Conditions: Atopic Dermatitis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 22
Healthy volunteers: no

Brief summary:
This is an open label, multicenter study designed to evaluate the safety and tolerability of ATI-502 Topical Solution in male and female subjects with moderate or severe atopic dermatitis (AD). Subjects will be required to apply ATI-502 study medication to their identified AD treatment areas. All subjects will be required to complete a safety follow up visit 4 weeks post last study medication application

Detailed description:

Arms:
arm 1: ATI-502 topical solution applied daily for four weeks.

Interventions: intervention 1: ATI-502
Intervention descriptions: intervention 1: Topical Solution

Protocol document:
Prot_000.pdf: 
Protocol:  ATI-502-AD-201 
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Amendment 1 
 
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CLINICAL STUDY PROTOCOL 
PROTOCOL NUMBER ATI-502-AD-201 
A PHASE 2A SAFETY STUDY OF ATI-502 TOPICAL SOLUTION IN SUBJECTS 
WITH MODERATE TO SEVERE ATOPIC DERMATITIS  
 
 
Sponsor 
Aclaris Therapeutics, Inc. 
640 Lee Road, Suite 200 
Wayne, PA 19087 
Telephone: (484) 324-7933 
Facsimile: (484) 320-2344 
 
Study Contact 
Judy Schnyder 
Aclaris Therapeutics, Inc. 
Telephone:  484-329-2144 
Email:  jschnyder@aclaristx.com 
 
Medical Monitor        
Stuart D. Shanler, MD 
Aclaris Therapeutics, Inc. 
Telephone:  484-321-5555 
Email:  sshanler@aclaristx.com 
 
 




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INVESTIGATOR’S AGREEMENT 
 
Protocol Number:  ATI-502-AD-201  
 
Protocol Title: A Phase 2a Safety Study of ATI-502 Topical Solution in Subjects with Moderate to 
Severe Atopic Dermatitis 
 
I have reviewed the above-titled protocol and agree that it contains all the information necessary to 
conduct the study as required.  I will conduct the trial in accordance with the principles of ICH Good 
Clinical Practice and the Declaration of Helsinki. 
I will maintain as confidential all written and verbal information provided to me by the Sponsor, 
including but not limited to, the protocol, case report forms, investigator’s brochure, material supplied at 
investigator meetings, minutes of teleconferences, etc.  Such materials will only be provided as necessary 
to site personnel involved in the conduct of the trial, involved IRBs or local regulatory authorities. 
I will obtain written informed consent from each prospective trial subject or each prospective trial 
subject’s legal representative prior to conducting any protocol-specified procedures.  The Informed 
Consent Document used will have the approval of the IRB appropriate for my institution. 
 
I will maintain adequate source documents and record all observations, treatments and procedures 
pertinent to trial subjects in their medical records.  I will accurately complete the case report forms 
supplied by the Sponsor in a timely manner.  I will ensure that my facilities and records will be available 
for inspection by representatives of the Sponsor, the IRB, and/or local regulatory authorities.  I will 
ensure that I and my staff are available to meet with Sponsor representatives during regularly scheduled 
monitoring visits. 
I will notify the Sponsor within 24 hours of any serious adverse events.  Following this notification, a 
written report describing the serious adverse event will be provided to the Sponsor as soon as possible. 
 
Investigator Signature: 
 
 
____________________________________ 
________________________ 
Investigator signature 
 
Date 
 
 
 
____________________________________ 
Investigator printed name  


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1. 
AMENDMENT HISTORY 
1.1. 
Amendment Rationale 
The original protocol dated 23 April 2018 has been amended to change the heart rate inclusion 
criteria to allow subjects to enter the study if they have a heart that is below 45 or above 100 that 
is not deemed clinically significant by the investigator.  The rationale for this change is ensure 
that subjects are not excluded from the subject that are clinically stable based upon the treating 
physician’s judgement.  The protocol was also amended to allow subjects to enter the study even 
though their screening photographs were not approved by the panel of 3 dermatologists. The 
rationale for this change is that due to flash photography and the close-up images of the photos 
there may be instances in which the photos do not accurately represent the disease status.  If a 
subject’s screening photographs are rejected by the review panel, the treating physician will be 
contacted to review the individual case and allow his/her clinical judgement of the subject to 
over-ride the photo review assessment.       
1.2. 
Protocol Changes 
Protocol 
Version 
Date 
Section 
Revisions 
Version 
1.0 
 
NA 
Original Protocol  
Version 
2.0 
17 August 
2018 
 
 
 
 
Synopsis 
Revised exclusion criteria number 14 to read that 
subjects with a resting heart rate ≤ 45 or Heart Rate ≥ 
100 beats/minutes if considered to be caused by a 
clinically significant pathology would be excluded.  The 
investigator may enter a patient with a HR outside of 
these values if considered to have no clinical 
significance. 
 
 
Section 7.5 
Revised text to allow those subjects that may have been 
rejected by the panel reviewers based on screening 
photographs to be enrolled if the treating physician does 
not feel that the photographs represent the true state of 
the disease.  New text added:  In cases where the 
photographs do not properly characterize the disease 
(due to flashback and whitening on the photographs) the 
subjects will be allowed to enroll to the study based upon 
the Principal Investigator’s clinical assessment of the 
subject. 
 
 
Section 8.0 
Updated table of assessments to include language 
regarding the review of subject screening photos.  
Following language added to footnote 8:  In cases where 
the photographs do not properly characterize the disease 
(due to flashback and whitening on the photographs) the 
subjects will be allowed to enroll to the study based upon 
the Principal Investigator’s clinical assessment of the 
subject. 


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Protocol 
Version 
Date 
Section 
Revisions 
 
 
Section 9.3 
Revised exclusion criteria number 14 to read that 
subjects with a resting heart rate ≤ 45 or Heart Rate ≥ 
100 beats/minutes if considered to be caused by a 
clinically significant pathology would be excluded.  The 
investigator may enter a patient with a HR outside of 
these values if considered to have no clinical 
significance. 
 
 
Section 12.1 
Deleted the text :  All identified target treatment areas 
will be assessed using the Physician’s Global 
Assessment at Visits 1, 2, 3, 4, 5 and 6. Any new 
areas of AD that develop after Visit 2 will not be 
assessed by the PGA.  
 
 
Section 12.6 
Updated section to add in the following text:  In cases 
where the photographs do not properly characterize the 
disease (due to flashback and whitening on the 
photographs) the subjects will be allowed to enroll to the 
study based upon the Principal Investigator’s clinical 
assessment of the subject. 
 


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2. 
SYNOPSIS 
Name of Sponsor/Company: 
Aclaris Therapeutics, Inc.  
Name of Investigational Product: 
ATI-502 Topical Solution, 0.46%  
Protocol Number: ATI-502-AD-201 
Phase:  2a 
Country:  USA 
Title of Study:  
A Phase 2a Safety Study of ATI-502 Topical Solution in Subjects with Moderate to Severe Atopic 
Dermatitis 
Study center(s):  Approximately 6 US investigational sites will participate in the study.   
Studied period (years):  
Estimated date first patient enrolled: June 2018 
Estimated date last patient completed: Dec 2018 
Phase of development:  
2a 
Study Outcome Measures:  
Primary: 
The primary outcome measure for this study is to assess the safety and tolerability of ATI-502 
Topical Solution, 0.46% in subjects with moderate to severe atopic dermatitis.   
Secondary: 
The secondary outcome measures for this study are to assess the following: 
• 
Change from baseline in Physician Global Assessment (PGA) score following 4 weeks of 
treatment with ATI-502 Topical Solution, 0.46% 
• 
Change from baseline in body surface area affected by atopic dermatitis following 4 
weeks of treatment with ATI-502 Topical Solution, 0.46%. 
• 
Change from baseline in Eczema Area and Severity Index (EASI) score following 4 
weeks of treatment with ATI-502 Topical Solution, 0.46%.  
• Change from baseline in the subjects Signs of Atopic Dermatitis (SAD) 
assessment following 4 weeks of treatment with ATI-502 Topical Solution, 
0.46%. 
• 
Change from baseline in Subjects Pruritis Assessment (SPA) score following 4 weeks of 
treatment with ATI-502 Topical Solution, 0.46%. 
Study Design:  This is an open label, multicenter, phase 2a study designed to evaluate the safety and 
tolerability of ATI-502 Topical Solution, 0.46% in male and female subjects with moderate or severe 
atopic dermatitis (AD) as defined by the Hanifin and Rajka criteria.  Subjects will be required to 
apply ATI-502 study medication to their identified AD treatment areas twice a day for a total of 4 
weeks.  Subjects will be allowed to treat new disease areas if they appear after Visit 2.  All subjects 
will be required to complete a safety follow up visit 4 weeks post last study medication application.     
Number of subjects (planned):  
30 subjects with moderate to severe atopic dermatitis 


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Inclusion Criteria:  
Subjects must meet the following criteria to be eligible for participation in the study: 
1. Able to comprehend and willing to sign an Informed Consent Form (ICF). 
2. Male or non-pregnant, non-nursing female subjects ≥ 18 years old at the time of 
informed consent. 
3. Subject must have diagnosis of AD according to the Hanifin and Rajka criteria. 
4. Subject must have a diagnosis of moderate (PGA =3) or severe (PGA=4) AD for a 
period of ≥6 months prior to the first dose of study medication (Visit 2).   
5. Subject Visit 1 photographs are approved for enrollment by the dermatology review 
panel. 
6. Body surface area involvement must be between 2-20% (excluding scalp, face, palms 
of hands, soles of feet, groin and genitalia). 
7. Subject must have an absolute neutrophil count and a platelet count within normal 
range. 
8. Subject must be willing to refrain from washing area of treatment or swimming for 6 
hours after each treatment application with ATI-502. 
9. Subject must be willing to refrain from excess of sun exposure.   
10. Subject is willing and able to follow all study instructions and be willing to attend all 
study visits.   
11. Subjects must refrain from participating in strenuous exercise that would cause 
profuse sweating for a period of 6 hours after each treatment application with ATI-
502.   
12. Subject must refrain from using moisturizers, emollients, and sunscreen on target AD 
treatment area for the duration of protocol therapy.   
13. Be in good general health and free of any known disease state or physical condition 
which, in the investigator’s opinion, might impair evaluation of the subject or which 
might expose the subject to an unacceptable risk by study participation. 
14. If a woman of childbearing potential (WOCBP), must have a negative serum 
pregnancy test at Screening (Visit 1) and a negative urine pregnancy test at Baseline 
(Visit 2) and agree to: use a highly effective method of birth control for the duration 
of the study; not be planning a pregnancy during the study duration and use 
contraception for 30 days after last application of study medication. 
15. Sexually active male subjects must agree to use a barrier method of contraception 
from the first application of study medication to at least 30 days after the last 
application of study medication. 
 
Exclusion Criteria: 
1. Subject has any signs or symptoms associated with AD therapy (e.g., history of 
anaphylaxis, hypersensitivity reactions, skin atrophy, striae, pigmentary changes) 
which, in the investigator’s opinion, might impair evaluation of the AD or which 
exposes the subject to unacceptable risk by study participation.   
2. Subjects unable to complete the following required washout periods: 
• Phototherapy within 4 weeks prior to Visit 1.   
• Systemic immunosuppressant or immunomodulatory therapy (e.g. etanercept, 
alefacept, infliximab, methotrexate) within 16 weeks prior to Visit 1. 
• JAK inhibitors (systemic and topical) within 4 weeks prior to Visit 1. 


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• Systemic corticosteroids (intranasal and inhaled corticosteroids are allowed) 
within 4 weeks prior to Visit 1.  
• Cytostatic agents within 4 weeks prior to Visit 1. 
• Crisaborole within 2 weeks prior to Visit 1 
• Dupilumab or other monoclonal antibody within 3 months prior to Visit 1. 
• Systemic antibiotics with 2 weeks prior to Visit 1. 
• Topical treatments for atopic dermatitis (corticosteroids, calcineurin inhibitors, 
topical H1 and H2 antihistamines, topical antimicrobials, and other medicated 
topical agents) within 1 week prior to Visit 1.   
• Live attenuated vaccine treatment within 12 weeks prior to Visit. 
3. Use of prescription moisturizers within 7 days of Visit 1.    
4. Subject has used any emollients/moisturizers on the planned treatment area (s) within 
4 hours of Visit 1.   
5. Subject has clinically infected AD.  
6. Subject is currently using an oral H1 antihistamines (e.g. diphenhydramine, 
terfenadine) UNLESS the subject is on a stable dose for at least 14 days prior to Visit 
1.  
7. Clinically significant laboratory abnormalities at Visit 1 that, in the opinion of the 
Investigator, would make the subject a poor candidate for the study. 
8. History of, or current, severe, progressive or uncontrolled renal, hepatic, 
gastrointestinal, pulmonary, cardiovascular, genitourinary (renal disease) or 
hematological disease, neurologic or cerebral disorders, infectious disease or 
coagulation disorders that, as determined by the Investigator, would preclude 
participation in and completion of study assessments. 
9. History of, current or suspected systemic or cutaneous malignancy and /or 
lymphoproliferative disease, other than subjects with: a history of adequately treated 
and well healed and completely cleared non-melanoma skin cancers (basal or 
squamous cell carcinoma) treated successfully at least 1 year prior to study entry with 
no evidence of disease. 
10. Evidence of active or latent bacterial (including tuberculosis) or viral infections at the 
time of enrollment or history of incompletely treated or untreated tuberculosis.  
Subjects who have completed therapy for latent tuberculosis may participate. 
11. History of a serious local infection (e.g., cellulitis, abscess) or systemic infection 
including but not limited to a history of treated infection (e.g., pneumonia, 
septicemia) within 3 months prior to Visit 2. Subjects on an antibiotic for a non-
serious, acute local infection must complete the course prior to enrollment into the 
study. 
12.  Positive serological test for HIV (antibody), HCV (antibody), or HepB (HBsAg).   
13. Subjects with herpes zoster or cytomegalovirus (CMV) that resolved less than 2 
months before study enrollment. Subjects with a history of frequent outbreaks of 
Herpes Simplex Virus (defined as 4 or more outbreaks a year). 
14.   Screening ECG findings of: 
a. QTcF >450msec for males or >470msec for females (use of the ECG algorithm is 
acceptable for this purpose). 


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b. Resting heart rate ≤ 45 or Heart Rate ≥ 100 beats/minutes if considered to be 
caused by a clinically significant pathology.  The investigator may enter a patient 
with a HR outside of these values if considered to have no clinical significance. 
c. Rhythm disturbance other than sinus arrhythmia or ectopic supraventricular 
rhythm (ectopic atrial rhythm). 
d. Conduction disturbance including PR >240msec, pre-excitation (delta wave and 
PR <120msec), second degree or higher AV block. 
e. Acute or chronic signs of ischemia.  
f. Left Bundle Branch Block. 
g. Prior myocardial infarction. 
15. Subject has participated in an investigational drug trial within 30 days prior to Visit 1.   
 
Investigational product, dosage and mode of administration:  
Open label ATI-502 Topical Solution, 0.46% will be applied to the identified target treatment AD 
areas twice a day for 4 weeks.  The ATI-502 study medication will be supplied in amber, glass bottles 
and subjects will use disposable droppers to apply the topical solution to their treatment areas.   
Duration of treatment:  
All subjects will apply ATI-502 Topical Solution, 0.46% twice a day for 4 weeks followed by a post 
treatment follow up visit at week 8.   
 
Statistical methods:  
Safety and efficacy results will be summarized and presented by visit, with no inferential statistics 
presented.  Parameters related to safety and tolerability will be treated as primary analysis variables.  
Efficacy parameters will be treated as secondary endpoints. 
 
All data will be summarized by visit, with presentations based on the nature of the parameter.  For 
binary data such as presence or absence of treatment-emergent adverse events, the incidence will be 
presented along with the overall number of subjects and percentages.  External clinical laboratory and 
similar externally sourced data will be summarized as binary outcomes based on the determination of 
values beyond applicable normal ranges, and in some cases the assessment of clinical significance of 
deviations from normal ranges.  For ordinal categorical data including efficacy data from PGA, EASI, 
SPA and SAD scores, and continuous data such as affected body surface area, summary statistics will 
be presented including N, mean, median, standard deviation, and standard error, by visit.  Where 
applicable, the mean changes from baseline for ordinal categorical and continuous parameters will be 
presented by visit, along with N, median, standard deviation and standard error. 
 
Analysis of Efficacy Outcome Measures: 
Subject responder analyses will be conducted, by visit, based on the following criteria: 
 
• 
The proportion of subjects whose active-treated lesions are judged to be clear or near clear on 
the PGA (PGA = ≤ 1) with a 2 grade or greater improvement from a baseline score of PGA=3 
or PGA =4; 
• 
The proportion of subjects whose active-treated lesions are judged to be clear on the PGA 
(PGA = 0);  


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• 
The proportion of subjects who had an improvement from baseline of at least 75% in EASI 
score (EASI – 75). 
Other subject responder criteria will be established as appropriate from data observation and the 
results will be presented as above.   
 


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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
PROTOCOL APPROVAL SIGNATURE PAGE ...........................................................................2 
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
1. 
AMENDMENT HISTORY ..........................................................................................4 
1.1. 
Amendment Rationale ..................................................................................................4 
1.2. 
Protocol Changes ..........................................................................................................4 
2. 
SYNOPSIS ...................................................................................................................6 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............11 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................15 
5. 
INTRODUCTION ......................................................................................................17 
5.1. 
Overview of Atopic Dermatitis ..................................................................................17 
5.2. 
Rationale for the use of ATI-502 in Atopic Dermatitis ..............................................17 
6. 
TRIAL OUTCOME MEAURES AND PURPOSE ...................................................18 
6.1. 
Primary Outcome Measure .........................................................................................18 
6.2. 
Secondary Outcome Measures ...................................................................................18 
7. 
INVESTIGATIONAL PLAN .....................................................................................19 
7.1. 
Overall Study Design ..................................................................................................19 
7.2. 
Number of Subjects ....................................................................................................19 
7.3. 
Duration of Treatment ................................................................................................19 
7.4. 
Treatment Assignment ................................................................................................19 
7.5. 
Enrollment Procedures ................................................................................................19 
7.6. 
Subject Identifiers .......................................................................................................20 
7.7. 
Replacement of Subjects .............................................................................................20 
7.8. 
Criteria for Study Termination ...................................................................................20 
8. 
STUDY PROCEDURES ............................................................................................21 
9. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................23 
9.1. 
Subject Inclusion Criteria ...........................................................................................23 
9.2. 
Subject Exclusion Criteria ..........................................................................................24 
9.3. 
Subject Withdrawal Criteria .......................................................................................25 
10. 
STUDY MEDICATION AND MANAGEMENT .....................................................27 


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10.1. 
Description of Study Drug ..........................................................................................27 
10.2. 
Subject Randomization ...............................................................................................27 
10.3. 
Study Drug Packaging, Labeling and Storage ............................................................27 
10.4. 
Study Drug Accountability and Disposal ...................................................................28 
10.5. 
Additional Clinical Supplies .......................................................................................28 
11. 
TREATMENT OF SUBJECTS ..................................................................................29 
11.1. 
Identification of Target Treatment Area .....................................................................29 
11.2. 
Application of Investigational Product .......................................................................29 
11.3. 
Study Medication Interruption ....................................................................................29 
11.4. 
Skin Care while on Study ...........................................................................................30 
11.5. 
Concomitant Medications ...........................................................................................30 
11.6. 
Prohibited Medications ...............................................................................................31 
11.7. 
Treatment Compliance ................................................................................................31 
12. 
STUDY ASSESSMENTS ..........................................................................................32 
12.1. 
Physician’s Global Assessment (PGA) ......................................................................32 
12.2. 
Body Surface Area (BSA) ..........................................................................................32 
12.3. 
Eczema Area and Severity Index (EASI) ...................................................................32 
12.4. 
Signs of Atopic Dermatitis (SAD) ..............................................................................34 
12.5. 
Subjects Pruritis Assessment (SPA) ...........................................................................36 
12.6. 
AD Treatment Area Photography ...............................................................................36 
13. 
ASSESSMENT OF SAFETY .....................................................................................38 
13.1. 
Safety Parameters .......................................................................................................38 
13.1.1. 
Demographic/Medical History ...................................................................................38 
13.1.2. 
Vital Signs ..................................................................................................................38 
13.1.3. 
Physical Examination .................................................................................................38 
13.1.4. 
Electrocardiogram (ECG) ...........................................................................................38 
13.1.5. 
Pregnancy Testing ......................................................................................................39 
13.1.6. 
Laboratory Assessments .............................................................................................39 
13.1.7. 
Virus Serology ............................................................................................................40 
13.2. 
Adverse and Serious Adverse Events .........................................................................40 
13.2.1. 
Definition of Adverse Events .....................................................................................40 
13.2.1.1. 
Adverse Event (AE) ....................................................................................................40 
13.2.1.2. 
Serious Adverse Event (SAE) ....................................................................................40 


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13.2.1.3. 
Unexpected adverse events .........................................................................................41 
13.3. 
Recording of Adverse Events .....................................................................................41 
13.3.1. 
Adverse event reporting period ..................................................................................41 
13.3.2. 
Severity .......................................................................................................................41 
13.3.3. 
Relationship to study medication ................................................................................41 
13.3.4. 
Procedures for reporting adverse events .....................................................................42 
13.3.5. 
Procedure for reporting a serious adverse event .........................................................42 
13.4. 
Pregnancy ...................................................................................................................43 
13.4.1. 
Definition of Woman of Child Bearing Potential (WOCBP) .....................................43 
13.4.2. 
Highly Effective Methods of Birth Control ................................................................43 
14. 
STATISTICS ..............................................................................................................45 
14.1. 
Statistical Methods ......................................................................................................45 
14.2. 
Analysis of Efficacy Outcome Measures ...................................................................45 
15. 
TRAINING, DATA HANDLING AND RECORDKEEPING ..................................46 
15.1. 
Training .......................................................................................................................46 
15.2. 
Data Collection ...........................................................................................................46 
15.3. 
Protocol Violations and Deviations ............................................................................46 
15.4. 
Study Monitoring ........................................................................................................46 
15.5. 
Source Documentation ................................................................................................47 
15.6. 
Inspection of Records .................................................................................................47 
15.7. 
Retention of Records ..................................................................................................48 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................49 
17. 
ETHICS ......................................................................................................................50 
17.1. 
Ethics Review .............................................................................................................50 
17.2. 
Ethical Conduct of the Study ......................................................................................50 
17.3. 
Written Informed Consent ..........................................................................................50 
17.4. 
Study Conduct and Protocol Amendments .................................................................50 
17.5. 
Regulatory Documents ...............................................................................................51 
17.6. 
Contractual Requirements ..........................................................................................51 
18. 
REFERENCES ...........................................................................................................52 
19. 
APPENDICES ............................................................................................................53 
 
 


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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................15 
Table 2: 
Schedule of Assessments ............................................................................................21 
Table 3: 
Investigational Product ...............................................................................................27 
Table 4: 
Study Medication Interruption Criteria ......................................................................29 
Table 5: 
Physician’s Global Assessment ..................................................................................32 
Table 6: 
Area Score ..................................................................................................................33 
Table 7: 
Severity Score .............................................................................................................33 
Table 8: 
Four signs of AD used to calculate EASI severity score ............................................34 
 
 
  


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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
AST 
Aspartate aminotransferase 
AV 
Atrioventricular 
BCC 
Basil cell carcinoma 
BID 
Twice a day 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
CBC 
Complete blood count 
CRAs 
Clinical research associates 
CS 
Clinically significant 
DMSO 
Dimethylsulfoxide 
EASI 
Eczema Area and Severity Index 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HCV 
Hepatitis C Vaccine 
HDL 
High-density lipoprotein 
HIV 
Human immunodeficiency virus 
ICH 
International Conference on Harmonization 
IC50 
Half maximal inhibitory concentration 
IRB 
Institutional Review Board 
JAK1 
Janus kinase 1 
JAK2 
Janus kinase 2 
JAK3 
Janus kinase 3 


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Abbreviation or Specialist Term 
Explanation 
LDH 
Lactate dehydrogenase 
LDL 
Low-density lipoproteins 
PEG400 
Polyethylene glycol 400 
PGA 
Physician Global Assessment 
PI 
Principal Investigator 
SAD 
Signs of Atopic Dermatitis 
SAE 
Serious adverse event 
SCC 
Squamous cell carcinoma 
SI 
Subject Identifier 
SN 
Subject Number 
SOPs 
Standard operating procedures 
SPA 
Subjects Pruritis Assessment 
sAG 
Surface antigen 
TSLP 
Thymic stromal lymphopoietin 
TyK2 
Tyrosine kinase 2 
ULN 
Upper Limit of Normal 
WOCBP 
Woman of child bearing potential 
WBC 
White blood cell  


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5. 
INTRODUCTION 
Aclaris Therapeutics, Inc. is developing ATI-502 Topical Solution for the treatment of stable 
patchy alopecia areata, vitiligo, androgenetic alopecia and atopic dermatitis.  ATI-502 is a potent 
highly selective inhibitor of Janus kinase 1 (JAK1) and Janus kinase 3 (JAK3). 
5.1. 
Overview of Atopic Dermatitis 
Atopic dermatitis or eczema is an inflammatory skin disorder characterized by dry, cracked, 
pruritic skin lesions that most often develops in childhood.  Sixty percent of the reported cases 
develop within the first year of life and 85% of the cases develop by the age of 5 (Weston, 2017).   
The disorder often follows a pattern of spontaneous remission with intermittent flares of the 
disease and often continues into adulthood.  The symptoms can range from mild to severe and 
can interfere with daily activities. While the disease is not a life-threatening illness, atopic 
dermatitis can significantly impact a patient’s quality of life.  In patients with moderate to severe 
disease the symptoms rarely clear without treatment.  There are a number of topical treatment 
options including corticosteroids, calcineurin inhibitors, antihistamines, and antimicrobial agents 
that are used to treat atopic dermatitis however it has been over 15 years since a new topical 
therapy with a new mechanism of action has been approved.   
5.2. 
Rationale for the use of ATI-502 in Atopic Dermatitis 
The pathogenesis and etiology of atopic dermatitis (AD) is not completely understood as AD is a 
multifactorial disease developing from complex interactions between genetic, environmental and 
immunological factors (Bissonnette, 2016).  Basic and translational research studies have 
identified several pathogenic pathways that promote atopic dermatitis.  These studies have 
established that the pathogenesis of atopic dermatitis is complex.  It involves a genetic 
predisposition to an impaired epidermal barrier, a key Th2-domiated immune response 
(interferon-γ; IFN-γ), immune changes beyond Th2 associated with IL-22, IL4/IL21, and TSLP 
(thymic stromal lymphopoietin), as well as Th2 allergens (e.g. pollen, house dust mites), 
microbial allergens and self-antigens(Eyerich, 2013). One commonality among the immune 
pathways is pivotal signaling through Janus kinases (JAKs):  IFN-γ (JAK1/2); TSLP (JAK1/2); 
IL-22 (JAK1/TYK2); and IL-4/IL-21 (JAK1/3).  Inhibition of the immune components of atopic 
dermatitis via JAK inhibition has become a leading candidate for a clinical treatment strategy 
(Alves, 2016).  Initial clinical studies have confirmed the potential for both oral and topical 
treatment of atopic dermatitis with JAK inhibitors.   
ATI-502 is a JAK1/3 inhibitor with enzyme IC50 activities of 2nM and 36nM against JAK1 and 
JAK3, respectively.  At a cellular/physiologic level, ATI-502 inhibits interferon-γ-induced 
pSTAT1 activation with an IC50 of 38nM.  The anticipated IC90 concentration is approximately 
0.4µM.  To expect ATI-502 to inhibit JAK1/3 mediated signaling, a significant excess of the 
inhibitor must be present in the target tissue.  Based upon human skin permeation studies (Franz 
chamber with human skin) using the 0.46% ATI-502 formulation, ATI-502 concentrations in 
were extrapolated to be in range of 10-20µM in the dermis and epidermis.  A 10µM 
concentration, combined with anticipated drug gradients, is anticipated to deliver sufficient drug 
to the epidermis and dermis to achieve tissue levels sufficient to inhibit JAK1/3 signaling and 
thereby, diminish immune mediated inflammation (Levy, 2015)(Bissonnette, 2016).   
 


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6. 
TRIAL OUTCOME MEAURES AND PURPOSE 
6.1. 
Primary Outcome Measure 
The primary outcome measure for this study is to assess the safety and tolerability of ATI-502 
Topical Solution, 0.46% in subjects with moderate to severe atopic dermatitis.   
6.2. 
Secondary Outcome Measures 
The secondary outcome measures for this study are to assess the following: 
• Change from baseline in Physician Global Assessment (PGA) score following 4 
weeks of treatment with ATI-502 Topical Solution, 0.46% 
• Change from baseline in body surface area affected by atopic dermatitis following 4 
weeks of treatment with ATI-502 Topical Solution, 0.46%. 
• Change from baseline in Eczema Area and Severity Index (EASI) score following 4 
weeks of treatment with ATI-502 Topical Solution, 0.46%.  
• Change from baseline in the subjects Signs of Atopic Dermatitis (SAD) assessment 
following 4 weeks of treatment with ATI-502 Topical Solution, 0.46%. 
• Change from baseline in Subjects Pruritis Assessment (SPA) score following 4 weeks 
of treatment with ATI-502 Topical Solution, 0.46%. 
 


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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
This is an open label, multicenter, phase 2a study designed to evaluate the safety and tolerability 
of ATI-502 Topical Solution, 0.46% in male and female subjects with a diagnosis of AD as 
defined by the Hanifin and Rajka criteria.  Based on the 5-point Physician’s Global Assessment 
(PGA) scale, subjects must have a score of 3 (moderate) or 4 (severe).  Subjects will be required 
to apply ATI-502 study medication to their identified AD treatment areas twice a day (BID) for a 
total of 4 weeks.  Subjects will be allowed to treat new disease areas with ATI-502 Topical 
Solution, 0.46% if they appear after Visit 2.  All subjects will be required to complete a safety 
follow up visit 4 weeks post last study medication application.     
A total of 30 evaluable subjects who are ≥ 18 years of age with a clinical diagnosis of moderate 
or severe AD will be enrolled to the study.     
Subjects will be required to complete the following treatment visits: 
 
 
Visit 1:  Screening and Photographs for Study Entry Approval 
 
 
Visit 2:  Study Enrollment and First Treatment with Study Medication 
 
 
Visit 3:  Follow up Visit 
 
 
Visit 4:  Follow up Visit 
 
 
Visit 5:  Follow up Visit 
 
 
Visit 6:  End of Study Visit 
7.2. 
Number of Subjects 
A total of 30 evaluable subjects will be enrolled to the study at approximately 6 US 
investigational sites.    
7.3. 
Duration of Treatment 
The anticipated time for study enrollment is 6 months. The duration of the screening period 
could be up to 14 days.  Once a subject is enrolled, the maximum duration of study treatment is 
63 days (56 days plus a 7-day window).   
7.4. 
Treatment Assignment 
This is an open label study. All subjects will be treated twice daily for 4 weeks with ATI-502 
Topical Solution, 0.46%.   
7.5. 
Enrollment Procedures 
Prior to a subject being allowed to enroll to the study, investigational sites will be required to 
submit the subject’s baseline photographs to Canfield Scientific’s database.  Once the photos are 
received into the database a panel of three board certified dermatologists will review the baseline 
photographs.  The panel will review and approve within 24 hours of receipt of the photographs 
into the Canfield imaging database. In cases where the photographs do not properly characterize 


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the disease (due to flashback and whitening on the photographs) the subjects will be allowed to 
enroll to the study based upon the Principal Investigator’s clinical assessment of the subject.   .   
7.6. 
Subject Identifiers 
 
The Investigator will assign a unique five-digit subject identifier (SI) to each subject at Screening 
(Visit 1).  
The SI format will be NN-NNN, using leading zeroes as appropriate, where: 
• The first 2 digits are the investigational site number assigned by Aclaris 
• The final 3 digits are the subject number (SN), assigned in ascending numerical order by 
the Investigator or designee, without omitting or repeating any number, starting with 001.  
For example, the SI for the twenty-third subject that signs an informed consent form at site 
number 01 would be 01-023. The subject will be identified using the SI in all study 
documentation for the duration of the study. 
7.7. 
Replacement of Subjects 
Enrolled subjects that do not complete all visits will be replaced to ensure that 30 evaluable 
subjects complete the study.   
7.8. 
Criteria for Study Termination 
This study may be terminated prematurely in whole or in part due to a change in the benefit/risk 
profile for ATI-502 Topical Solution such that continuation of the study would not be justified 
on medical or ethical grounds.  This determination may be made by the Study Investigators in 
conjunction with the Sponsor, or by the Institutional Review Board (IRB) or the U.S. Food and 
Drug Administration (FDA).  The Sponsor may also elect to terminate the study if enrollment is 
sufficiently slow to prevent the completion of the study in an acceptable timeframe, or if ATI-
502 development is discontinued. 
If the study is terminated prematurely, the Sponsor will notify the Study Investigators and the 
FDA. The Investigator must promptly notify all enrolled subjects and the IRB of study 
termination. 


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8. 
STUDY PROCEDURES 
Table 2 provides a summary of all study specific assessments that are required for this protocol.    
Table 2: 
Schedule of Assessments 
 
Screening 
Baseline 
Treatment 
Post Treatment 
Safety Follow up 
Visit13 
Visit 1 
Visit 2 
 
Visit 3 
Visit 4 
 
Visit 5 
 
Visit 6 
 
Week 
 
0 
1 
2 
4 
8 
Treatment Day 
-14 to 0 
1 
8 
15 
29 
56 
Treatment Window(days) 
N/A 
N/A 
± 3 
± 3 
± 3 
+7 
Informed consent1 
▲ 
 
 
 
 
 
Inclusion/exclusion criteria  
▲ 
▲ 
 
 
 
 
Physical exam2 
▲ 
 
 
 
 
▲ 
Demographics & Medical History 
▲ 
 
 
 
 
 
Vital Signs3 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Fitzpatrick Skin Type 
▲ 
 
 
 
 
 
Atopic Dermatitis History 4 
▲ 
 
 
 
 
 
Clinical Chemistry and CBC5 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
QuantiFERON Gold6 
▲ 
 
 
 
 
 
Virology [HepB (HBsAg), HCV (antibody), HIV 
(antibody)] 
▲7 
 
 
 
 
 
Serum Pregnancy 
▲ 
 
 
 
 
 
Urine Pregnancy 
 
▲ 
 
 
 
▲ 
ECG 
▲ 
 
▲ 
▲ 
▲ 
▲ 
Physician’s Global Assessment (PGA) 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Body Surface Areas Assessment 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Identification of AD Treatment Area 
▲ 
▲ 
 
 
 
 
Eczema Area and Severity Index (EASI) 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Subjects Pruritis Assessment (SPA) 
 
▲ 
▲ 
▲ 
▲ 
▲ 
Signs of Atopic Dermatitis (SAD) 
 
▲ 
▲ 
▲ 
▲ 
▲ 
Standardized Photography8 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Dispensing of study medication9 
 
▲ 
▲ 
▲ 
 
 
Treatment with ATI-502 
 
▲10 
▲ 
▲ 
▲ 
 
Subject Instructions11 
▲ 
▲ 
▲ 
▲ 
▲ 
 
Concomitant medications/therapies 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Adverse Events12 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
1A written, signed ICF must be obtained from each subject prior to performing any study related procedure 


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2 A physical exam includes: general appearance, examination of head, eyes, ears, nose and throat, extremities, respiratory, cardiovascular, abdominal, neurological, 
musculoskeletal, lymphatic and skin assessment. 
3 Vital signs include: oral or ear temperature, blood pressure, heart rate, respiration rate (height and weight at baseline only). 
4 Prior therapies or treatments a subject received to treat AD must be documented for each subject.   
5 Serum chemistry panel to include:  albumin, alkaline phosphatase, ALT, AST, BUN, bicarbonate, calcium, chloride, creatinine, glucose, lactate dehydrogenase (LDH), 
phosphorus, potassium, sodium, total bilirubin, total protein, uric acid, total cholesterol, LDL, HDL triglycerides, and complete blood count including differential.    
6 All subjects must have a blood sample drawn to test for the tuberculosis virus (QuantiFERON Gold).  The blood sample will be sent to a central laboratory for analysis 
and results must be received prior to enrolling the subject.   
7 All subjects will be required to have virology testing for HepB (HBsAG), HCV(antibody), and HIV (antibody).  If a subject demonstrates to have 
serological evidence HepB (HBsAG), HCV (antibody) or HIV (antibody), the subject will not be allowed to enroll to the study.  
8Canfield staff will review all photographs within 2 days of the photographs being submitted.  If a re-take is required, Canfield will notify the site and the 
re-take photographs will need to be performed within 7 days of the visit. Prior to enrollment to the study, each subject’s Visit 1 photos will be reviewed 
by a panel of board certified dermatologists to ensure that the subject’s target areas for treatment meet the study entry criteria.  In cases where the 
photographs do not properly characterize the disease (due to flashback and whitening on the photographs) the subjects will be allowed to enroll to the 
study based upon the Principal Investigator’s clinical assessment of the subject.     
9At visit 2, following confirmation that the subject is approved for enrollment to the study, the site will weigh and dispense supplies of ATI-502 study 
medication and disposable droppers to the subject for at home application of the study medication.  
10 All subjects will have their first application of study medication applied in the clinic during Visit 2.  Subjects will continue to apply ATI-502 Topical 
Solution, 0.46% to all target areas twice a day for 4 weeks (Day 28) unless the subject meets the criteria for treatment interruption.  If new areas of AD 
develop, subjects will be allowed to treat these areas with the ATI-502 study medication.  
11Sites will be required to review with each subject the proper application of the study medication and remind that they must refrain from exercise that 
may cause excessive sweating, bathing or swimming for a period of 6 hours after the application of study medication. Subjects are also to be reminded 
that they may not apply moisturizers, emollients, or sunscreen to target AD areas during protocol treatment.     
12 All non-serious AEs will be collected from the time of first study medication application until the final study visit.  Serious AEs will be collected from 
the time of consent through the final study visit.   
13A final safety follow up visit will be conducted at week 8 (Visit 6).  For those subjects that discontinue the study early, they must return to the clinic 4 
weeks following the last study medication application for a final safety visit.   
 


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9. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
9.1. 
Subject Inclusion Criteria 
Subjects must meet the following criteria to be eligible for participation in the study: 
1. Able to comprehend and willing to sign an Informed Consent Form (ICF). 
2. Male or non-pregnant, non-nursing female subjects ≥ 18 years old at the time of informed 
consent. 
3. Subject must have diagnosis of AD according to the Hanifin and Rajka criteria. 
4. Subject must have a diagnosis of moderate (PGA =3) or severe (PGA=4) AD for a period 
of ≥6 months prior to the first dose of study medication (Visit 2).   
5. Subject Visit 1 photographs are approved for enrollment by the dermatology review 
panel. 
6. Body surface area involvement must be between 2-20% (excluding scalp, face, palms of 
hands, soles of feet, groin and genitalia). 
7. Subject must have an absolute neutrophil count (ANC) and a platelet count within normal 
limits 
8. Subject must be willing to refrain from washing area of treatment or swimming for 6 
hours after each treatment application with ATI-502. 
9. Subjects must be willing to refrain from excess of sun exposure.   
10. Subject is willing and able to follow all study instructions and be willing to attend all 
study visits.   
11. Subject must refrain from participating in strenuous exercise that would cause profuse 
sweating for a period of 6 hours after each treatment application with ATI-502.   
12. Subject must refrain from using moisturizers, emollients, and sunscreen on target AD 
treatment area for the duration of protocol therapy.   
13. Be in good general health and free of any known disease state or physical condition 
which, in the investigator’s opinion, might impair evaluation of the subject or which 
might expose the subject to an unacceptable risk by study participation. 
14. If a woman of childbearing potential (WOCBP), must have a negative serum pregnancy 
test at Screening (Visit 1) and a negative urine pregnancy test at Baseline (Visit 2) and 
agree to: use a highly effective method of birth control for the duration of the study; not 
be planning a pregnancy during the study duration and use contraception for 30 days after 
last application of study medication. 
15. Sexually active male subjects must agree to use a barrier method of contraception from 
the first application of study medication to at least 30 days after the last application of 
study medication. 


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9.2. 
Subject Exclusion Criteria 
1. Subject has any signs or symptoms associated with AD therapy (e.g., history of 
anaphylaxis, hypersensitivity reactions, skin atrophy, striae, pigmentary changes) which, 
in the investigator’s opinion, might impair evaluation of the AD or which exposes the 
subject to unacceptable risk by study participation.   
2. Subjects unable to complete the following required washout periods: 
• Phototherapy within 4 weeks prior to Visit 1.   
• Systemic immunosuppressant or immunomodulatory therapy (e.g. etanercept, 
alefacept, infliximab, methotrexate) within 16 weeks prior to Visit 1. 
• JAK inhibitors (systemic and topical) within 4 weeks prior to Visit 1. 
• Systemic corticosteroids (intranasal and inhaled corticosteroids are allowed) within 4 
weeks prior to Visit 1.  
• Cytostatic agents within 4 weeks prior to Visit 1. 
• Crisaborole within 2 weeks prior to Visit 1.   
• Dupilumab or other monoclonal antibody within 3 months prior to Visit 1. 
• Systemic antibiotics with 2 weeks prior to Visit 1. 
• Topical treatments for atopic dermatitis (corticosteroids, calcineurin inhibitors, 
topical H1 and H2 antihistamines, topical antimicrobials, and other medicated topical 
agents) within 1 week prior to Visit 1.   
• Live attenuated vaccine treatment within 12 weeks prior to Visit1.   
3. Use of prescription moisturizers within 7 days of Visit 1.    
4. Subject has used any emollients/moisturizers on the planned treatment area (s) within 4 
hours of Visit 1.   
5. Subject has clinically infected AD.  
6. Subject is currently using an oral H1 antihistamines (e.g. diphenhydramine, terfenadine) 
UNLESS the subject is on a stable dose for at least 14 days prior to Visit 1.  
7. Clinically significant laboratory abnormalities at Visit 1 that, in the opinion of the 
Investigator, would make the subject a poor candidate for the study 
8. History of, or current, severe, progressive or uncontrolled renal, hepatic, gastrointestinal, 
pulmonary, cardiovascular, genitourinary (renal disease) or hematological disease, 
neurologic or cerebral disorders, infectious disease or coagulation disorders that, as 
determined by the Investigator, would preclude participation in and completion of study 
assessments. 
9. History of, current or suspected systemic or cutaneous malignancy and /or 
lymphoproliferative disease, other than subjects with: a history of adequately treated and 
well healed and completely cleared non-melanoma skin cancers (basal or squamous cell 
carcinoma) treated successfully at least 1 year prior to study entry with no evidence of 
disease. 


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10. Evidence of active or latent bacterial (including tuberculosis) or viral infections at the 
time of enrollment or history of incompletely treated or untreated tuberculosis.  Subjects 
who have completed therapy for latent tuberculosis may participate. 
11. History of a serious local infection (e.g., cellulitis, abscess) or systemic infection 
including but not limited to a history of treated infection (e.g., pneumonia, septicemia) 
within 3 months prior to Visit 2. Subjects on an antibiotic for a non-serious, acute local 
infection must complete the course prior to enrollment into the study. 
12. Positive serological test for HIV(antibody), HCV (antibody), or HepB (HBsAg).      
13. Subjects with herpes zoster or cytomegalovirus (CMV) that resolved less than 2 months 
before study enrollment. Subjects with a history of frequent outbreaks of Herpes Simplex 
Virus (defined as 4 or more outbreaks a year). 
14.   Screening ECG findings of: 
a. QTcF >450msec for males or >470msec for females (use of the ECG algorithm is 
acceptable for this purpose) 
b. Resting heart rate ≤ 45 or Heart Rate ≥ 100 beats/minutes if considered to be caused 
by a clinically significant pathology.  The investigator may enter a patient with a HR 
outside of these values if considered to have no clinical significance. 
c. Rhythm disturbance other than sinus arrhythmia or ectopic supraventricular rhythm 
(ectopic atrial rhythm) 
d. Conduction disturbance including PR >240msec, pre-excitation (delta wave and PR 
<120msec), second degree or higher AV block 
e. Acute or chronic signs of ischemia  
f. Left Bundle Branch Block 
g. Prior myocardial infarction 
15. Subject has participated in an investigational drug trial within 30 days prior to Visit 1.   
9.3. 
Subject Withdrawal Criteria 
Subjects will be informed that they are free to withdraw from the study at any time and for any 
reason. 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 
criteria, occurrence of AEs, occurrence of pregnancy, use of a prohibited therapy or subject is 
unwilling or refuses to continue with the protocol defined procedures, treatments and/or study 
visits and/or subject withdraws consent. 
The date the subject is withdrawn from the study and the reason for discontinuation must be 
recorded in the subject’s electronic case report forms (eCRFs). All withdrawn subjects will be 
required to complete one last safety follow up visit approximately 30 days after last study 
medication application.  If the subject withdrawals their consent to have this visit completed this 
needs to be appropriately documented in the subject’s source notes and on the subject’s eCRF.   
 
Subjects will be permanently discontinued from the study in the event of any of the following: 
• Severe infection requiring parental antimicrobial therapy or hospitalization 
• Symptomatic herpes zoster 


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• Malignancy – except for non-melanoma skin cancer (SCC or BCC) not in or near the 
treatment area 
• Anaphylactic or severe allergic reaction 
• WBC Count:  < 1 x 109/L or second occurrence of < 2 x 109/L 
• ANC:  
< 0.5 x 109/L or second occurrence of < 1 x 109/L 
 
• Lymphocyte count: 
< 0.3 x 109/L or second occurrence of < 0.5 x 109/L  
  
• Platelet count:  
< 50 x 109/L or second event of < 75 x 109/L - in each case, value should 
be confirmed by retesting before treatment discontinuation 
• Hemoglobin:   
< 6.5 g/dL or second occurrence of < 8 g/dL - in each case, value should 
be confirmed by retesting before treatment discontinuation 
• AST or ALT:  
o > 5 x ULN persisting for 2 weeks of study medication interruption or second 
event of > 5 x ULN 
o 3 x ULN with total bilirubin >2 x ULN or symptoms of hepatocellular  
injury [fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, 
rash and/ or eosinophilia (>5%)].  
 
• Any subject who develops any of the following ECG findings during the active treatment 
phase will be instructed to stop study medication and will be withdrawn from the study: 
 
o Clinically significant rhythm disturbance other than sinus rhythm or ectopic 
supraventricular rhythm (ectopic atrial rhythm) 
o Clinically significant conduction disturbance including PR >240msec, pre-
excitation (delta wave and PR <120msec), second degree or higher AV block  
o New finding of QRS>120ms (if not present at screen.  For example, subjects with 
Right Bundle Branch Block at screening would not need to be withdrawn from the 
study if their subsequent ECGs remained unchanged). 
o Evidence of QT-interval prolongation, defined as an increase in the QTcF 
interval>60ms from Visit 1 
o Acute signs of ischemia or infarction 
o Any ECG abnormality which may, in the opinion of the investigator, represent a 
new medical issue of concern 
 
A subject that experiences any of the above events must be discontinued from study medication 
treatment, the site staff must inform the Aclaris medical monitor of the event, and the site staff 
must perform protocol-required procedures for trial discontinuation and follow-up.    
 
 
 


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10. 
STUDY MEDICATION AND MANAGEMENT 
10.1. 
Description of Study Drug 
The study medication for this study is ATI-502 Topical Solution, 0.46%.  It is a clear, colorless 
to light pink solution.  The inactive ingredients include: purified water, transcutol P, propylene 
glycol, PEG400, dimethyl sulfoxide (DMSO), kolliphor CS 20, benzyl alcohol, poloxamer 188, 
and povidone K30. 
Table 3: 
Investigational Product 
STUDY MEDICATION INFORMATION 
Study medication name 
ATI-502 
Dosage Strength 
0.46% 
Manufacturer 
PMRS, Inc., Horsham, PA 
Pharmaceutical Form 
Topical Solution 
Container 
Amber Glass Bottle, 120 mL with screw cap  
Storage Conditions 
59°F to 77°F (15°C to 25°C)  
Dose regimen 
Route 
Topical 
Frequency 
Twice-daily 
Duration of administration 
4 weeks 
Other supplies 
Disposable, single-use droppers will be provided. 
10.2. 
Subject Randomization 
This is an open label study therefore, no randomization schema will be generated for this study.  
All subjects will receive open label ATI-502 Topical Solution, 0.46%.  
10.3. 
Study Drug Packaging, Labeling and Storage 
The study medication must be used by the study subjects only.  Investigational site staff will 
explain the application of the study medication to subjects. 
Study medication will be provided by Aclaris Therapeutics, Inc. and labeled according to 
regulatory requirements.  Study medications must be stored in a secure area with limited access 
under appropriately controlled and monitored storage conditions.  Study medication should be 
stored at controlled room temperature 59°F - 77°F (15°C – 25°C).  Subjects will be instructed to 
store the study medication in the original glass bottle (in the carton provided) at room 
temperature, away from heat, moisture, direct light, and to keep it from freezing and out of the 
reach of children. 
The study medication will be supplied in amber glass 120 mL bottles.  Disposable droppers with 
1 mL calibration mark will be provided to the investigational sites for dispensing to enrolled 
subjects.   
Study drug for this study is ATI-502 Topical Solution 0.46%.  The study medication will be 
supplied to subjects enrolled to the study at Visit 2.     


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10.4. 
Study Drug Accountability and Disposal 
The Principal Investigator or designee is responsible for ensuring accountability for the 
investigational agent, including reconciliation of medications and maintenance of medication 
records.  Upon receipt of study medication, the clinical site will check for accurate delivery and 
acknowledge receipt by signing (or initialing) and dating the documentation provided.  One copy 
of this document will be returned to Aclaris Therapeutics, Inc. (or designee) and one copy will be 
maintained in the study file at the site. In addition, an accurate study medication disposition 
record will be kept, specifying the amount dispensed for each subject and the date of dispensing. 
This inventory record will be available for inspection at any time. At the completion of the study, 
the original inventory record will be available for review by Aclaris Therapeutics, Inc. upon 
request.  Final medication accountability will be performed by the study monitor at the 
completion of the study and all used and unused study medication bottles will be returned to 
Aclaris Therapeutics, Inc. or designee for disposal. 
10.5. 
Additional Clinical Supplies 
In addition to the study medication supplies, each site will be supplied with the following clinical 
supplies to conduct the study: 
• Disposable study medication dispensing droppers 
• Insulated bags for subjects to transport study medication supplies 
• Canfield photography equipment 
• Central laboratory testing kits 


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11. 
TREATMENT OF SUBJECTS 
11.1. 
Identification of Target Treatment Area 
At Visit 1 and Visit 2, the investigator will identify a target treatment area(s) that meets all 
inclusion criteria (e.g. a diagnosis of AD based on the criteria of Hanifin and Rajka, BSA 
between 2-20%, and a PGA score of 3 or 4).  The target treatment area can not include the scalp, 
face, palms of hands, soles of feet, groin or genitalia.  The investigator will record the identified 
target treatment area on the body map in the subject’s source documents and eCRF.  These target 
treatment areas will be photographed at each specified protocol time point (Refer to Table 2).  
Sites will use colored stickers to mark the treatment areas prior to the photographs being taken.  
(Refer to Section 12.6 for photography instructions) 
If new areas of atopic dermatitis develop while the subject is on study, these areas may be treated 
with the ATI-502 study medication (excluding the face, scalp, soles of feet and palms of hands).  
The treating investigator must identify these new treatment areas at a treatment visit (Visit 2, 3 or 
4) to ensure that the area meets the protocol defined treatment criteria.  These new treatment 
areas will be documented in the subject’s source documents and in the eCRF.   
11.2. 
Application of Investigational Product 
Subjects will be instructed to apply a thin film of ATI-502 Topical Solution 0.46%, twice-daily -
once in the morning and approximately 8-12 hours later - to the identified target AD areas.  The 
ATI-502 study medication should be applied to clean dry skin.  The subject must wash her/his 
hands thoroughly before and after each study drug application.  If new areas of AD develop 
while the subject is on study, ATI-502 study medication may be applied to these sites.   
Investigational site staff will dispense 2 bottles of study medication along with disposable 
droppers to the subject Visit 2. Subsequent study drug dispensing will be determined by the site 
based on the amount used between visits.  Study medication bottles will be weighed by the site 
staff at the time of dispensing and when the bottles are returned.  Subjects are to return used and 
unused study medication at each study visit so that the bottles can be weighed.  Sites can re-
dispense partially used bottles of study medication at a visit. The disposable droppers should be 
disposed of at the subject’s home. 
11.3. 
Study Medication Interruption 
Treatment with ATI-502 Topical Solution, 0.46% should be temporarily interrupted in the event 
of severe adverse events considered related to ATI-502 Topical Solution, 0.46%, or in the event 
of one or more of the abnormal laboratory values in Table 4. 
Table 4: 
Study Medication Interruption Criteria 
Laboratory Test 
Hold Study Medication if: 
Resume Study Medication if: 
WBC count 
< 2 x 109/L 
≥ 2.5 x 109/L 
ANC 
< 1 x 109/L 
≥ 1.5 x 109/L 
Lymphocyte count < 0.5 x 109/L 
≥ 0.75 x 109/L  
Platelet count 
< 75 x 109/L 
≥ 100 x 109/L 


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Hemoglobin 
< 8 g/dL or a decrease > 2g/dL 
≥ 10 g/dL 
AST or ALT 
> 3 x ULN 
< 2 x ULN or within 20% of Baseline values 
Serum creatinine 
>2 x ULN 
<1.5 x ULN or within 10% of Baseline value 
If a subject has one or more of the abnormal laboratory values noted in Table 4, the investigator 
or designee upon receipt and review of the central laboratory report should instruct the subject to 
hold study medication applications. The investigator or designee should ask the subject about 
symptoms, concomitant illnesses and medications and repeat the test(s) as soon as possible.  The 
Medical Monitor must be notified of dose interruptions due to SAEs considered related to study 
medication or laboratory abnormalities noted in Table 4. 
If the retest confirms the abnormal laboratory value, then the study medication should continue 
to be held followed by repeat testing once a week or sooner at the discretion of the investigator.  
The subject should be followed until the laboratory abnormality(s) returns to normal or to 
baseline values. 
11.4. 
Skin Care while on Study 
Prior to the application of the ATI-502 study medication, the identified AD treatment area should 
be washed and cleaned using the subject’s routine cleansing products.  The area should be dried 
completely prior to the application of the study medication.  Subjects must not wash the 
treatment area, go swimming or perform physical exercise that may cause perfuse sweating for a 
period of 6 hours after applying the ATI-502 study medication.  While on study, subjects should 
continue to use their routine cleansing and cosmetic products on study.    
Subjects may not use a non-therapeutic, bland emollient/moisturizer or sunscreens on the AD 
target treatment area for the duration of the study.  Moisturizers, emollients, and sunscreens may 
be used on NON-AD target treatment areas.  Subjects must take special precautions to try and 
limit sun exposure to all identified treatment areas by wearing protective clothing and applying 
sunscreen to NON -AD target treatment areas only.   
11.5. 
Concomitant Medications 
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). 


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11.6. 
Prohibited Medications 
While subjects are participating in this study they are prohibited from using the following 
medication/therapies: 
• Phototherapy -Subjects must refrain from excessive sunlight (natural or artificial) and 
must apply sunscreen to all treatment areas if excessive exposure cannot be avoided.     
• Systemic immunosuppressant or immunomodulatory therapy (e.g. etanercept, 
alefacept, infliximab, methotrexate)  
• JAK inhibitors (systemic or topical) 
• Systemic corticosteroids (intranasal and inhaled corticosteroids are allowed)  
• Cytostatic agents  
• Crisaborole 
• Dupilumab or other monoclonal antibody for the treatment of AD 
• Systemic antibiotics  
• Topical treatments for atopic dermatitis (corticosteroids, calcineurin inhibitors, 
topical H1 and H2 antihistamines, topical antimicrobials, and other medicated topical 
agents)  
• Prescription moisturizers 
• Topical antibacterial medications or products, including soaps, bleach baths, or 
topical sodium hypochlorite-based products. 
• Vaccine treatments 
11.7. 
Treatment Compliance 
The investigator or designee will be responsible for monitoring subject compliance through 
questioning the subject, documenting missed doses, if any, weighing the bottle before dispensing 
and after return and visual inspection of the quantity in the study medication bottles (used and 
unused).  Study staff will counsel the subjects, as required to make sure subjects are compliant 
with study medication applications. 
 


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12. 
STUDY ASSESSMENTS 
12.1. 
Physician’s Global Assessment (PGA) 
The PGA is the investigator’s assessment of the average overall severity of subject’s AD at a 
particular point in time.  At every study visit, the investigator will assess the PGA using the scale 
below and report the one integer that best describes the average overall severity of each target 
evaluation area of AD per subject.  One assessment will be conducted for each target treatment 
area. 
Table 5: 
Physician’s Global Assessment 
PHYSICIAN’S GLOBAL ASSESSMENT 
Grade 
Descriptor 
0 
Clear: No erythema or induration; no oozing/crusting; barely perceptible 
residual post-inflammatory hypo- or hyperpigmentation may be present 
1 
Almost Clear: Minimal light red erythema and/or induration; no 
oozing/crusting 
2 
Mild: Light red erythema with mild induration; no oozing/crusting 
3 
Moderate: Red erythema with moderate induration; oozing/crusting may be 
present 
4 
Severe: Bright or deep red erythema with severe induration; 
oozing/crusting present 
 
12.2. 
Body Surface Area (BSA) 
For this study, 1% Body Surface Area (BSA) is defined as the area of the subject’s hand with 
the fingers and thumb together. The subjects are required to have 2-20% total BSA of active AD 
to be enrolled in the study.  Body surface area of each target treatment area will be assessed at 
each treatment visit.  If new areas of AD develop while the subject is on study, these new areas 
will not be assessed.   
12.3. 
Eczema Area and Severity Index (EASI) 
Investigators will use the EASI to assess each subject’s extent and severity of atopic dermatitis at 
Visit 1 and then at every protocol defined treatment visit.   
The EASI divides the subject’s body down into four body regions: 
• Head and Neck 
− Face occupies 33% (17% each side), neck 33% (17% front and back) and scalp 
33% of the head and neck region 
• Trunk (including genital areas) 
− Front occupies 55% and back 45% of the trunk 
• Upper limbs 


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− Each arm occupies 50% of the upper limbs region (front or back of one arm is 
25%) 
• Lower limbs (including buttocks) 
− Each leg occupies 45% (front or back of one leg is 22.5%) and buttocks 10% of 
the lower limbs region 
An area score is recorded for each of the four regions of the body.  The area score is the 
percentage of skin affected by AD for each body region. 
Table 6: 
Area Score 
Area Score 
Percentage of skin affected by AD in each region 
0 
No active AD in this region 
1 
1-9% 
2 
10-29% 
3 
30-49% 
4 
50-69% 
5 
70-89% 
6 
90-100%; the entire region is affected by AD 
The severity score is recorded for each of the four regions of the body.  The severity score is the 
sum of the intensity scores for four signs.  The four signs are: 
• Redness (erythema, inflammation) 
• Thickness (induration, papulation, swelling-acute AD) 
• Scratching (excoriation) 
• Lichenification (lined skin, furrowing, prurigo nodules-chronic AD) 
The AVERAGE intensity of each sign in each body area is assessed according to the following 
table: 
Table 7: 
Severity Score 
Score 
Intensity of redness, thickness/swelling, scratching, lichenification 
0 
None, absent 
1 
Mild (just perceptible) 
2 
Moderate (obvious) 
3 
Severe 
Half scores are allowed.  In darker skin type subject’s, it may be difficult to assess redness and in 
this case increase the average redness score by 1 level.   


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Table 8: 
Four signs of AD used to calculate EASI severity score 
Intensity 
None 
Mild 
Moderate 
Severe 
Redness 
Score 0 
Score 1 
Score 2 
 
Score 3 
Thickness/induration 
papulation/oedema 
Score 0 
Score 1 
Score 2 
Score 3 
Scratching 
Score 0 
Score 1 
Score 2 
Score 3 
Lichenification/prurigo 
Score 0 
Score 1 
Score 2 
Score 3 
(Hanifin, 2001) 
12.4. 
Signs of Atopic Dermatitis (SAD) 
The Signs of Atopic Dermatitis (SAD) assessment is the investigator’s assessment of the 
average overall severity of signs of AD in each target AD evaluation area at a particular 
time-point. The investigator should NOT refer to any other assessments to assist with these 
assessments. 
At Visits 2 through 6, the investigator will assess the signs of AD using the scales below 
and report the one integer that best describes the average overall severity of each of the 
signs in each target treatment area. Any new areas of AD that develop outside the baseline 
identified target treatment areas will not be assessed by the SAD.  
This assessment must be done at Visit 2 prior to the first study medication application.  This 
assessment must be done at Visits 3-6 either prior to the first study medication application or 
approximately 4 hours after the most recent study medication application. 
 


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ERYTHEMA (REDNESS) 
Grade 
Descriptor 
0 
None: No redness 
1 
Mild: Barely perceptible, light redness 
2 
Moderate: Definite redness, easily detectable 
3 
Severe: Marked, deep/dark red 
 
INDURATION (ELEVATION) 
Grade 
Descriptor 
0 
None: No elevation 
1 
Mild: Barely perceptible elevation, may be more palpable than visually 
perceptible; scattered 
2 
Moderate:  Definite visually perceptible elevation; not 
extensive/moderate coverage 
3 
Severe:  Marked and obvious elevation; extensive presence/significant 
coverage 
 
LICHENIFICATION (EPIDERMAL THICKENING) 
Grade 
Descriptor 
0 
None: No epidermal thickening 
1 
Mild: Minimally perceptible epidermal thickening, skin lines may be 
slightly accentuated 
2 
Moderate: 
Definite 
epidermal 
thickening, 
skin 
lines 
accentuated/pronounced 
3 
Severe: Marked epidermal thickening, skin lines and very pronounced 
 
EXCORIATION (SIGNS OF SCRATCHING) 
Grade 
Descriptor 
0 
None: No skin damage 
1 
Mild: Minimal damage to the top layer of skin, there may be a 
suggestion of linear pattern to the damage 
2 
Moderate: Definite damage/loss of the top layer of the skin with 
perceptible linear pattern 
3 
Severe: Marked damage/loss of the top layer of the skin, pronounced 
linear pattern of damage 
 
OOZING/CRUSTING (EXUDATION) 
Grade 
Descriptor 
0 
None: No oozing or crusting 


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1 
Mild: Barely perceptible oozing, lesions may or may not be moist, no 
crusting 
2 
Moderate: Definite oozing, lesions damp to the touch, crusting may be 
present 
3 
Severe: Marked oozing, lesions are wet, crusting present 
12.5. 
Subjects Pruritis Assessment (SPA) 
The SPA is the subject’s assessment of the worst severity of pruritus, a symptom of AD, in each 
of the target evaluation areas of AD during the 24 hours prior to each follow up visit. The subject 
should NOT refer to any other assessments or any other active areas of AD outside the bilateral 
target evaluation areas to assist with these assessments. 
At Visits 2 through 6, the subject will perform the SPA using the 11-point numeric rating scale 
below and report the one integer that best describes the worst severity of pruritus on each target 
evaluation area (identified at baseline) over the previous 24 hours.   
 
PRURITUS (ITCHING) 
Grade 
Descriptor 
0 
No itch 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Worst possible itch 
 
To complete the SPA, the study coordinator should show the SPA scale to the subject, explain 
the scale and ask the subject to indicate which integer best describes the worst pruritus the subject 
experienced on each target evaluation area of AD over the previous 24 hours.  
This assessment must be done at Visit 2 prior to the first study medication application.  This 
assessment must be done at Visits 3-6 either prior to the first study medication application or 
approximately 4 hours after the most recent study medication application. 
12.6. 
AD Treatment Area Photography 
Canfield Scientific will supply all investigational sites with study specific camera equipment to 
photograph each subject’s identified target AD treatment areas.  Sites will be supplied with color 
stickers to identify each target area.  Details regarding the use of the equipment and how to 
upload the photographs to the Canfield database will be supplied to the sites in a study specific 
Canfield study manual.   


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At Visit 1, investigational sites must identify and photograph the proposed target AD treatment 
areas that will be treated and followed throughout the duration of the study. These standardized 
photographs will be submitted to Canfield and reviewed by a panel of 3 dermatologists prior to 
allowing the subject to be enrolled to the study.  The photographs will be assessed by the panel 
of dermatologists to confirm that the subject meets the protocol defined inclusion in the study. In 
cases where the photographs do not properly characterize the disease (due to flashback and 
whitening on the photographs) the subjects will be allowed to enroll to the study based upon the 
Principal Investigator’s clinical assessment of the subject. 
Sites will be required to photograph each target AD treatment area at all protocol defined 
treatment visits.  
 
 


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13. 
ASSESSMENT OF SAFETY 
13.1. 
Safety Parameters 
Safety will be assessed throughout the study by the investigator or a designated and appropriately 
trained staff member. 
13.1.1. 
Demographic/Medical History 
During the screening visit (Visit 1), the investigator or designee will interview each subject to 
obtain demographic information including date of birth, sex at birth, Fitzpatrick skin type, race 
and, if appropriate, ethnicity. The investigator or designee will interview each subject to obtain 
medical history information related to all medical conditions, surgeries and disease states that, at 
screening: are ongoing, require concomitant therapy or are, in the opinion of the investigator, 
relevant to the subject’s study participation.  In addition, the medical history of women who are 
not of childbearing potential should reflect the reason e.g. post-menopausal for 1 year or greater, 
total hysterectomy.  Information regarding the subject’s prior treatments or therapies related to 
AD must be documented.   
13.1.2. 
Vital Signs 
Vital signs will be measured at each visit during the study. The following items will be 
measured: 
• Body temperature 
• Heart rate 
• Respiration rate 
• Blood pressure (systolic and diastolic) after the subject sits quietly for at least 5 minutes 
• Height (at Visit 2 only) 
• Weight (at Visit 2 only) 
Any measure that is, in the opinion of the investigator, abnormal AND clinically significant (CS) 
must be recorded as history if found prior to the first study medication application, or as an AE if 
found after the first study medication application begins. 
13.1.3. 
Physical Examination 
The investigator or designee will perform a physical examination for all body systems (general 
appearance, examination of head, eyes, ears, nose and throat, respiratory, cardiovascular, 
abdominal, neurological, musculoskeletal, lymphatic and skin assessment) at Screening (Visit 1) 
and end of study (Visit 6). 
13.1.4. 
Electrocardiogram (ECG) 
Standard 12-lead ECGs will be performed by a qualified staff member at Screening (Visit 1), 
Day 8 (Visit 3), Day 15 (Visit 4), Day 29 (Visit 5) and Day 56 (Visit 6/End of Study).  The 
ECGs must be obtained using a standard 12-lead ECG with a 10mm/mV amplitude, at 25mm/sec 
and a 5 to 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.  


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A central cardiology laboratory will provide ECG equipment, supplies and site training.  In 
addition, the central cardiology laboratory will process ECGs received by the sites and report 
results via a secure study portal.  The ECG results will be interpreted by a qualified health 
professional (evaluator) and the interpretation reported either directly on the tracing or in a 
separate report.   The evaluator will interpret the results of every ECG and define the ECG as 
“normal” or “abnormal”.  Variations such as minor ST changes (i.e., <0.5mm depression) and 
early re-polarization are considered normal.  
The investigator must review the evaluator’s interpretation of each subject’s screening ECG prior 
to Visit 2. The investigator will review the evaluator’s interpretation of all ECG reports in a 
timely manner and comment on the clinical relevance of any result that is defined by the 
evaluator as abnormal.  
Any abnormalities that are, in the opinion of the investigator, clinically significant, must be 
reported as history if found prior to the start of the first dose of study medication or as an AE if 
found after the start of the first dose of study medication   
13.1.5. 
Pregnancy Testing 
Subjects who are WOCBP must have a negative serum pregnancy test result at Screening (Visit 
1) to continue in the study, and a negative UPT at Baseline (Visit 2) prior to study entry.  If the 
result of any post-treatment urine pregnancy test is positive, the subject will be withdrawn from 
the study and the subject’s pregnancy documented and followed.  In addition, the investigator or 
designee will perform a urine pregnancy test for subjects who are WOCBP at Visit 6 (Post 
Treatment Safety Follow Up Visit).   
13.1.6. 
Laboratory Assessments 
All subjects are required to have a blood chemistry panel performed at Visit 1 (Screening) and at 
each protocol defined visit.  A qualified staff member will collect non-fasting blood samples and 
ship the samples to a central laboratory for analysis.  The following tests will be performed: 
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 
 


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Uric Acid 
Total cholesterol, LDL, HDL 
 
Triglycerides 
 
13.1.7. 
Virus Serology 
All subjects will be required to have a QuantiFERON TB Gold, HIV, Hepatitis B and HCV 
serological blood test performed at screening.  If the subject demonstrates to have serological 
evidence of any of these viruses, they will not be allowed to enroll to the study.   
13.2. 
Adverse and Serious Adverse Events 
13.2.1. 
Definition of Adverse Events 
13.2.1.1. Adverse Event (AE) 
An AE is the development of an undesirable medical condition or the deterioration of a pre-
existing medical condition following or during exposure to a pharmaceutical product, whether or 
not considered casually related to the product.  In clinical studies, an AE can include an 
undesirable medical condition occurring at any time, including baseline or washout periods, even 
if no study treatment has been administered. 
The investigator should, when certain, report a diagnosis rather than the signs, symptoms or 
clinically significant abnormal laboratory values associated with the AE. Otherwise, signs, 
symptoms or abnormal laboratory values may be used to describe the AE. 
Any CS abnormality discovered prior to the first study medication treatment should be reported 
as medical history, not as an AE. 
All AEs that occur from the time of first study medication application (Visit 2) until 30 days 
after last study medication application must be documented in the subject’s source documents 
and in Aclaris’ EDC system. 
13.2.1.2. Serious Adverse Event (SAE) 
A serious adverse event is an AE occurring during any study phase (i.e., baseline, treatment, 
washout, or follow-up), and at any dose of the investigational product, comparator or placebo, 
that fulfils one or more of the following: 
• Results in death 
• It is immediately life-threatening 
• It requires in-patient hospitalization or prolongation of existing hospitalization 
• It results in persistent or significant disability or incapacity 
• Results in a congenital abnormality or birth defect 
• It is an important medical event that may jeopardize the patient or may require medical 
intervention to prevent one of the outcomes listed above. 


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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 were more 
severe. 
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. 
SAEs will be reported from the time of informed consent until 30 days past last application of 
study medication, whether or not they are related to the study.  SAEs will be documented on the 
Aclaris SAE report form and in the eCRF.    
13.2.1.3. Unexpected adverse events 
An AE is considered unexpected if it is not listed in the Investigator’s Brochure or is not listed at 
the specificity or severity that has been observed. 
13.3. 
Recording of Adverse Events 
13.3.1. 
Adverse event reporting period 
The investigator must start reporting non-serious AEs with the subject’s first study medication 
application and continue reporting until the end of the subject’s last study visit. Reporting for 
SAEs must start when the subject signs the ICF and continue until the end of the subject’s last 
visit. 
13.3.2. 
Severity 
The investigator is to define the severity of each AE using the following definitions as a 
guideline. The investigator will consider the range of the possible severity of the event and 
identify the severity that is the most appropriate according to her/his medical judgment. 
Mild – Awareness of signs or symptom, but easily tolerated. 
Moderate – Discomfort, enough to cause interference with usual activity. 
Severe – Incapacitating with inability to perform usual activity. 
13.3.3. 
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 causal relationship between the study medication and the 
AE. 


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Not Related – There is not a reasonable causal relationship between the study medication 
and the AE. 
The expression “reasonable causal relationship” is meant to convey in general that there are facts 
(evidence) or arguments to suggest a causal relationship (International Conference on 
Harmonization [ICH] E2A). 
13.3.4. 
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?”  If appropriate, based on the subject’s response to non-directed questioning to elicit AEs, 
the investigator will follow-up with directed questions and appropriate evaluations. 
Any AE noted during the reporting period must be reported in the source documents and on the 
appropriate AE eCRF. 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 at 
the subject’s last study visit, until in the opinion of the investigator, the AE reaches a clinically 
stable outcome with or without sequelae. 
Should a pregnancy occur, it must be reported and recorded on Aclaris pregnancy form.  
Pregnancy in itself is not regarded as an AE unless there is a suspicion that an investigational 
product may have interfered with the effectiveness of a contraceptive medication. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth or 
congenital abnormality) must be followed up and documented even if the patient was 
discontinued from the study. 
All reports of congenital abnormalities/birth defects are SAEs.  Spontaneous miscarriages should 
also be reported and handled as SAEs.  Elective abortions without complications should not be 
handled as AEs. 
13.3.5. 
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 Safety Monitor of the SAE by email, ensuring that the subject 
information is deidentified (only subject initials and subject number) to: ProPharma, 
Email: clinicalsafety@propharmagroup.com. 
3. Print a copy of the email confirmation from ProPharma and place in the study file. 
4. Within 24-hours complete, as fully as possible, an AE eCRF and an SAE form; e-mail the 
forms and any other relevant information (e.g., concomitant medication eCRF, medical 
history eCRF, laboratory test results) to ProPharma. 
5. 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 


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Therapeutics, Inc.  Safety and Medical Monitor agree that the SAE is satisfactorily 
resolved. 
6. Inform the Aclaris Therapeutics, Inc. Safety Monitor of SAE updates, via telephone, 
followed by an SAE form update sent by e-mail. 
7. Comply with the appropriate regulatory requirements and Aclaris Therapeutics, Inc. 
instructions regarding reporting of the SAE to the responsible Institutional Review Board 
(IRB) or Ethics Committee (EC). 
13.4. 
Pregnancy 
13.4.1. 
Definition of Woman of Child Bearing Potential (WOCBP) 
WOCBP includes any female who has experienced menarche and who has not undergone 
successful surgical sterilization (e.g., hysterectomy, bilateral tubal ligation, or bilateral 
oophorectomy) or is not postmenopausal. Postmenopausal is defined as ≥12 months with no 
menses without an alternative medical cause.  WOCBP must have a negative serum pregnancy 
test at screening and a negative UPT at Baseline prior to randomization. 
13.4.2. 
Highly Effective Methods of Birth Control 
The Investigator or sub-investigator will discuss the potential risk factors associated with 
pregnancy and the importance of maintaining a highly effective method of contraception 
throughout the study with all WOCBP (for example, those which result in a low failure rate - i.e., 
less than 1% per year- when used consistently and correctly).  All WOCBP must use a highly 
effective method of birth control during the study and for 30 days after the final dose of study 
medication in a manner such that risk of failure is minimized.   
 
Highly effective methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 
o implantable 
• intrauterine device (IUD) 
• obstruction of fallopian tubes via medical device (Essure™) 
• intrauterine hormone-releasing system (IUS) 
• vasectomized partner1 
• sexual abstinence2 
1Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner 
of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the 
surgical success.  
2 Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study treatments. The reliability of sexual 


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abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual 
lifestyle of the subject. 
 
WOCBP must be on a highly effective method of birth control for the following timeframes prior 
to study entry:  
• Implants (on a stable dose for ≥30 days) 
• Injectables (on a stable dose for ≥30 days) 
• Patches (on a stable dose for ≥30 days) 
• Combined oral contraceptives (on a stable dose for ≥30 days) 
• Intrauterine devices (inserted for ≥30 days). 
Prior to trial enrollment, WOCBP must be advised of the importance of avoiding pregnancy 
during trial participation and of the potential risk factors associated with pregnancy while in the 
study.  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 or partner of a 
male 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, the investigator must report every pregnancy using a pregnancy 
surveillance form and follow the reporting procedures described for SAE reporting. 
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. 
 
 
 
 
 


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14. 
STATISTICS 
14.1. 
Statistical Methods 
Safety and efficacy results will be summarized and presented by visit, with no inferential 
statistics presented.  Parameters related to safety and tolerability will be treated as primary 
analysis variables.  Efficacy parameters will be treated as secondary endpoints. 
 
All data will be summarized by visit, with presentations based on the nature of the parameter.  
For binary data such as presence or absence of treatment-emergent adverse events, the incidence 
will be presented along with the overall number of subjects and percentages.  External clinical 
laboratory and similar externally sourced data will be summarized as binary outcomes based on 
the determination of values beyond applicable normal ranges, and in some cases the assessment 
of clinical significance of deviations from normal ranges.  For ordinal categorical data including 
efficacy data from PGA, EASI, SPA and SAD scores, and continuous data such as affected body 
surface area, summary statistics will be presented including N, mean, median, standard 
deviation, and standard error, by visit.  Where applicable, the mean changes from baseline for 
ordinal categorical and continuous parameters will be presented by visit, along with N, median, 
standard deviation and standard error. 
14.2. 
Analysis of Efficacy Outcome Measures 
Subject responder analyses will be conducted, by visit, based on the following criteria: 
 
• The proportion of subjects whose active-treated lesions are judged to be clear or near 
clear on the PGA (PGA = ≤ 1) with a 2 grade or greater improvement from baseline; 
• The proportion of subjects whose active-treated lesions are judged to be clear on the PGA 
(PGA = 0);  
• The proportion of subjects who had an improvement from baseline of at least 75% in 
EASI score (EASI – 75). 
 
Other subject responder criteria will be established as appropriate from data observation and the 
results will be presented as above.   


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15. 
TRAINING, DATA HANDLING AND RECORDKEEPING 
15.1. 
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 eCRFs.  Those unable to attend the 
initiation visit must receive on-site training from an appropriately trained individual prior to 
participating in any of the procedures and evaluations in this study.  
Clinical Research Associates (CRAs) and other applicable personnel will be trained prior to 
study initiation to familiarize CRAs with the disease, the Standard Operating Procedures (SOPs), 
the protocol and other study specific items.  Team organization, communication and operational 
issues will also be discussed. 
Aclaris Therapeutics, Inc. will provide an investigational center file to each center. 
15.2. 
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 eCRFs.  All data on these eCRFs should 
be recorded completely and promptly.  A copy of the completed eCRFs for each subject will be 
retained by the investigational center. 
Records of the subject’s participation in this study will be held confidential except as disclosure 
is required by law. The study doctor, the sponsor, persons working on behalf of the sponsor, and 
under certain circumstances, the United States Food and Drug Administration and the 
Institutional Review Board will be able to inspect and copy confidential study-related records 
that identify subjects by name. Therefore, absolute subject confidentiality cannot be guaranteed. 
If the results of this study are published or presented at meetings, the subject’s identity will not 
be revealed. 
15.3. 
Protocol Violations and Deviations 
A protocol deviation is defined as an accidental or unintentional change to, or non-compliance 
with the research protocol that does not increase risk or decrease benefit or; does not have a 
significant effect on the subject’s right, safety, or welfare; and/or on the integrity of the data.  
Deviations may result from the action of the subject, researcher or research staff.  A protocol 
deviation does not involve inclusion/exclusion criteria. 
A protocol violation is defined as an accidental or unintentional change to, or non-compliance 
with the IRB approved protocol without prior sponsor approval.  Protocol violations generally 
increase risk or decrease benefit, affects the subject’s rights, safety, or welfare, or the integrity of 
the data.   
15.4. 
Study Monitoring 
 


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Before an investigational site can enter a patient into the study, a representative of Aclaris 
Therapeutics, Inc. will visit the investigational study site to: 
• Determine the adequacy of the facilities 
• Discuss with the investigator(s) and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of Aclaris Therapeutics, Inc. or its 
representatives.  This will be documented in a Clinical Study Agreement between Aclaris 
Therapeutics, Inc. and the investigator. 
During the study, a monitor from Aclaris Therapeutics, Inc. or representative will have regular 
contacts with the investigational site, for the following: 
• Provide information and support to the investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the case report forms, and that investigational product 
accountability checks are being performed 
• Perform source data verification.  This includes a comparison of the data in the case 
report forms with the patient’s medical records at the hospital or practice, and other 
records relevant to the study.  This will require direct access to all original records for 
each patient (e.g. clinic charts). 
• Record and report any protocol deviations not previously sent to Aclaris Therapeutics, 
Inc. 
• Confirm AEs and SAEs have been properly documented on CRFs and confirm any SAEs 
have been forwarded to Aclaris Therapeutics, Inc. and those SAEs that met criteria for 
reporting have been forwarded to the IRB. 
The monitor will be available between visits if the investigator(s) or other staff needs 
information or advice. 
15.5. 
Source Documentation 
Investigators must keep accurate separate records (other than the eCRFs) 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. 
15.6. 
Inspection of Records 
 
Aclaris will be allowed to conduct site visits to the investigation facilities for the purpose of 
monitoring any aspect of the study. The Investigator agrees to allow the monitor to inspect the 
drug storage area, study medication stocks, drug accountability records, subject charts and study 
source documents, and other records relative to study conduct. 
 


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15.7. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 2 
years after the last marketing application approval, or if not approved 2 years following the 
discontinuance of the test article for investigation. If it becomes necessary for Aclaris or the 
Regulatory Authority to review any documentation relating to the study, the Investigator must 
permit access to such records. 
 


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16. 
QUALITY CONTROL AND 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, Declaration of 
Helsinki, and in respect of the Aclaris Therapeutics, Inc. and/or sub-contractor SOPs for study 
conduct and monitoring. 
Audits may be carried out by Aclaris Therapeutics, Inc. or 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., eCRFs, 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. 


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17. 
ETHICS 
17.1. 
Ethics Review 
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. 
17.2. 
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. 
17.3. 
Written Informed Consent 
The Principal Investigator(s) at each center will ensure that the subject is given full and adequate 
oral and written information about the nature, purpose, possible risk and benefit of the study.  
Subjects must also be notified that they are free to discontinue from the study at any time.  The 
subject should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The subject’s signed and dated informed consent must be obtained before conducting any study 
procedures.  The Principal Investigator(s) must maintain the original, signed Informed Consent 
Form.  A copy of the signed Informed Consent Form must be given to the subject. 
17.4. 
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.’s representative or designee 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.  A protocol deviation is a non-
adherence to protocol-specific study procedures or schedules that does not increase the risk to a 
study subject and does not affect the scientific integrity of the study.   
 
A protocol violation is defined as any divergence from the protocol-specific study procedures or 
schedules that may result in an increased risk to a study subject or that affect the scientific 
integrity of the study.  All protocol violations must be reviewed by the Medical Monitor and 
reported to the IRB by the Investigator, as directed by the IRB-specific procedures. 
 


Protocol:  ATI-502-AD-201 
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Amendment 1  
 
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17.5. 
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. 
17.6. 
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:  ATI-502-AD-201 
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18. 
REFERENCES 
1. Alves de Medeiros A.K., Speeckaert R., Desmet E., et al. 2016.  JAK3 as an emerging 
target for topical treatment of inflammatory skin diseases.  PLoSONE 11 (10): e0164080 
2. Bissonnette, R., K.A.Papp, Y.Poulin et. al. 2016.  Topical Tofacitinib for atopic 
dermatitis:  a phase II a randomized trial.  Br. J. Dermatology.  175:  901-911 
3. Eyerich K. and N. Novak. 2013.  Immunology of atopic eczema:  overcoming the 
Th1/Th2 paradigm.  Allergy 68:  974-982. 
4. Hanifin JM, et.al. The eczema area and severity index (EASI):  assessment of reliability 
in atopic dermatitis.  EASI Evaluator Group. Exp. Dermatology.  2001 FEB; 10(1):  11-8. 
5. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis.  Acta Derm Venereol 
Suppl 1980; 92:  44-7. 
6. Levy, L.L. J. Urban and B.A. King. 2015.  Treatment of recalcitrant atopic dermatitis 
with oral Janus kinase inhibitor tofacitinib citrate.  J Am Acad Dermatology 73 (3):  395-
399.   
7. Weston, W. L. and Howe, W. 2017. Atopic dermatitis (eczema):  Pathogenesis, clinical 
manifestations, and diagnosis.  UpToDate.com.   


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19. 
APPENDICES 


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APPENDIX 1. SUBJECT INSTRUCTIONS 
Preparation and General Instructions:  
 
1. Gather a clean washcloth and towel, the study medication bottle, and disposable dropper. 
2. Skin should be clean and dry before applying study medication.   
3. Refrain from bathing, swimming and/or participating in strenuous exercise that would cause 
profuse sweating for 6 hours after application of study medication.       
4. Refrain from applying moisturizers, emollients and sunscreen to AD treatment areas for the 
duration of protocol therapy.  Moisturizers, emollients and sunscreens may be applied to non-AD 
treatment areas.     
5. Wash your hands with soap and water before and after using this study medication.  
6. Apply a thin layer of study medication to the identified AD target skin area as instructed by the 
study doctor or the study staff.  Keep applying study medication to the area throughout the study, 
even if the skin begins to clear.  If new areas of AD appear, study medication may be applied to 
these areas.  
7. Avoid study medication contact with the eye.  
8. You will apply study medication twice-a-day, approximately 12 hours apart.   
9. Remember to bring your study medication bottles both used and unused to each study visit. 
 
Study Medication Application: 
1. Draw up exactly 1 mL of study medication into the dropper. The medication level should be at 
the 1mL line.  
2. During study medication application, avoid any study medication running into your eyes.   
3. Squeeze a few drops of study medication onto the center of the identified target AD area and 
gently rub the study medication into your skin. Keep applying a few drops and rubbing into your 
skin until the entire area is covered with a thin film of study medication.    
4. Draw up additional medication - 1 mL at a time- to cover the entire AD area.   
5. Replace the screw top cap and make sure it is closed tightly.  Dispose of the used dropper(s). 
6. It is important to continue to apply study medication to the target AD areas throughout the study, 
even if the skin begins to clear.     
7. Wash your hands after using this product to prevent any residue being left on your hands. 
8. If you missed a dose or doses, tell the study staff at your next visit.     
Missed Doses: If you miss a dose of this study medicine, apply it as soon as possible. However, if it is 
almost time for your next dose, skip the missed dose, and go back to your regular dosing schedule. 
 
Storage: Store the medicine in the original glass bottle in the carton provided at room temperature, away 
from heat, moisture, and direct light. Keep from freezing.  Keep out of the reach of children. 
 


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APPENDIX 2. HANIFIN AND RAJKA DIAGNOSTIC CRITERIA FOR 
ATOPIC DERMATITIS 
 
Hanifin and Rajka Diagnostic Criteria for Atopic Dermatitis (AD) 
Major criteria: Must have three or more of: 
1. Pruritus 
2. Typical morphology and distribution  
• Flexural lichenification or linearity in adults 
• Facial and extensor involvement in infants and children 
3. Chronic or chronically-relapsing dermatitis 
4. Personal or family history of atopy (asthma, allergic rhinitis, 
atopic dermatitis) 
Minor criteria: Should have three or more of: 
1. Xerosis 
2. Ichthyosis, palmar hyperlinearity, or keratosis pilaris 
3. Immediate (type 1) skin-test reactivity 
4. Raised serum IgE 
5. Early age of onset 
6. Tendency toward cutaneous infections (especially S aureus 
and herpes simplex) or impaired cell-mediated immunity 
7. Tendency toward non-specific hand or foot dermatitis 
8. Nipple eczema 
9. Cheilitis 
10. Recurrent conjunctivitis 
11. Dennie-Morgan infraorbital fold 
12. Keratoconus 
13. Anterior subcapsular cataracts 
14. Orbital darkening 
15. Facial pallor or facial erythema 
16. Pityriasis alba 
17. Anterior neck folds 
18. Itch when sweating 
19. Intolerance to wool and lipid solvents 
20. Perifollicular accentuation 
21. Food intolerance 
22. Course influenced by environmental or emotional factors 
23. White dermographism or delayed blanch 
(Hanifin, 1980) 
 
 

SAP_001.pdf: 


Aclaris Therapeutics Inc. 
14 May 2019 
Protocol: ATI-502-AD-201 
Statistical Analysis Plan 
 
Page 2 of 11 
 
TABLE OF CONTENTS 
1. 
STUDY OBJECTIVES .................................................................................. 3 
1.1 Primary Objective .............................................................................................. 3 
1.2 Secondary Objectives ........................................................................................ 3 
2. 
STUDY DESIGN ........................................................................................... 3 
3. 
SCHEDULE OF ASSESSMENTS ................................................................ 4 
4. 
STATISTICAL METHODS ........................................................................... 7 
4.1 Study Population, Disposition, Baseline Characteristics, Medical 
History Concomitant Medications, Exposure and Protocol 
Violations .................................................................................................... 7 
4.1.1 
Analysis Populations ...................................................................... 7 
4.1.2 
Subject Disposition......................................................................... 7 
4.1.3 
Demographic and Baseline Characteristics .................................... 7 
4.1.4 
Diagnosis and Prior Therapies and Treatments for 
Atopic Dermatitis ........................................................................... 7 
4.1.5 
History of Allergies......................................................................... 7 
4.1.6 
Prior and Concomitant Medications, Therapies and 
Procedures ...................................................................................... 8 
4.1.7 
Exposure to Study Medication and Study Medication 
Administration ................................................................................ 8 
4.1.8 
Major Protocol Violations .............................................................. 8 
4.2 Efficacy Endpoints ............................................................................................ 8 
4.2.1 
Eczema Area and Severity Index (EASI) ....................................... 8 
4.2.1 
Subject Pruritus Assessment (SPA) ................................................ 8 
4.2.2 
Signs of Atopic Dermatitis (SAD) .................................................. 9 
4.2.3 
Physician Global Assessment (PGA) ............................................. 9 
4.2.4 
Body Surface Area of AD ............................................................... 9 
4.3 Safety Analyses.................................................................................................. 9 
4.3.1 
Adverse Events ............................................................................... 9 
4.3.2 
Physical Examinations.................................................................. 10 
4.3.3 
Vital Signs .................................................................................... 10 
4.3.4 
ECG assessments .......................................................................... 10 
4.3.5 
Laboratory Evaluations ................................................................. 10 
4.4 Sample Size ..................................................................................................... 10 
4.5 Changes in/ Clarifications to the Conduct of the Study or 
Planned Analysis ....................................................................................... 10 
5. 
STATISTICAL SOFTWARE ....................................................................... 11 
 


Aclaris Therapeutics Inc. 
14 May 2019 
Protocol: ATI-502-AD-201 
Statistical Analysis Plan 
 
Page 3 of 11 
 
INTRODUCTION 
 
The purpose of this statistical analysis plan (SAP) is to provide a description of the 
statistical analyses performed for the Phase 2a protocol, ATI-502-AD-201, V1.0 
(23Apr2018). 
1. 
STUDY OBJECTIVES 
1.1 Primary Objective 
The primary objective for this study is to assess the safety and tolerability of ATI-502 
Topical Solution, 0.46% in subjects with moderate to severe atopic dermatitis. 
1.2 Secondary Objectives 
The secondary outcome measures for this study are to assess the following: 
• 
Change from baseline in Physician Global Assessment (PGA) score following 4 
weeks of treatment with ATI-502 Topical Solution, 0.46% 
• 
Change from baseline in body surface area affected by atopic dermatitis following 
4 weeks of treatment with ATI-502 Topical Solution, 0.46%. 
• 
Change from baseline in Eczema Area and Severity Index (EASI) score following 
4 weeks of treatment with ATI-502 Topical Solution, 0.46%. 
• 
Change from baseline in the subjects Signs of Atopic Dermatitis (SAD) 
assessment following 4 weeks of treatment with ATI-502 Topical Solution, 0.46%. 
• 
Change from baseline in Subjects Pruritus Assessment (SPA) score following 4 
weeks of treatment with ATI-502 Topical Solution, 0.46%... 
2. 
STUDY DESIGN 
  
This is an open label, multicenter, phase 2a study designed to evaluate the safety and 
tolerability of ATI-502 Topical Solution, 0.46% in male and female subjects with a 
diagnosis of AD as defined by the Hanifin and Rajka criteria. Based on the 5-point 
Physician’s Global Assessment (PGA) scale, subjects must have a score of 3 (moderate) 
or 4 (severe). Subjects will be required to apply ATI-502 study medication to their 
identified AD treatment areas twice a day (BID) for a total of 4 weeks. Subjects will be 
allowed to treat new disease areas with ATI-502 Topical Solution, 0.46% if they appear 
after Visit 2. All subjects will be required to complete a safety follow up visit 4 weeks 
post last study medication application. 
 


Aclaris Therapeutics Inc. 
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Protocol: ATI-502-AD-201 
Statistical Analysis Plan 
 
Page 4 of 11 
 
A total of 30 evaluable subjects who are ≥ 18 years of age with a clinical diagnosis of 
moderate or severe AD will be enrolled to the study.   
 
Safety and tolerability will be evaluated by assessment of adverse events, physical 
examinations, vital signs, ECGs and clinical laboratory tests. 
 
3. 
SCHEDULE OF ASSESSMENTS 
The study schedule of assessments can be found in Table 1. 


Aclaris Therapeutics Inc. 
14 May 2019 
Protocol: ATI-502-AD-201 
Statistical Analysis Plan 
 
Page 5 of 11 
 
Table 1  Schedule of Assessments 
Screening 
Baseline 
Treatment 
Post Treatment 
Safety Follow up 
Visit13 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Week 
0 
1 
2 
4 
8 
Treatment Day 
-14 to 0 
1 
8 
15 
29 
56 
Treatment Window(days) 
N/A 
N/A 
± 3 
± 3 
± 3 
+7 
Informed consent1 
▲ 
Inclusion/exclusion criteria 
▲ 
▲ 
Physical exam2 
▲ 
▲ 
Demographics & Medical History 
▲ 
Vital Signs3 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Fitzpatrick Skin Type 
▲ 
Atopic Dermatitis History 4 
▲ 
Clinical Chemistry and CBC5 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
QuantiFERON Gold6 
▲ 
Virology [HepB (HBsAg), HCV (antibody), HIV 
(antibody)] 
▲7 
Serum Pregnancy 
▲ 
Urine Pregnancy 
▲ 
▲ 
ECG 
▲ 
▲ 
▲ 
▲ 
▲ 
Physician’s Global Assessment (PGA) 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Body Surface Areas Assessment 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Identification of AD Treatment Area 
▲ 
▲ 
Eczema Area and Severity Index (EASI) 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Subjects Pruritus Assessment (SPA) 
▲ 
▲ 
▲ 
▲ 
▲ 
Signs of Atopic Dermatitis (SAD) 
▲ 
▲ 
▲ 
▲ 
▲ 
Standardized Photography8 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Dispensing of study medication9 
▲ 
▲ 
▲ 
Treatment with ATI-502 
▲10 
▲ 
▲ 
▲ 
Subject Instructions11 
▲ 
▲ 
▲ 
▲ 
▲ 
Concomitant medications/therapies 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 
Adverse Events12 
▲ 
▲ 
▲ 
▲ 
▲ 
▲ 


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Statistical Analysis Plan 
 
Page 6 of 11 
 
1  A written, signed ICF must be obtained from each subject prior to performing any study related procedure. 
2 A physical exam includes: general appearance, examination of head, eyes, ears, nose and throat, extremities, respiratory, cardiovascular, abdominal, neurological, musculoskeletal, 
lymphatic and skin assessment. 
3 Vital signs include: oral or ear temperature, blood pressure, heart rate, respiration rate (height and weight at baseline only). 
4  Prior therapies or treatments a subject received to treat AD must be documented for each subject. 
5 Serum chemistry panel to include: albumin, alkaline phosphatase, ALT, AST, BUN, bicarbonate, calcium, chloride, creatinine, glucose, lactate dehydrogenase (LDH), phosphorus, 
potassium, sodium, total bilirubin, total protein, uric acid, total cholesterol, LDL, HDL triglycerides, and complete blood count including differential. 
6 All subjects must have a blood sample drawn to test for the tuberculosis virus (QuantiFERON Gold). The blood sample will be sent to a central laboratory for analysis and results must be 
received prior to enrolling the subject. 
7 All subjects will be required to have virology testing for HepB (HBsAG), HCV(antibody), and HIV (antibody). If a subject demonstrates to have serological evidence HepB (HBsAG), 
HCV (antibody) or HIV (antibody), the subject will not be allowed to enroll to the study. 
8 Canfield staff will review all photographs within 2 days of the photographs being submitted. If a re-take is required, Canfield will notify the site and the re-take photographs will need to be 
performed within 7 days of the visit. Prior to enrollment to the study, each subject’s Visit 1 photos will be reviewed by a panel of board certified dermatologists to ensure that the subject’s 
target areas for treatment meet the study entry criteria. 
9 At visit 2, following confirmation that the subject is approved for enrollment to the study, the site will weigh and dispense supplies of ATI-502 study medication and disposable droppers to 
the subject for at home application of the study medication. 
10 All subjects will have their first application of study medication applied in the clinic during Visit 2. Subjects will continue to apply ATI-502 Topical Solution, 0.46% to all target areas 
twice a day for 4 weeks (Day 28) unless the subject meets the criteria for treatment interruption. If new areas of AD develop, subjects will be allowed to treat these areas with the ATI-502 
study medication. 
11 Sites will be required to review with each subject the proper application of the study medication and remind that they must refrain from exercise that may cause excessive sweating, 
bathing or swimming for a period of 6 hours after the application of study medication. Subjects are also to be reminded that they may not apply moisturizers, emollients, or sunscreen to 
target AD areas during protocol treatment. 
12 All non-serious AEs will be collected from the time of first study medication application until the final study visit. Serious AEs will be collected from the time of consent through the final 
study visit. 
13A final safety follow up visit will be conducted at week 8 (Visit 6). For those subjects that discontinue the study early, they must return to the clinic 4 weeks following the last study 
medication application for a final safety visit. 
  


7Aclaris Therapeutics Inc. 
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Protocol: ATI-502-AD-201 
Statistical Analysis Plan 
 
 
 CONFIDENTIAL 
Page 7 of 11 
4. 
STATISTICAL METHODS  
Summaries will be presented for all subjects combined.  
All Data listings will be sorted by subject ID, and where applicable date/study day. 
4.1 Study Population, Disposition, Baseline Characteristics, Medical History 
Concomitant Medications, Exposure and Protocol Violations 
4.1.1 Analysis Populations 
Safety Population: Includes all subjects with at least one application of study medication. 
The Safety Population will be used for all safety analyses. 
 
Efficacy Population: Includes all subjects with at least one application of study 
medication. The Efficacy Population will be used for all efficacy analyses. 
 
Per-Protocol (PP) Population:  Includes all subjects who completed Visit 6 (Week 8).  The 
PP Population will be used for sensitivity assessments of key efficacy analyses. 
 
4.1.2 Subject Disposition 
The number of subjects in the Safety population will be presented with the study 
completion status and the reasons for discontinuation.  
4.1.3 Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be presented in the data listings.  
Descriptive summary statistics (n, mean, standard deviation, median, minimum, and 
maximum) and/or frequency distributions, as appropriate, will be generated for the Safety 
population.   
4.1.4 Diagnosis and Prior Therapies and Treatments for Atopic 
Dermatitis 
Prior therapies and treatment for atopic dermatitis will be summarized by frequency 
distributions. The time since diagnosis of atopic dermatitis will be summarized using 
descriptive statistics (n, mean, standard deviation, median, minimum, and maximum).  
Summaries will be generated for the Safety Population. 
4.1.5 History of Allergies 
Allergy history will be listed. 


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4.1.6 Prior 
and 
Concomitant 
Medications, 
Therapies 
and 
Procedures 
Medications will be coded using the WHO Drug Reference (B3 Format Sept 2018).  Prior 
and concomitant medications will be listed only.  The period(s) in which the medications 
were administered will be flagged. 
4.1.7 Exposure to Study Medication and Study Medication 
Administration 
Exposure will be summarized and listed for the Safety population. The duration of 
treatment, total weight, total volume, and average volume per application will be 
summarized using descriptive statistics (n, mean, SD, median, minimum and maximum).  
4.1.8 Major Protocol Violations 
Protocol violations will be identified to measure adherence to key aspects the protocol.  
Prior to analysis, the sponsor will assess the data and identify all protocol violations.  
Specific data fields that will be examined to identify protocol violations include entrance 
inclusion/exclusion criteria and prohibited prior and concomitant medications as well as 
all violations identified by the investigator. All protocol violations will be listed. 
4.2 Efficacy Endpoints 
The baseline for all efficacy measures will be the last non-missing value collected on or 
before the date of the first application of study medication.  Analyses of post-baseline 
data will be performed on observed (non-missing) data based on nominal visits as 
collected on the CRF. 
4.2.1 Eczema Area and Severity Index (EASI) 
Descriptive statistics (N, mean, SD, median, minimum and maximum) for the absolute 
EASI, change, and percent change from baseline will be tabulated by visit.  Change will 
be computed as the timepoint score – baseline score. Percent change as 100*change ÷ 
baseline. A categorical summary of the number and percentage of subjects achieving a 
75% or greater decrease in EASI will be provided by visit as well as those achieving the 
response at any post-baseline visit.  Likewise, a categorical summary of the number and 
percent of subjects achieving a 50% or greater decrease in EASI will be provided.  This 
categorical summary of the EASI will be conducted on both the Efficacy Population and 
the PP population, separately. 
4.2.1 Subject Pruritus Assessment (SPA) 
Descriptive statistics (N, mean, SD, median, minimum and maximum) for the absolute 
SPA, change, and percent change from baseline will be tabulated by visit.  Change will be 
computed as the timepoint score – baseline score. Percent change as 100*change ÷ 


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baseline. 
4.2.2 Signs of Atopic Dermatitis (SAD) 
For each symptom (erythema, induration, lichenification, excoriation, exudation), the 
number and percentage of subjects with a score of 0 (none), ≤ 1 (None or Mild) and 
improved by at least 1 level from baseline will be tabulated by visit.  This categorical 
summary for the SAD will be conducted on both the Efficacy Population and the PP 
population, separately 
4.2.3 Physician Global Assessment (PGA) 
The number and percentage pf patents achieving a PGA score ≤ 1 (Clear or Almost Clear) 
as well as those with PGA score=0 (Clear) will be tabulated by visit.  Scores of 1 or less 
represent at least a 2-grade improvement from the protocol inclusion criteria of PGA 3 or 
4.  This categorical summary of the PGA will be conducted on both the Efficacy 
Population and the PP population, separately. 
4.2.4 Body Surface Area of AD 
The body surface area of AD will be summarized descriptively (N, mean, SD, median, 
minimum and maximum) for the absolute BSA, change, and percent change from 
baseline by visit.  Change will be computed as the timepoint score – baseline score. 
Percent change as 100*change ÷ baseline. 
4.3 Safety Analyses 
The comprehensive safety analysis is based on all subjects in the Safety population.  
The following sections detail the summaries performed on the safety data. Additional data 
handling rules including those for imputation of partially missing dates will be provided 
in a separate SAP document pertaining to data handling and programming specifications. 
The baseline scores for vital signs, laboratory assessments and ECGs will be the last non-
missing value collected on or before the date of the first application of study medication. 
This baseline will also be used for calculating change from baseline.     
4.3.1 Adverse Events 
Adverse events will be coded using the MedDRA dictionary V21.1 and will be 
categorized by system organ class (SOC) and preferred term (PT).  Only treatment 
emergent adverse events will be included in summary tabulation. All adverse events, 
including those that are not considered treatment emergent, will be included in the data 
listings.   


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To differentiate the study period in which an Adverse Event occurred, three categories 
will be defined based upon onset date. Adverse Events that had onset dates prior to the 
first application of study medication will be considered "prior”. Adverse events with 
onset dates on or after the first application of study medication and within 30 days 
following the last application of study medication will be considered "on therapy" or 
equivalently “treatment emergent”.  Events with onset dates more than 30 days after the 
last application of study medication will be considered as "post-therapy".   
   
Frequency tabulations will be presented by MedDRA SOC and preferred term, for all 
adverse events; study treatment-related, adverse events resulting in discontinuation of 
study treatment, serious adverse events and adverse events by maximum severity. Adverse 
events resulting in discontinuation will be those with ‘action taken’ recorded as ‘drug 
withdrawn’. 
4.3.2 Physical Examinations 
Physical examination findings will be listed for each subject. 
4.3.3 Vital Signs 
Systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate and 
temperature will be summarized using descriptive statistics for each visit. Both actual 
values and changes from baseline will be summarized. 
4.3.4 ECG assessments 
The core laboratory’s interpretation of the ECGs will be summarized as “shift” from 
baseline to “worst” overall interpretation recorded after baseline where the order of 
severity of the interpretations from best to worst will be “Normal”, “Abnormal, NCS” and 
“Abnormal, CS”.   
4.3.5 Laboratory Evaluations 
Chemistry and Hematology parameters will be summarized using descriptive statistics for 
each visit. Both actual values and changes from baseline will be summarized. 
The number and percentage of subjects meeting criteria for hepatobiliary abnormalities 
and for potential renal impairment will also be provided. 
4.4 Sample Size 
Sample size for this study was not based upon formal statistical criteria. A total of 30 
subjects is planned. 
 
4.5 Changes in/ Clarifications to the Conduct of the Study or Planned 
Analysis 
  In addition to the EASI-75 planned in the protocol, an EASI-50 has been added.  


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Sensitivity assessments of key efficacy analyses was included that was not specified in the 
protocol.   
5. 
STATISTICAL SOFTWARE 
All data summaries and listings will be performed using SAS Version 9.2 or higher, 
under Windows operating system.