the subject to be randomized. 
 
At every study visit, the investigator will assess each seborrheic keratosis target lesion and 
report the one integer that best describes the average overall severity of each using the 
following scale. For this evaluation the subject must stand in a position similar to the 
position used for the SSA (Section 6.1.1). At Visit 2, and if appropriate Visit 5, the 
investigator must perform the PLA prior to the study medication application: 
 
Physician’s Lesion Assessment 
Grade Descriptor 
0 
Clear: no lesion, normal skin 
1 
Mild: lesion is barely evident on examination 
2 
Moderate: obvious lesion  
3 
Severe: severe lesion, prominent 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
6.1.3. 
Lesion Dimensions 
The Lesion Dimensions must be measured with the subject prone.  
 
At every study visit the investigator or designee will measure the following dimensions 
of each target lesion using the ruler, or equivalent, provided: 
 Surface area: 
o The length of the longest axis, in centimeters (cm) to the nearest 0.1cm 
o The length of the longest axis perpendicular to the first measurement, in 
cm to the nearest 0.1cm 
 Thickness: 
o Height, at its highest point above the surrounding skin, in millimeters 
(mm) reported using the categories below. 
 
At Visit 1 and Visit 2 calculate and report the surface area (cm2) of each target lesion by 
multiplying the length of the longest axis in cm and the length of the longest axis 
perpendicular to the first measurement in cm and report to the nearest 0.1cm.  
 
The area of each target lesion must be ≥0.51cm2 and ≤4cm2 at Visit 1 for the subject to be 
enrolled and at Visit 2 for the subject to be randomized. 
 
The lesion thickness of each target lesion must be at least palpable and no more than 
3mm (grade 1-3) at Visit 1 for the subject to be enrolled and at Visit 2 for the subject to 
be randomized. Target lesion thickness will be reported by category: 
 0: No height above surrounding normal skin 
 1: Palpable to ≤1mm 
 2: >1mm and ≤2mm 
 3: >2mm and ≤3mm 
 4: >3mm and ≤4mm 
 5: >4mm. 
 
At Visit 2, and if appropriate Visit 5, the Lesion Dimensions must be measured prior to 
the study medication application. 
 
6.1.4. 
Signs of Seborrheic Keratosis (SSK) 
The SSK must be performed with the subject standing. 
 
The investigator must perform the SSK evaluation ONLY after completing the PLA. 
 
The SSK is the investigator’s assessment of the average severity of two characteristic 
signs of seborrheic keratosis (pigmentation and surface characteristics) on each target 
lesion at a particular time point. The investigator should NOT refer to any other 
evaluations to assist with this evaluation.  


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
 
At Visits 2-9, the investigator will evaluate each seborrheic keratosis target lesion and 
report the one integer that best describes the average severity of each sign of seborrheic 
keratosis for each target lesion using the following scales.  
 
At Visit 2, and if appropriate Visit 5, the investigator must perform the SSK assessment 
prior to the study medication application: 
 
Pigmentation 
Grade Descriptor 
0 
Clear: no variation from normal skin pigmentation 
1 
Mild: mild, but obvious pigmentation 
2 
Moderate: marked pigmentation, may have variegated appearance 
3 
Severe: deeply pigmented lesion, may have variegated appearance 
 
Surface Characteristics 
Grade Descriptor 
0 
Clear: no variation from normal skin surface 
1 
Mild: slightly abnormal  surface (e.g., rough, waxy) evident with thin papular 
or plaque-like appearance 
2 
Moderate: abnormal surface (e.g., rough, waxy), may have verrucous and/or 
cerebriform appearance 
3 
Severe: extremely abnormal surface (e.g., rough, waxy) with verrucous and/or 
cerebriform surface 
 
6.2. 
Safety Evaluations 
6.2.1. 
Local Skin Reactions (LSR) 
The investigator’s portion of the LSR must be performed with the subject standing. 
 
The LSR assessment is the investigator’s and the subject’s assessment of the average 
overall severity of the signs and symptoms, respectively, associated with irritation on a 
target lesion. The investigator and subject must NOT refer to any other evaluation to assist 
with these assessments. This is not a comparison with the assessment at any other time 
point.  
 
 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
Local Skin Reactions: 
 Signs (assessed by the investigator): 
o Erythema 
o Edema 
o Erosion 
o Ulceration 
o Crusting 
o Induration 
o Vesicles/bullae 
o Scaling/dryness 
o Hyper-pigmentation 
o Hypo-pigmentation (a dermal effect; does not include superficial transient 
skin blanching/whitening that may be associated with the study 
medications) 
o Keloid/hypertrophic scarring 
o Atrophy 
 
 Symptoms (assessed by the subject): 
o Stinging/burning 
o Pruritus (itch). 
 
At Visits 2-9 the investigator and the subject will evaluate the LSR signs and symptoms 
respectively for each target lesion.  
 
The subject will assess the LSR for symptoms as follows: 
 At study visits where a study medication application is performed, report the 
average severity of the LSR for symptoms just prior to the start of the study 
medication applications and 10 (±4) minutes after the study medication 
application to the target lesions is completed  
 At study visit where no study medication application is performed, report the 
average severity of the LSR for symptoms over the previous 24 hours. 
 
The investigator will assess the LSR for signs as follows using the scale below: 
 At study visits where a study medication application is performed report the 
average severity of the LSR for signs prior to the start of the study medication 
applications and 20 (±4) minutes after the study medication application to the 
target lesions is completed  
 At study visit where no study medication application is performed report the 
average severity for each sign. 
 
Both the subject and the study staff member will initial and date the source document to 
indicate the subject performed the LSR as instructed. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
To perform the LSR assessment subjects must be provided with a handheld mirror and a 
full-length mirror. 
 
To view the target lesions the subject should: 
 Stand with her/his back to the provided full length mirror 
 View her/his back using the handheld mirror and wall mirror 
 An investigational staff member will identify each target lesion to the subject in 
numerical order and direct the subject to assess the lesion 
 The subject will mark the LSR grade for each symptom on each target lesion on the 
appropriate source document 
 The staff member should not influence the subject’s assessment. 
 
The investigator should report the one integer that best describes average overall 
severity of each LSR sign for each target lesion using the scale below. 
 
Each subject should report the one integer that best describes average overall severity of 
each LSR symptom for each target lesion using the scale below:  
 
Local Skin Reactions 
Grade 
Descriptor 
0 
None 
1 
Mild 
2 
Moderate 
3  
Severe 
 
The investigator must report any LSR that increases in severity, compared to the Visit 2 
pre-application evaluation, by ≥1 grade AND persists for 2 or more successive visits, as 
an AE (Section 7.1). 
 
6.2.2. 
Vital signs 
A qualified staff member will measure the following vital signs at Visit 1, at Visit 2 prior 
to randomization and at Visit 9. At Visit 2 the vital signs should be measured prior to 
any study medication application: 
 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). 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
Any measure that is, in the opinion of the investigator, abnormal AND CR must be 
recorded as history if found prior to the first study medication application at or as an 
AE if found after the first study medication application begins (Section 7.1).  
A systolic blood pressure >140mm Hg or a diastolic blood pressure >100mm Hg is 
considered abnormal and therefore must be defined as clinically relevant (CR) or NCR 
on the comments page of the CRF.  
 
A weight >300 lbs. is considered abnormal and therefore must be defined as CR or NCR 
on the comments page of the CRF.  
 
6.2.3. 
Electrocardiogram (ECG) 
A standard 12-lead ECG will be performed by a qualified staff member at Visit 1, at 
Visit 2 prior to randomization and at Visit 9.  
 
The ECGs must be obtained using a standard 12-lead ECG with a 10mm/mV 
amplitude, at 25mm/sec and 5-10 second duration. To ensure a steady heart rate the 
subject must rest quietly in the supine position for at least 5 minutes prior to performing 
the ECG.  
 
A normal ECG is defined as:  
 QTc 450msec for males and 460msec for females (use of the ECG algorithm is 
acceptable for this purpose) 
 Heart rate that is ≥50 and ≤100 beats/minutes 
 The tracing must not show any: 
o Rhythm disturbance other than a benign sinus dysrhythmia 
o Conduction disturbance including First Degree A-V Block (PR >200msec) 
and pre-excitation (PR <120msec) 
o Acute or chronic signs of ischemia.   
 
Variations such as minor ST changes (i.e., <0.5mm depression) and early re-polarization 
are considered normal.  
 
The ECG results must be interpreted by a qualified health professional (evaluator) and 
the interpretation reported either directly on the tracing or in a separate report. If an 
ECG result is abnormal, the evaluator should describe the abnormality and define the 
abnormality as CR or NCR. The evaluator will record this information directly on the 
ECG tracing/report and date and initial the tracing/report. 
 
The evaluator must review the subject’s Visit 1 ECG prior to Visit 2. The subject must 
not be randomized if the Visit 1 ECG is, in the evaluator’s opinion, abnormal, regardless 
of the clinical relevance.   
 


Protocol: A-101-SEBK-201 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
The evaluator must review all ECG tracings in a timely manner.  
 
The investigator must report all ECG results that are BOTH abnormal AND, in the 
opinion of the evaluator, CR as medical history if found prior to the first study 
medication application at or as an AE if found after the first study medication 
application begins (Section 7.1). 
 
6.2.4. 
Clinical laboratory sampling 
Non-fasting samples for clinical laboratory analysis will be collected by a qualified staff 
member at Visit 1, at Visit 2 prior to randomization and at Visit 9. The following tests, at 
a minimum, will be conducted: 
 
Chemistry Panel 
Complete Blood Count 
Albumin 
Hematocrit 
Alkaline phosphatase 
Hemoglobin 
Alanine aminotransferase (ALT) 
Platelet count 
Aspartate aminotransferase (AST) Red blood cell morphology 
Blood urea nitrogen (BUN) 
Red blood cell count 
Bicarbonate 
White blood cell count 
Calcium 
White blood cell differential 
Chloride 
    % & absolute 
Creatinine 
    Basophils 
Glucose 
    Eosinophils 
Lactate dehydrogenase (LDH) 
    Lymphocytes 
Phosphorus 
    Monocytes 
Potassium 
    Neutrophils 
Sodium 
 
Total bilirubin 
 
Total protein 
 
Uric acid 
 
 
The results of the clinical laboratory tests will be reported on the laboratory’s standard 
reports. The investigator must note NCR or CR to define the clinical relevance of any 
result that is outside the normal range for the laboratory. The investigator must date 
and initial every laboratory report.  
 
The investigator must review the subjects’ Visit 1 laboratory reports prior to Visit 2. The 
subject must not be randomized at Visit 2 if any of the Visit 1 results are outside normal 
range for the laboratory AND, in the opinion of the investigator, CR. 
 
The investigator must review all laboratory reports in a timely manner 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
The investigator must report all laboratory results that are BOTH outside the normal 
range for the laboratory AND, in the opinion of the investigator, CR as medical history 
if found prior to the first study medication application or as an AE if found after the 
first study medication application begins (Section 7.1). 
 
6.2.5. 
Urine pregnancy tests 
The investigator or designee will perform a urine pregnancy test for subjects who are 
WOCBP (Section 8) at Visit 1, at Visit 2 prior to randomization and at Visit 9. The urine 
pregnancy test kits used must have a minimum sensitivity of 25-mIU ß-HCG/milliliter 
(mL) of urine.  
 
Subjects who are WOCBP must have a negative pregnancy test result at Visit 1 to be 
enrolled and at Visit 2 to be randomized. 
 
If the result of any post-randomization urine pregnancy test is positive, the subject will 
be withdrawn from the study and the subject’s pregnancy documented and followed 
(Section 8). 
 
6.3. 
Other Evaluations 
6.3.1. 
Demographics and medical history 
At Visit 1, the investigator or designee will interview each subject to obtain 
demographic information including date of birth, sex at birth, skin type, race and, if 
appropriate, ethnicity.  
 
Medical history information will be recorded including all medical conditions, all 
disease states that require concomitant therapy and other medical conditions and 
disease states that, in the opinion of the investigator, are relevant to the subject’s study 
participation. 
 
6.3.2. 
Standardized photography 
At every study visit standardized color photographs of each target lesion will be taken. 
At Visit 2, and if appropriate Visit 5, the photographs must be taken prior to the study 
medication application. 
  
Care must be taken to ensure the same lighting, background, subject positioning 
relative to the camera and camera settings are used for each photograph. Equipment, 
supplies and detailed instructions for obtaining and managing the photographs will be 
provided to the investigational center prior to the initiation of subject enrollment. 
 
The photographs are to document the appearance of the subjects’ target lesions.  


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
At Visit 1, photographs will be taken as part of the target lesion identification (Section 
5.4). 
 
7. 
ADVERSE EVENTS 
Adverse events will be monitored throughout the study and immediately reported on 
the appropriate Aclaris Therapeutics, Inc. AE CRF.   
 
7.1. 
Definitions 
7.1.1. 
Adverse events (AE) 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a study medication(s) and which does not necessarily have a causal 
relationship with the study medication.  An AE can therefore be any unfavorable and 
unintended sign or symptom associated with the use of a study medication (including 
an abnormal laboratory finding), whether or not related to the study medication.  
 
Thus any new, clinically relevant worsening of an existing sign, symptom or disease, 
should be considered an AE.  
 
Except for Local Skin Reactions, (see below) worsening of any of the target lesion 
assessments must be reported as an AE ONLY if the use of the study medication is 
interrupted or discontinued or if therapy is required to manage the event. Any LSR 
that increases in severity, compared to the Visit 2 pre-application evaluation, by ≥1 
grade AND persists for 2 or more successive visits must be reported as an AE.  
 
The investigator must report the target lesion number(s) for any AE associated with a 
target lesion and should 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.  
 
Every new episode or clinically relevant worsening of a chronic condition (e.g., 
headaches, seasonal allergies, depression, and hypertension) should be reported as a 
separate AE, even if the condition is reported in the subject’s medical history. 
 
The investigator should, when certain, report a diagnosis rather than the signs, 
symptoms or clinically relevant abnormal laboratory values associated with the AE. 
Otherwise, signs, symptoms or abnormal laboratory values may be used to describe the 
AE. 
 
Any CR abnormality discovered prior to the first study medication application should 
be reported as medical history, not as an AE. 
 


Protocol: A-101-SEBK-201 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
7.1.2. 
Serious adverse event (SAE) 
A Serious Adverse Event is any untoward medical occurrence that at any dose: 
 Results in death 
 Is life threatening 
 Requires inpatient hospitalization or prolongation of existing hospitalization 
 Results in persistent or significant disability/incapacity, or 
 Is a congenital anomaly/birth defect 
 Is an important medical event. 
 
The term “life threatening” refers to an event in which the subject was at risk of death at 
the time of event; it does not refer to an event that hypothetically might have caused 
death if it was more severe. 
 
Inpatient hospitalization is considered to have occurred if the subject is admitted to the 
hospital on an in-patient basis, even if released the same day. Prolongation of 
hospitalization is defined as an additional night stay in the hospital. Hospitalization for 
a diagnostic test (even if related to an AE) or elective hospitalization that was planned 
before study enrollment (signing the ICF) are not themselves reasons for an event to be 
defined as a SAE. 
 
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. 
 
7.1.3. 
Unexpected adverse event 
An AE is considered unexpected if it is not listed in the Investigator Brochure or is not 
listed at the specificity or severity that has been observed. 
 
7.1.4. 
Adverse event reporting period 
Non-serious AEs must be reported starting when the subject performs the first study 
medication application until the end of the subject’s last study visit. SAEs must be 
reported starting when the subject signs the ICF until the end of the subject’s last visit. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
7.1.5. 
Severity 
The investigator is to define the severity 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 her/his medical 
judgment. 
 
Mild – Awareness of signs or symptom, but easily tolerated 
Moderate – Discomfort, enough to cause interference with usual activity 
Severe – Incapacitating with inability to perform usual activity. 
 
7.1.6. 
Relationship to study medication 
The investigator will determine if there is a reasonable causal relationship between the 
study medication and an AE or not. The investigator will use her/his best medical 
judgment and consider all relevant factors (e.g., temporal relationship, location of the 
event, the subject’s relevant medical history, concomitant therapies and concurrent 
conditions) to determine the relationship of the AE to the study medication. The 
investigator will define the relationship of an AE to the study medication by selecting 
one of the following categories: 
 
Related – There is a reasonable possibility that there is a causal relationship 
between the study medication and the AE. 
 
Not Related – There is not a reasonable possibility that there is a causal 
relationship between the study medication and the AE. 
 
The term “reasonable causal relationship” means there are facts or arguments to 
suggest a causal relationship (International Conference on Harmonization (ICH) E2A). 
 
7.2. 
Reporting Procedures 
7.2.1. 
Procedures for reporting adverse events 
At each post enrollment visit, the investigator 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 will also question the subject in the same 
manner to elicit AEs during visits when study medication applications are conducted.  
 
If appropriate, based on the subject’s response, directed follow-up questions and 
appropriate evaluations should be conducted.  
 


Protocol: A-101-SEBK-201 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
Any AE noted during the reporting period (Section 7.1.4) must be reported in the source 
documents and on the appropriate AE CRF.  
 
AEs that are defined as “Not Related” to the study medications will be followed until 
they are resolved or until the subject’s last study visit. AEs that are defined as “Related” 
to the study medications will be followed until they are resolved or, if not resolved after 
the subject’s last study visit, until in the opinion of the investigator, the AE reaches a 
clinically stable outcome with or without sequelae. 
 
7.2.2. 
Procedure for reporting a serious adverse event 
Upon becoming aware of a SAE occurring during the AE reporting period, whether or 
not related to the study medications, the investigator must: 
 
1. 
Take the appropriate medical action to ensure the subject’s safety 
2. 
Immediately inform the Medical Monitor of the SAE by telephone: 
 
Stuart D. Shanler, M.D. 
Aclaris Therapeutics, Inc. 
101 Lindenwood Drive 
Suite 400 
Malvern, PA 19355 
Office telephone: (484) 321-5555 
Mobile telephone: (917) 841-9859 
SAE facsimile: (484) 324-2359 
E-mail: sshanler@aclaristx.com 
 
3. 
Within 24-hours complete, as fully as possible, an AE CRF and an SAE form; fax or 
e-mail the forms and any other relevant information (e.g., concomitant medication 
CRF, medical history CRF, laboratory test results) to the Aclaris Therapeutics, Inc. 
Medical Monitor. 
4. 
Monitor and document the progress of the SAE until it resolves or, if not resolved 
after the subject’s last study visit, until in the opinion of the investigator the AE 
reaches a clinically stable outcome with or without sequelae AND the investigator 
and Aclaris Therapeutics, Inc. Medical Monitor agree that the SAE is satisfactorily 
resolved. 
5. 
Inform the Aclaris Therapeutics, Inc. Medical Monitor of SAE updates by 
telephone followed by an SAE form update sent by fax or by e-mail. 
6. 
Comply with the appropriate regulatory requirements and Aclaris Therapeutics, 
Inc. instructions regarding reporting of the SAE to the responsible Institutional 
Review Board (IRB) or Ethics Committee (EC). 


Protocol: A-101-SEBK-201 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
8. 
PREGNANCY 
WOCBP include any female who has experienced menarche and who has not 
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or 
bilateral oophorectomy) or is not postmenopausal (defined as ≥12 months with no 
menses without an alternative medical cause). Women who are using an active method 
of birth control, are practicing abstinence, or where the partner is sterile (e.g., 
vasectomy), should be considered to be WOCBP. 
 
All WOCBP must use an effective method of birth control during the course of the 
study, in a manner such that risk of failure is minimized. Effective methods of birth 
control approved for use in this study are: 
 Implants 
 Injectables 
 Patch 
 Combined oral contraceptives 
 ParaGard® or Mirena® intrauterine devices 
 Condom with spermicide; diaphragm with spermicide 
 Vasectomized partner. 
 
Prior to trial enrollment, WOCBP must be advised of the importance of avoiding 
pregnancy during trial participation and the potential risk factors for a pregnancy.  The 
subject must sign an informed consent form documenting this discussion.  During the 
trial all WOCBP will be instructed to contact the investigator immediately if they 
suspect they might be pregnant (e.g., missed or late menstrual period). 
 
If a subject or investigator suspects that the subject may be pregnant prior to study 
medication administration, the study medication must be withheld until the results of a 
pregnancy test are available.  If pregnancy is confirmed, the subject must not receive 
study medication and must be discharged from the study.  
 
If, following study medication administration, it is determined that the subject may 
have been or was pregnant at the time of study medication exposure (including at least 
2 days after study medication administration) the investigator must immediately notify 
the Aclaris Therapeutics, Inc. Medical Monitor and record the event on a pregnancy 
surveillance form. While not an AE or SAE, every pregnancy must be reported using a 
pregnancy surveillance form and follow the reporting procedures described for SAE 
reporting (Section 7.2.2). 


Protocol: A-101-SEBK-201 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
                                                                                                                                              
Protocol-required procedures for trial discontinuation and follow-up must be 
performed on the subject unless contraindicated by pregnancy (e.g., x-ray studies). 
Other appropriate pregnancy follow-up procedures should be considered if indicated. 
In addition, the investigator must report to Aclaris Therapeutics, Inc.’s Medical Monitor 
on the pregnancy surveillance form, follow-up information regarding the course of the 
pregnancy, including perinatal and neonatal outcome. Infants should be followed for a 
minimum of six weeks. 
  
9. 
STATISTICAL ANALYSES 
9.1. 
Statistical Analysis of Clinical Indices 
The primary effectiveness analyses will be pairwise comparisons between Vehicle and 
each active study medication, based on mean change from Visit 2 PLA, using a 
repeated-measures Analysis of Covariance model suitable for the study design.  Study 
medication concentration is the within-subject independent variable.  The Visit 2 score 
will be the covariate.  The primary analysis visit will be Visit 9.  An exploratory dose-
response analysis may be conducted across concentrations to evaluate a concentration 
trend, as well as an exploratory longitudinal analysis across visits to evaluate trends 
over time. 
 
Secondary efficacy analyses will include a similar analysis of SSA, SSK and other 
evaluations suitable for analysis as continuous variables.  Separate primary and 
secondary effectiveness analyses at each post-baseline visit will be conducted.  In 
addition, secondary analyses will be performed on proportion of PLA and SSA 
responders, where a subject will be considered a responder if the Visit 9 score is 0. A 
similar analysis will be done at Visit 5. Chi-square will be used to analyze differences in 
response rates under the assumption that lesions within a subject may be treated 
independently, along with a repeated-measures logistic regression model applied as an 
optional exploratory analysis method. 
 
For all analyses two-tail alpha will be set at 0.05 with no adjustment for multiplicity due 
to the exploratory nature of the study.  The Intent-to-Treat (ITT) population, defined as 
subjects with data for both Visit 2 and at least one post-Visit 2, will be the primary 
analysis population, supplanted by analyses of the Per-Protocol (PP) population 
defined as ITT subjects with no missing effectiveness data and no major protocol 
violations. ITT population analyses will use last-observation-carried-forward to impute 
missing post-Visit 2 data. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
9.2. 
Statistical Analysis of Safety Data 
Descriptive statistics will be calculated on the safety parameters using the intent-to-treat 
population, defined as those subjects who were randomized and received at least one 
study medication application.  The proportion of subjects with treatment-emergent 
adverse events will be tabulated and presented by treatment and Medical Dictionary for 
Regulatory Activities (MedDRA) System Organ Class.  Vital signs, clinically-relevant 
ECG results, LSR scores and clinically-relevant abnormal laboratory results will also be 
tabulated and presented by study medication and abrasion cohort.  No inferential 
testing will be performed. 
 
Data from all randomized subjects will be presented and summarized. Safety 
summaries by study medication group will include listings by study medication of 
adverse events incidences within each MedDRA System Organ Class, and changes from 
pre-application values in vital signs.  Adverse event summaries will be presented by 
study medication showing the proportion of subjects experiencing adverse events, both 
overall and by MedDRA System Organ Class. 
 
9.3. 
Sample Size 
The sample size of 32 subjects completing this study was based on the estimated 
primary efficacy variable response rates for the most effective active medication and 
vehicle, which are expected to be approximately 60% and 10% respectively.  This 
difference is expected to yield approximately 88% power using a standard chi-square 
test under the assumption of lesion independence. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
10. 
TRAINING, MONITORING, DATA MANAGEMENT AND QUALITY 
ASSURANCE 
10.1. 
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 prior to 
participating in any of the procedures and evaluations in this study.  
 
Clinical Research Associates (CRAs) and other applicable personnel will be trained 
prior to study initiation to familiarize CRAs with the disease, the Standard Operating 
Procedures (SOPs), the protocol and other study specific items.  Team organization, 
communication and operational issues will also be discussed. 
 
Aclaris Therapeutics, Inc. will provide an investigational center file to each center. 
 
10.2. 
Monitoring 
The conduct of the study will be closely monitored by representatives of Aclaris 
Therapeutics, Inc. to verify adherence to ICH Good Clinical Practice (GCP) guidelines 
and applicable SOPs.  Reports of these verifications will be archived with the study 
report.  The investigator will allow the Aclaris Therapeutics, Inc. representatives 
designee and/or and any regulatory agency to have direct access to all study records, 
CRFs, corresponding subject medical records, study medication dispensing records and 
study medication storage area, and any other documents considered source 
documentation.  The investigator also agrees to assist the representative, if required. 
 
10.3. 
Data Management 
Data-management activities of this study will be sub-contracted. 
 
Edit checks and review processes will be performed by the sub-contractor until all data 
clarifications are resolved. The data will be exported to be stored in SAS datasets (or 
equivalent) by the sub-contractor. After all data clarifications are resolved and subject’s 
evaluability is determined, the database will be locked. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
10.4. 
Quality Assurance 
The study is conducted under the sponsorship of Aclaris Therapeutics, Inc. in 
compliance with the applicable regulatory requirements as well as applicable ICH 
guidelines, Helsinki Declaration, and in respect of the Aclaris Therapeutics, Inc. and/or 
sub-contractor SOPs for study conduct and monitoring. 
 
Audits may be carried out by the Aclaris Therapeutics, Inc. or Aclaris Therapeutics, 
Inc.’s representatives and inspections may be performed by regulatory authorities or 
IRB/ECs before, during or after the study.  The investigator will provide the 
auditing/inspecting group direct access to all study records (e.g., CRFs, subject medical 
records, study medication dispensing records) and the investigational center study 
facilities. The investigator and study staff will be available and will assist the 
auditing/inspecting groups as appropriate.  
 
11. 
ETHICS AND GENERAL STUDY CONDUCT CONSIDERATIONS 
11.1. 
Institutional Review Board (IRB)/Ethics Committee (EC) 
This protocol, informed consent form, any information provided to subjects, subject 
recruiting advertisements, and any amendments to these items will receive IRB/EC 
approval prior to use. 
 
The IRB/EC must receive a copy of the Investigator’s Brochure, all protocol 
amendments, safety reports and other study related information as required by 
regulation or the IRB/EC procedures. 
 
11.2. 
Ethical Conduct of the Study 
The rights, safety and well-being of the subjects are the most important considerations 
in this study and take priority over the interests of society and science.  
 
This study will be conducted in accordance with the ethical principles originating from 
the Declaration of Helsinki, the ICH E6 GCP guideline, local regulatory requirements 
and, at US investigational centers, in compliance with the HIPAA. The study will be 
conducted in compliance with the IRB/EC approved version of the protocol and any 
applicable amendments. 
 
This protocol, informed consent form, any information provided to subjects, subject 
recruiting advertisements, and any amendments to these items will receive IRB/EC 
approval prior to use. Subjects will provide voluntary informed consent prior to 
initiation of any study related procedures. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
11.3. 
Subject Information and Consent 
All subjects who participate in this study must be fully informed about the study in 
accordance with the GCPs, federal regulations, local regulations and, at US 
investigational centers, with HIPAA.  The ICF will contain all the required elements in 
compliance with the current ICH E6 GCP guideline, local regulatory requirements and, 
at US investigational centers, in compliance with HIPAA.  
 
The investigator must have a defined process for obtaining voluntary informed consent 
from every subject.  
 
The ICF, approved by an IRB/EC, will be fully explained to the subject.  Prior to any 
study related procedures, including washout from therapies, the subject will voluntarily 
sign and date the ICF. The investigator must maintain each subject’s ICF in the 
investigational center’s study file and must provide each subject with a copy of the 
signed and dated ICF. 
 
11.4. 
Study Conduct and Protocol Amendments 
With the exception of eliminating an immediate hazard to a subject, the investigator 
should not deviate from the protocol or implement any changes without prior written 
approval from the Aclaris Therapeutics, Inc. and prior review and documented 
approval from the IRB/EC. 
 
Changes that involve only logistical or administrative changes are allowed.  The 
investigator should document and explain any deviation from the protocol. 
 
11.5. 
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. 
 
11.6. 
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. 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
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Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
11.7. 
Data Collection and Archiving 
11.7.1. 
Data collection  
The Investigator must maintain required records for all study subjects.  Data for this 
study will be recorded in the subject's source document and on the CRFs.  All data on 
these CRFs should be recorded completely and promptly.  A copy of the completed 
CRFs for each subject will be retained by the investigational center. 
 
11.7.2. 
Source documentation 
Investigators must keep accurate separate records (other than the CRFs) of all subjects' 
visits that include all pertinent study related information.  A statement should be made 
indicating that the subjects have been enrolled in this clinical study, and have provided 
written informed consent.  Any AEs must be completely documented. 
 
Source documentation includes results of any diagnostic tests conducted during the 
study.   
 
11.7.3. 
Archiving 
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. /contract research organization/investigator archives for 
the legally required duration for archiving. 
 
The investigator should maintain the essential study documents as specified in ICH 
GCP, and in compliance with all regulatory requirements. The investigator should 
ensure these documents are protected from accidental destruction or disposal. 
 
If the Investigator needs to re-assign responsibility for maintaining these documents 
(e.g., due to retirement) it must be transferred to a person willing to accept this 
responsibility.  The investigator must notify the Aclaris Therapeutics, Inc., in writing, of 
the name and address of the new individual. 
 
 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 53 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
12. 
SUBJECT INSTRUCTION SHEET 
The investigator should dispense a copy of this instruction sheet  
to each subject at Visit 1 (Section 5.3.1). 
 
 


Protocol: A-101-SEBK-201 
Revised protocol number: 1 
Aclaris Therapeutics, Inc. 
 
 
Page 54 of 54 
Date: 05-NOV-2013                                                                                                    Supersedes: NEW 
A-101-SEBK-201 SUBJECT INSTRUCTION SHEET 
Please follow these instructions carefully. Contact the study staff at the telephone 
number noted below if you have any questions about the study: 
 
Contact: 
 
 
 
 
 
   Telephone:                                      
DURING THE STUDY: 
 Continue your routine cleansing regimen except avoid vigorous scrubbing of the 
back (e.g., loofah, back brushes, scrubbing straps, abrasive cleansing pads, etc.) 
 Continue your routine cosmetics and skin care products 
 Do not apply any topical products to the target lesions (except sunscreens as 
described below) 
 Avoid exposing your back to excessive natural or artificial ultraviolet radiation 
(e.g., sunlight, tanning beds) and use sunscreen on your back, including on the 
target lesions, if excessive exposure cannot be avoided 
 Starting at Visit 1 and continuing until study completion, avoid or modify activities 
(e.g., vigorous exercise, carrying heavy backpacks, back massages) and clothing 
(e.g., bras, compression clothing) that might irritate the target lesions 
 Bring this subject instruction sheet with you to each visit. 
 
ON STUDY VISIT DAYS: 
 Wear a loose fitting blouse/shirt as instructed by the study staff so it is easier for 
the investigator to examine the target lesions (NOTE: clothing that comes in 
contact with the study medication may be bleached) 
 Do not apply any topical products to your back within 12 hours prior to the visit, 
routine cleansing products are allowed 
 After visits when a study medication application is performed do not: 
o Apply any topical products to your back for at least 6 hours  
o Wash/submerge your back for at least 6 hours. 
 
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: 
Thank you for following these instructions