Clinical trial NCT03551821
Conditions: Alopecia Areata Alopecia Totalis Alopecia Universalis
Sponsor: Aclaris Therapeutics, Inc.
Start date: 2018-04-11; Completion date: 2018-11-06
Enrollment: 1 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The main objective of this study is to assess the safety, tolerability and efficacy of ATI-50002 Topical Solution in subjects with unilateral or bilateral loss of eyebrow hair due to alopecia areata (AA), alopecia universalis (AU) or alopecia totalis (AT).

Detailed description:
This is an open-label study which will be conducted at 1 to 2 sites.

Subjects will be required to have a clinical diagnosis of AA, AU or AT with unilateral or bilateral loss of eyebrow hair.

Subjects will apply study medication to the entire affected eyebrow(s), twice-daily for 24 weeks.

Safety and tolerability will be evaluated throughout the study.

The duration of the study participation is anticipated to be a maximum of 233 days.

Arms: arm 1: ATI-50002 Topical Solution
Interventions: intervention 1: ATI-50002
Intervention descriptions: intervention 1: Topical Solution

Protocol documents:
Prot_SAP_000.pdf: 
Aclaris Therapeutics, Inc.  
Protocol Number: ATI-50002-AAB-201 
CONFIDENTIAL 
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CLINICAL STUDY PROTOCOL 
 
Protocol Number: ATI-50002-AAB-201 
 
An Open-Label Pilot Study of the Safety, Tolerability and Efficacy of ATI-50002 Topical 
Solution Administered Twice-Daily in Adult Subjects with Eyebrow Loss Due to Alopecia 
Areata, Alopecia Universalis or Alopecia Totalis 
 
Sponsor 
Aclaris Therapeutics, Inc. 
640 Lee Rd. 
Suite 200 
Wayne, PA 19087 
Telephone: (484) 324-7933 
Facsimile: (484) 320-2344 
 
Study Contact 
Susan Moran, RN, MSN 
Sr. Director, Clinical Development 
Aclaris Therapeutics, Inc. 
640 Lee Rd. 
Suite 200 
Wayne, PA 19087 
Telephone: (484) 329-2129 
Mobile: (717) 781-7444 
E-mail: smoran@aclaristx.com 
 
Medical Monitor 
Terrence Chew, MD RAC 
Aclaris Therapeutics, Inc. 
640 Lee Rd. 
Suite 200 
Wayne, PA 19087 
Telephone: (858) 720-0647 
E-mail: tgchew@icloud.com 
 
Safety Monitor: 
ProPharma 
E-mail: clinicalsafety@propharmagroup.com 
Serious Adverse Event Facsimile: (866)-681-1063 
 
This document is a privileged and confidential communication of Aclaris Therapeutics, Inc. Acceptance of this document 
constitutes an agreement by the recipient that no unpublished information contained herein will be used, published or disclosed 
without prior written approval from Aclaris Therapeutics, Inc. 




Protocol: ATI-50002-AAB-201 
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INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: ATI-50002-AAB-201 
 
Protocol Title: An Open-label Pilot Study of the Safety, Tolerability and Efficacy of ATI-50002 Topical 
Solution Administered Twice-Daily in Adult Subjects with Eyebrow Loss due to Alopecia Areata, 
Alopecia Universalis or Alopecia Totalis 
 
Protocol Version: 1.0 06FEB2018 
 
I have reviewed the above-titled protocol and agree that it contains all the information necessary to 
conduct the study as required. I will conduct the trial in accordance with the principles of ICH Good 
Clinical Practice and the Declaration of Helsinki. 
 
I will maintain as confidential all written and verbal information provided to me by the Sponsor, 
including but not limited to, the protocol, case report forms, investigator’s brochure, material supplied at 
investigator meetings, minutes of teleconferences, etc. Such material will only be provided as necessary 
to site personnel involved in the conduct of the trial, involved Institutional Review Board (IRB), Ethics 
Committees, 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, 
but no later than five days following the initial notification. 
 
 
_________________________________________________________ 
Investigator Name (Print) 
 
 
_________________________________________________________         _______________________ 
Investigator Signature                                                                                        Date 
 
 


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Table of Contents 
1. 
SYNOPSIS ..................................................................................................................................................... 7 
2. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................................................ 13 
3. 
INTRODUCTION ...................................................................................................................................... 15 
3.1. 
Summary ................................................................................................................................................... 15 
3.2. 
Study Rationale ........................................................................................................................................ 18 
4. 
STUDY OBJECTIVES ............................................................................................................................. 18 
5. 
SELECTION AND DISPOSITION OF STUDY POPULATION .................................................. 18 
5.1. 
Number of Subjects ................................................................................................................................. 18 
5.2. 
Study Population Characteristics ........................................................................................................ 19 
5.3. 
Inclusion Criteria .................................................................................................................................... 19 
5.4. 
Exclusion Criteria ................................................................................................................................... 20 
5.5. 
Concomitant Therapies .......................................................................................................................... 21 
5.5.1. 
Permitted Concomitant Therapies ................................................................................................... 22 
5.5.2. 
Prohibited therapies ............................................................................................................................. 22 
5.6. 
Subject Discontinuation from the Study ............................................................................................ 22 
5.7. 
Subject Identifier (SI) ............................................................................................................................. 23 
5.8. 
Replacement Subjects ............................................................................................................................. 23 
6. 
INVESTIGATIONAL PLAN .................................................................................................................. 23 
6.1. 
Study Design ............................................................................................................................................. 23 
6.2. 
Study Flow Chart .................................................................................................................................... 24 
6.3. 
Study Visits Description and Procedures .......................................................................................... 25 
6.3.1. 
Visit 1/ Screening (Week -4 to 0) ....................................................................................................... 25 
6.3.2. 
Visit 2/ Baseline (Day 1) ...................................................................................................................... 26 
6.3.3. 
Visits 3-9 (Weeks 1, 2, 4, 8, 12, 16 and 20) ...................................................................................... 27 
6.3.4. 
Visit 10 (Week 24) ................................................................................................................................. 28 
6.3.5. 
Visit 11 (Week 28) ................................................................................................................................. 28 
6.4. 
Subject Instructions ................................................................................................................................ 29 
6.5. 
STUDY DURATION .............................................................................................................................. 29 
6.6. 
STUDY MEDICATIONS ...................................................................................................................... 30 
6.6.1. 
Study medication identity ................................................................................................................... 30 
6.6.2. 
Study medication packaging and labeling ...................................................................................... 31 
6.6.3. 
Method of treatment assignment ...................................................................................................... 31 


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6.6.4. 
Subject Eligibility to Receive Study Medication ........................................................................... 31 
6.6.5. 
Dispensing and collecting study medication ................................................................................... 31 
6.6.6. 
Study medication application ............................................................................................................ 32 
6.6.7. 
Dose compliance record ...................................................................................................................... 32 
6.6.8. 
Dose modification ................................................................................................................................. 32 
6.7. 
Study Medication Management ........................................................................................................... 33 
6.7.1. 
Accountability ....................................................................................................................................... 33 
6.7.2. 
Return and disposition of study supplies ........................................................................................ 33 
6.8. 
Other Study Supplies .............................................................................................................................. 33 
6.9. 
Blinding ...................................................................................................................................................... 33 
6.9.1. 
Verification of blinding ....................................................................................................................... 33 
6.9.2. 
Unblinding the study medication ...................................................................................................... 33 
7. 
STUDY ASSESSMENTS ......................................................................................................................... 33 
7.1. 
Effectiveness Evaluations ...................................................................................................................... 34 
7.1.1. 
Clinician’s Eyebrow Assessment (CEA) ......................................................................................... 34 
7.1.2. 
Subject’s Eyebrow Assessment (SEA) ............................................................................................. 35 
7.1.3. 
Subject Eyebrow Satisfaction (SES) ................................................................................................ 36 
7.2. 
Safety Evaluations ................................................................................................................................... 36 
7.2.1. 
ECGs ........................................................................................................................................................ 36 
7.2.2. 
Brief physical examination ................................................................................................................. 37 
7.2.3. 
Vital signs ............................................................................................................................................... 37 
7.2.4. 
Clinical laboratory sampling ............................................................................................................. 38 
7.2.5. 
Local Tolerability Assessment (LTA) .............................................................................................. 39 
7.2.6. 
Urine Pregnancy tests .......................................................................................................................... 41 
7.3. 
Other Evaluations ................................................................................................................................... 41 
7.3.1. 
Demographics, medical history and alopecia areata history ..................................................... 41 
7.3.2. 
Standardized photography ................................................................................................................. 42 
8. 
ADVERSE EVENTS ................................................................................................................................. 42 
8.1. 
Definitions ................................................................................................................................................. 42 
8.1.1. 
Adverse events (AE) ............................................................................................................................. 42 
8.1.2. 
Serious adverse event (SAE) .............................................................................................................. 43 
8.1.3. 
Adverse event reporting period ......................................................................................................... 43 
8.1.4. 
Severity .................................................................................................................................................... 44 


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8.1.5. 
Relationship to study medication ...................................................................................................... 44 
8.2. 
Reporting Procedures ............................................................................................................................. 44 
8.2.1. 
Procedures for reporting adverse events ........................................................................................ 44 
8.2.2. 
Procedure for reporting a serious adverse event .......................................................................... 45 
8.2.3. 
Safety Monitoring ECG Discontinuation Criteria ....................................................................... 45 
8.2.4. 
Study Medication Interruption and Discontinuation .................................................................. 46 
8.2.4.1 
Study Medication Interruption.................................................................................................................. 46 
8.2.4.2 
Study Medication Discontinuation ........................................................................................................... 47 
9. 
PREGNANCY ............................................................................................................................................. 47 
9.1. 
Definition of Women of Child Bearing Potential (WOCBP) ........................................................ 47 
9.2. 
Highly Effective Methods of Birth Control ....................................................................................... 47 
10. 
STATISTICAL ANALYSES ................................................................................................................... 49 
10.1. 
Statistical Methods .................................................................................................................................. 49 
10.2. 
Sample Size ............................................................................................................................................... 50 
11. 
TRAINING, MONITORING, DATA MANAGEMENT AND QUALITY 
ASSURANCE .............................................................................................................................................. 50 
11.1. 
Training ..................................................................................................................................................... 50 
11.2. 
Monitoring ................................................................................................................................................ 50 
11.3. 
Data Management ................................................................................................................................... 51 
11.4. 
Quality Assurance ................................................................................................................................... 51 
12. 
ETHICS AND GENERAL STUDY CONDUCT CONSIDERATIONS ....................................... 51 
12.1. 
Institutional Review Board (IRB)/Ethics Committee (EC) ........................................................... 51 
12.2. 
Ethical Conduct of the Study ................................................................................................................ 51 
12.3. 
Subject Information and Consent ....................................................................................................... 52 
12.4. 
Study Conduct and Protocol Amendments ....................................................................................... 52 
12.5. 
Regulatory Documents ........................................................................................................................... 52 
12.6. 
Contractual Requirements .................................................................................................................... 52 
12.7. 
Data Collection and Archiving ............................................................................................................. 53 
12.7.1. 
Data collection ....................................................................................................................................... 53 
12.7.2. 
Source documentation ......................................................................................................................... 53 
12.7.3. 
Archiving ................................................................................................................................................ 53 
13. 
References .................................................................................................................................................... 54 
14. 
APPENDIX A:  PARTICIPANT INSTRUCTION SHEET ............................................................ 56 


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1. 
SYNOPSIS 
Protocol Number:                  ATI-50002-AAB-201 
Protocol Title: 
An Open-Label Pilot Study of the Safety, Tolerability and 
Efficacy of ATI-50002 Topical Solution Administered Twice-
Daily in Adult Subjects with Eyebrow Loss due to Alopecia 
Areata, Alopecia Universalis or Alopecia Totalis 
Sponsor:  
Phase of Development: 
Aclaris Therapeutics, Inc. 
Phase 2 
Study Drug Description: 
ATI-50002 Topical Solution 0.46% 
Study Objective: 
The main objective of this study is to assess the safety, tolerability and efficacy of ATI-50002 
Topical Solution 0.46% in subjects with unilateral or bilateral loss of eyebrow hair due to 
alopecia areata (AA), alopecia universalis (AU) or alopecia totalis (AT). 
 
Study Design: 
This is an open-label study which will be conducted at 1 to 2 sites.   
 
Subjects will be required to have a clinical diagnosis of AA, AU or AT with unilateral or 
bilateral loss of eyebrow hair with a duration of the current episode of at least 6 months, but 
not more than seven years. A total of approximately 12 subjects will apply ATI-50002 Topical 
Solution 0.46%, to the affected eyebrow(s) twice-daily (BID) for 24 weeks. 
 
After completing Visit 1 (start of the screening period), subjects will be assessed for eligibility 
to receive study medication.   
 
Subjects will apply study medication to the entire affected eyebrow(s), twice-daily for 24 
weeks. The 24-week treatment period will be followed by a 4-week no-treatment follow-up 
period. Assessment of response to treatment will be performed at Week 4, Week 8, Week 12, 
Week 16, Week 20, Week 24 and Week 28.   
 
Safety and tolerability will be evaluated throughout the study by assessment of electro-
cardiograms (ECG), clinical laboratory tests, adverse events and vital signs. 
 
The duration of the study participation is anticipated to be a maximum of 233 days (an up to 28-
day screening period, a 169-day treatment period with a 4-day window, a 28-day no-treatment 
follow-up period with a window of 4 days). 
 
Study visits are: 
 Visit 1 (Day -28 to 0): screening; start eligibility assessment period 
 Visit 2 (Week 0): initiation of twice-daily study medication application


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 Visits 3-10 (Weeks 1-24): treatment period 
 Visit 11 (Week 28): no-treatment period follow-up; end of study 
Number of Subjects to be Enrolled: 
Approximately 12 subjects will be enrolled in this study.  
Number of Study Sites: 
This study will be conducted at up to 2 sites in the US. 
Inclusion Criteria: 
To be eligible for the study, subjects must fulfill all the following criteria: 
1. Subject is at least 18 years of age. 
2. Subject has, based on a subject history and clinical examination, a clinical diagnosis of 
AA, AU or AT with no eyebrow hair in the affected area(s) and no eyebrow regrowth 
over the previous 6 months.  Affected area is defined as the area(s) of eyebrow hair 
loss identified at Baseline. 
3. Subject has a Clinician Eyebrow Assessment score of 0 (No eyebrow hair in the 
affected area) for at least one eyebrow.   
4. Subject has a Subject Eyebrow Assessment score of 0 (No eyebrow hair in the affected 
area) for at least one eyebrow.   
5. Subject has a duration of the current episode of AA, AU or AT with unilateral or 
bilateral loss of eyebrow hairs (with at least one distinct patch of >30% loss of 
eyebrow hair) for at least 6 months and no more than seven years prior to Visit 1.  
6. Subjects who are Women of Childbearing Potential (WOCBP) must have a negative 
serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and 
agree to use a highly effective method of birth control for the duration of the study and 
for 30 days after last study medication application. 
7. Subject is non-pregnant and non-lactating and not planning a pregnancy during the 
duration of the study and for 30 days after the last study medication application.  
8. Subject is in good general health and free of any known disease state or physical 
condition which, in the opinion of the investigator, would interfere with the study 
requirements or put the subject at undue risk by study participation. 
9. Subject is willing and able to follow all study instructions and to attend all study visits. 
10. Subjects taking hormonal replacement therapy must have been on the same dose for at 
least 6 months prior to Visit 1 and must agree to maintain the same dose for the 
duration of the study and for 90 days after the last study medication application. 
11. Subjects taking thyroid replacement therapy must have been on the same dose for at 
least 6 months prior to Visit 1 and must agree to maintain the same dose for the 
duration of the study. 
12. Subject agrees to refrain from any eyebrow removal (e.g.¸ plucking, threading, etc.) for 
the duration of the study.


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13. Subject agrees to refrain from any cosmetic surgery (e.g., piercing, tattooing, etc.), on 
the treatment areas, for the duration of the study. 
14. Subject can comprehend and is willing to sign an Informed Consent Form (ICF). 
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: 
Any subject who meets one or more of the following criteria will not be included in this study: 
1) Subject has, in the opinion of the investigator, permanent eyebrow loss attributed to causes 
other than AA, AU or AT such as overgrooming, or scarring hair loss. 
2) Subject currently has, or has a history of, skin disease in the eyebrow area (e.g., psoriasis, 
seborrheic dermatitis, etc.) that, in the opinion of the investigator, would interfere with the 
study medication application or study assessments. 
3) Subject currently has, or has a history of, severe, progressive or uncontrolled autoimmune, 
metabolic, endocrinologic, renal, hepatic, gastrointestinal, pulmonary, cardiovascular, 
genitourinary (i.e., renal disease), hematological disease, neurologic or cerebral disorders, 
infectious disease or coagulation disorders that, in the opinion of the investigator, put the 
subject at undue risk by study participation. 
4) Subject currently has, or has a history of, proven or suspected systemic or cutaneous 
malignancy and /or lymphoproliferative disease, other than a history of adequately treated, 
well healed and completely cleared non-melanoma skin cancers (e.g. basal or squamous 
cell carcinoma) treated successfully at least one year prior to Visit 1.   
5) Subject currently has evidence of active or latent bacterial infection, including tuberculosis, 
or viral infections at the time of enrollment or a history of incompletely treated or untreated 
tuberculosis.  Subjects who have completed therapy for latent tuberculosis may participate.  
6) Subject has a history of serious local infection (e.g., cellulitis, abscess) or a systemic 
infection, including but not limited to, pneumonia or septicemia, within 12 weeks prior to 
Visit 1.  Subjects on an antibiotic for a nonserious, acute local infection must complete the 
antibiotic course prior to enrollment in the study.  
7) Subjects positive for HIV, Hepatitis B or C.  Subjects with serologic evidence of Hepatitis 
B vaccination (HepB surface Ab without the presence of HepB surface Ag) will be allowed 
to participate. 
8) Subject currently has or has a known history of herpes zoster or cytomegalovirus (CMV) 
within 8 weeks prior to Visit 1.    
9) Subject has a history of frequent outbreaks of Herpes Simplex Virus defined as 4 or more 
episodes per year. 
10) Subject has any history of eyebrow tattooing, or microblading that in the opinion of the 
investigator would interfere with the assessment of safety or efficacy. 
11) Subject has used any semi-permanent eyebrow coloring (e.g., tinting, dying, etc.) within 6 
months prior to Visit 1 that in the opinion of the investigator would interfere with the 
assessment of safety or efficacy.


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12) Clinically significant laboratory abnormalities at Screening that, in the opinion of the 
Investigator, would make the subject a poor candidate for the study.   
13) Subjects with absolute neutrophil count <1,000/mm3, or platelet count <50,000/ml. 
14) Subject used any of the following therapies within the specified period prior to Visit 1: 
Systemic therapies: 
 Disease Modifying Anti-Rheumatic Drugs (DMARDS), Biologics or 
immunosuppressants, such as: anakinra, adalimumab, azathioprine, 
glucocorticosteroids, cyclosporine, etanercept, infliximab, methotrexate, TNF 
inhibitors, ustekinumab, secukinumab, ixekizumab, certolizumab pegol: 4 
weeks or 5 half-lives whichever is longer 
 Oral retinoids: 12 weeks 
 Plaquenil: 8 weeks 
 JAK inhibitors (oral or topical): 1 year 
 Intralesional steroids on the eyebrow area: 4 weeks 
Topical therapies on the eyebrow area: 
 Phototherapy, Laser Therapy: 12 weeks 
 Anthralin, bimatoprost, glucocorticosteroids, diphencyprone, diphenylcycloprophenone 
(DPCP), Squaric acid dibutyl ester (SADBE), minoxidil, pimecrolimus, tacrolimus: 4 
weeks 
 Topical treatments (prescription and over-the-counter) that contain retinoids, retinol, 
alpha hydroxy acids (e.g. glycolic, lactic acids) and beta hydroxy acids (e.g. salicylic 
acid) on and around the eyebrow area: 4 weeks 
15) Subject has a history of sensitivity to any of the ingredients in the study medication. 
16) Subject has participated in an investigational drug or device trial in which administration of 
an investigational study drug or device occurred within 30 days or 5 half-lives (whichever 
is longer) prior to Visit 1.  Subjects who have participated in a study of an investigational 
drug, device or biologic agent for alopecia areata (AA, AU or AT) within 1 year of screening 
will be eligible to participate only with individual permission from the Medical Monitor. 
17) History of or current alcohol or drug abuse within 2 years of assessment for study enrollment. 
18) Screening ECG findings of: 
 QTcF >450msec for males or >470msec for females (use of the ECG algorithm is 
acceptable for this purpose) 
 Heart rate < 45 or > 100 beats/minutes (inclusive) 
 Rhythm disturbance other than sinus arrhythmia or ectopic supraventricular rhythm 
(ectopic atrial rhythm) 
 Conduction disturbance including PR >240msec, pre-excitation (delta wave and PR 
<120msec), second degree or higher AV block 
 Acute or chronic signs of ischemia  
 Left Bundle Branch Block 
 Prior myocardial infarction 


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Criteria for Evaluation: 
Efficacy: 
The investigator will evaluate the severity of eyebrow loss using the Clinician’s Eyebrow 
Assessment. Subjects will evaluate the severity of eyebrow loss using the Subject’s Eyebrow 
Assessment. 
 
Safety: 
The investigator will assess clinical laboratory safety tests, vital sign readings, concomitant 
therapies, urine pregnancy test results, and adverse event (AE) information throughout the study. 
 
Other: 
Subjects will assess their satisfaction with the status of each eyebrow using the Subject Eyebrow 
Satisfaction scale. Standardized color photographs to assist with documenting the status of the 
subject’s eyebrows will be taken throughout the study. 
Study Drug Administration: 
Subjects will apply ATI-50002 Topical Solution 0.46% BID for 24 weeks to the affected 
eyebrow(s).  At Visit 2 (Baseline), after confirmation of the inclusion and exclusion criteria, an 
investigational staff member will instruct the subject on the proper study medication application 
technique, observe the first study medication application and monitor the subject for at least 20 
minutes after the application. The subject will then start a 24-week treatment period. 
 
Statistical Methods: 
Summary descriptive statistics (N, mean, median, SD) by visit will be provided for all safety 
and efficacy parameters.  Primary and secondary efficacy parameters are described below: 
 
Mean change from baseline in eyebrow growth will be calculated as the mean change in the 
Clinician’s Eyebrow Assessment (CEA) from Visit 2 (Baseline) compared to end of treatment 
(Visit 10). The CEA evaluates eyebrows on a scale from “No eyebrow hair” (grade 0) to “Full 
eyebrow hair” (grade 4).     
 
Mean change from baseline in the Subject’s Eyebrow Assessment (SEA) will be calculated from 
Visit 2 (Baseline) to end of treatment (Visit 10). 
 
Mean change from baseline in the Subject’s Eyebrow Satisfaction (SES) will be calculated from 
Visit 2 (Baseline) to end of treatment (Visit 10). 
 
All efficacy summaries will be based on the per-protocol population including all subjects who 
have Baseline (Visit 2) and Visit 10 efficacy data and no major protocol violations. 
 
Safety analyses will include descriptive statistics calculated on the safety parameters using the 
safety population. The proportion of subjects with treatment-emergent adverse events will be 
tabulated and presented by Medical Dictionary for Regulatory Activities (MedDRA) System 
Organ Class. Vital signs and clinically significant abnormal laboratory results will also be 


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tabulated and presented. Change from Baseline in the Local Tolerability Assessments (LTA) 
to end of treatment (Visit 10) will be summarized.  
 
Data from all enrolled and treated subjects will be presented and summarized. Safety summaries 
will include listings of adverse events incidences within each MedDRA System Organ Class, 
and changes from pre-application values in vital signs. Adverse event summaries will be 
presented by study medication showing the proportion of subjects experiencing adverse events, 
both overall and by MedDRA System Organ Class. 
 
 


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2. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Term 
AA
Alopecia Areata
AE 
Adverse Event
ALT
Alanine aminotransferase
ANCOVA
Analysis of Covariance
ANOVA
Analysis of Variance
AST
Aspartate aminotransferase
AT
Alopecia Totalis
AU
Alopecia Universalis
BID
Twice-daily
BUN
Blood Urea Nitrogen
°C
Degrees Centigrade
CD
Cluster of Differentiation
CEA
Clinician’s Eyebrow Assessment
CMV
Cytomegalovirus
CRA
Clinical Research Associate
CRF
Case Report Form
CS
Clinically Significant
DMARDS
Disease modifying anti-rheumatic drugs
DPCP
Diphenylcycloprophenone
e.g. 
for example (Latin; exempla gratia)
EC
Ethics Committee
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EHL
Eyebrow Hair Loss
°F
Degrees Fahrenheit
FDA
Food and Drug Administration
G
Gram
GCP
Good Clinical Practice
HEENT
Head, Eye, Ear, Nose and Throat
HIPAA
Health Insurance Portability and Accountability Act of 1996
HIV
Human Immunodeficiency Virus
IB
Investigator’s Brochure
ICF
Informed Consent Form


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Abbreviation 
Term 
ICH
International Conference on Harmonization 
i.e. 
that is (Latin; id est)
IFN
Interferon
IL
Interleukin
IRB
Institutional Review Board
IUD
Intrauterine Device
IUS
Intrauterine Hormone Releasing System
JAK
Janus Kinase
LDH
Lactate Dehydrogenase
LTA
Local Tolerability Assessment
LOCF
Last Observation Carried Forward
MedDRA
Medical Dictionary for Regulatory Activities
MHC
Major Histocompatibility Complex
ml
Milliliter
Mm
Millimeter
NCS
Not Clinically Significant
NK/ NKG
Natural Killer/ Natural Killer Group
OTC
Over-The-Counter
PDT
Photodynamic Therapy
PUVA
Psoralen and Ultraviolet A
SADBE
Squaric acid dibutyl ester
SAE
Serious Adverse Event
SEA
Subject’s Eyebrow Assessment
SES
Subject’s Eyebrow Satisfaction
SI
Subject Identifier
SOP
Standard Operation Procedure
STAT
Signal Transducer and Activator of Transcription
TEAE
Treatment Emergent Adverse Event
Tyk2
Tyrosine Kinase 2
UPT
Urine Pregnancy Test
US
United States
UVA
Ultraviolet A 
UVB
Ultraviolet B
WOCBP
Women of childbearing potential


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3. 
INTRODUCTION 
Aclaris Therapeutics, Inc. is developing ATI-50002 Topical Solution for the treatment of alopecia 
areata.  ATI-50002 is a potent, highly selective inhibitor of Janus kinase 1 (JAK 1) and Janus 
kinase 3 (JAK 3). 
 
3.1. 
Summary 
Overview of Alopecia Areata 
Alopecia areata (AA) is an autoimmune dermatologic condition which in its mildest form is 
typically characterized by patchy non-scarring hair loss on the scalp and/or body. More severe 
forms of AA include total scalp hair loss, known as alopecia totalis (AT), and total loss of all the 
hair on the scalp and body, importantly, including loss of eyebrows, eyelashes, and intranasal hair- 
known as alopecia universalis (AU). While spontaneous regrowth of hair is common in the milder 
form of AA (patchy), where the hair loss may wax and wane, in patients with the extensive hair 
loss of AT or AU, spontaneous hair regrowth is rare. AA affects both males and females across all 
ethnic groups and is the most prevalent autoimmune disease in the United States, with a lifetime 
risk of 1.7% (Safavi 1995). About two-thirds of affected individuals are 30 years old or younger 
at the time of disease onset.  
 
The course of AA is unpredictable and while up to 50% of patients may recover within 1 year even 
without treatment, most patients will have more than one episode of hair loss (Price 2008). Factors 
portending a poorer prognosis for regrowth are: more extensive hair loss presentations (extensive 
AA, AT, AU), an ophiasis pattern of hair loss, a long duration of hair loss, a positive family history, 
the presence of other autoimmune diseases, nail involvement, and young age of first onset (Tosti 
2006, Weise 1996). In children, the disease may have a tendency towards worsening with time, 
even if the initial presentation was mild and the progressively disfiguring nature of the disease can 
be psychologically devastating. AA is highly associated with numerous psychiatric comorbidities 
including adjustment disorders, anxiety disorders and depression in both children and adults, and 
an effective treatment for AT and AU, the more severe forms of the disease, represents a significant 
unmet medical need (Bilgic 2014, Ruiz-Doblado 2003, Alkhalifah 2010).  
 
The clinical development of innovative therapies in AA has lagged far behind other autoimmune 
conditions and there are currently no evidence-based treatments for AA. A Cochrane database 
review highlighted that few therapies for AA have been comprehensively evaluated in randomized 
clinical trials and that no treatment has demonstrated significant benefit compared to placebo 
according to evidence-based assessment (Delamere, 2008). This lack of good evidence-based data 
remains a challenge for physicians attempting to select efficacious treatments for their patients 
and, as a result, numerous approaches to treatment exist and are typically based on considerations 
such as the age of the patient, the extent and/or duration of the disease, patient expectations, cost 
considerations (both time and financial resources) and physician preferences and experience. 
 
Common treatments for the less severe (patchy) form of AA include corticosteroids, either 
topically applied or injected intralesionally into the alopecic areas, or the induction of an allergic 
reaction at the site of hair loss using a topical contact sensitizing agent - an approach known as 


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topical immunotherapy, typically with the topical contact sensitizers diphenylcycloprophenone 
(DPCP), squaric acid dibutyl ester (SADBE), or treatment with topical anthralin. While these same 
treatment options may be utilized for the more severe forms of AA, their use in the more severe 
forms of AA is limited not only due to limited efficacy, but also because of the impracticality of 
using them over extensive body surface areas. Additional treatments used for extensive forms of 
AA (AT, AU), have included systemic steroids (pulsed or chronically administered), 
immunosuppressive agents such as cyclosporine or methotrexate, phototherapy with psoralen 
+UVA (PUVA), narrow-band UVB, photodynamic therapy (PDT), laser therapy (e.g., excimer 
laser, fractional photothermolysis lasers), prostaglandin analogs, etanercept, bexarotene and 
others, all with varying degrees of success and each with its inherent risk of adverse effects and 
unproven efficacy (Alkhalifah 2010, Price 1999, Hordinsky 2015, Strober 2005). Most recently, 
however, a breakthrough in the understanding of the pathophysiology of AA and several case 
reports in the literature have suggested that a group of inhibitors of the JAK-STAT pathway, the 
Janus Kinase (JAK) inhibitors, or “jakinibs” may be efficacious in the treatment of AA even in its 
most severe phenotypes, AT and AU (Jabbari, 2015, Pieri, 2015, Xing 2014).  
 
The JAKs, are members of a family of tyrosine kinases that are involved in cytokine receptor 
signaling. The JAK family of enzymes (JAK1, JAK2, JAK3, Tyk2) plays an essential role in 
regulating the signaling process of most cytokines in cells by linking the cytokine induced 
signaling from the cell surface membrane receptors to signal transducers and activators of 
transcription, or STATs, within the cells. Once these JAK receptors are activated by the binding 
of a cytokine to the appropriate receptor, they initiate a JAK-STAT signaling pathway which can 
modify gene expression and modulate important regulatory functions in the cell, including 
regulating immune and inflammatory responses. JAK1 and JAK3 are constitutively associated 
with the alpha chain and the common gamma chain (γc), respectively, of the receptors for 
interleukin-2 (IL2), interleukin-4 (IL-4), interleukin-7 (IL-7) interleukin-9 (IL-9), interleukin-15 
(IL-15), and interleukin-21 (IL-21). When these cytokines bind to their respective receptors, JAK1 
and JAK3 are activated and initiate a signaling cascade that drives key inflammatory events, 
including lymphocyte activation and proliferation. The JAK inhibitors can block the cytokine 
receptor signaling pathways, (in this instance JAK1 and JAK3) blocking JAK-STAT transcription 
activation, and can therefore modulate inflammatory or immune responses, which can be 
beneficial in a variety of disease states, particularly, as recently reported, AA (Xing 2014). In that 
report, pharmacologic inhibition of JAK kinase signaling (JAK-STAT signaling) was reported to 
promote hair growth in both genetic mouse models of alopecia and in human subjects. 
 
Immunopathology & Pathophysiology of AA 
AA results from an autoimmune attack on the hair follicles that results in growing anagen-phase 
terminal hairs being induced to prematurely enter the telogen-phase and then shed. In its most 
acute state, AA demonstrates a histopathologically characteristic white cell infiltrate, the so called 
“swarm of bees”, encircling the human hair follicle, though more chronic forms typically 
demonstrate a more sparse infiltrate (Jabbari 2016, Whiting 2003). Though the exact autoantigens 
expressed in the perifollicular epithelium that allow these specific T-cells to infiltrate the normally 
immunologically privileged hair follicle have been unknown, the T-cells that home to the hair 
follicle have been demonstrated to consist of both CD4 and CD8 cells. Most recent studies have 
further characterized a specific subpopulation of activated NKG2D-bearing CD8 T cells as being 


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prominent in the peribulbar infiltrate, and it is now currently felt that these CD8+NKG2D+ effector 
T cells preferentially localize to dermal sheath cells aberrantly expressing high levels of MHC 
molecules and NKG2D ligands. Interferons, as key activators of the MHC locus and of the cellular 
immune response, appear to play a key role in eliminating the immunologic privilege of the hair 
follicle and in inducing and maintaining the pathologic inflammatory response in AA. This is also 
seen in the C3H-HeJ mouse model of AA, in which IFN-γ is required for pathogenesis, and in 
which administration of IFN-γ accelerates disease (Gilhar 2005, Hirota 2003). 
 
AA has been viewed as a Th1-driven disease and, consistent with a pathogenic cellular immune 
response, elevated Th1 cytokines/ chemokines (IFN-induced chemokines [IP-10/CXCL10]) are 
seen in the peripheral blood of AA patients and IFN-inducible gene signatures have been described 
in the skin of AA patients and may correlate with disease activity (Arca 2004, Barahmani 2009, 
Kuwano 2007). Additionally, transcriptional profiles in human AA patients have shown a Type I 
IFN response in lesional biopsies and Th1 skewing and elevated IFN response 
cytokines/chemokines in both the peripheral blood and in reviewed scalp biopsies (Jabbari 2015, 
Xing 2014, Jabbari 2016). The cellular source of IFN-γ is hypothesized to be the T cells as in the 
AA mouse model IFN-gamma producing CD8+NKG2D+ cells dominate the dermal hair follicle 
infiltrate, and in human AA, IFN-γ producing cells were identified in 4 of 5 dermal crawl-out 
assays (Christiano 2016). Additionally, data implicate IL-15 in driving activation of IFN-
producing CD8 T cells (Xing 2014).  
 
Thus, preclinical and preliminary clinical information, as discussed above, strongly suggests that 
the primary pathophysiologic mechanism in AA (including AT and AU) is a cytokine mediated 
(primarily through T-lymphocyte induced upregulation of IL-15 and IFN gamma) induction of and 
prolonged maintenance of the telogen stage of the hair cycle. Inhibitors of the JAK/STAT pathway, 
particularly JAK1 and JAK3, are known to downregulate the effects of both IFN-gamma (through 
the inhibition at JAK1), and IL-15 (through inhibition at both JAK1 and JAK 3), and several 
published case reports have demonstrated the potential for compounds that are JAK1/3 inhibitors 
to induce hair growth in patients with AA (Kim 2017, Craiglow, 2014, Gupta 2016, Scheinberg 
2016). As ATI-50002 is a potent inhibitor at JAK 1 and JAK 3, it is strongly suggested that ATI-
50002 may be effective in the treatment of AA. 
 
Among patients with AA, patients with higher disease burdens are unlikely to have satisfactory 
outcomes with current therapies. Aclaris Therapeutics, Inc. is developing ATI-50002 as a topical 
treatment for stable AA. Aclaris is also developing ATI-50001 for the treatment of AU and AT. 
ATI-50001 is a prodrug that is rapidly converted pre-systemically to ATI-50002, a potent highly 
selective inhibitor of Janus kinase 1 (JAK1) and Janus kinase 3 (JAK3). In this study, we will be 
looking to see if topical application of the JAK1/JAK3 inhibitor, ATI-50002, will result in 
regrowth of eyebrows in areas of loss due to AA, AU or AT. 
 
In a previous Phase 1 study in healthy volunteers, single ascending oral doses of ATI-50001, 50 
mg to 500 mg and multiple ascending doses of up to 400 mg BID were well-tolerated. There were 
no SAEs. All treatment emergent adverse events (TEAEs) were transient and mild in intensity with 
the exception of 4 TEAEs: facial bone fracture, headache (2), and catheter site pain which were 
classified as moderate. The most frequently reported drug related TEAEs occurring in >5% 


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subjects were abdominal pain (10%), flatulence (7%), diarrhea (6%) and headache (6%). Three 
subjects showed mildly elevated ALT or AST concentrations that were considered not clinically 
significant. No clinically significant laboratory abnormalities were observed. There were no 
clinically significant findings from 12-lead ECGs or vital signs assessments.   
 
ATI-50001 was not detected in plasma and there was a dose related increase in plasma of the active 
metabolite ATI-50002. The half-life of ATI-50002 after 14 days of dosing was approximately 9.0 
hours. Systemic levels of ATI-50002, following oral doses of ATI-50001 in healthy volunteers 
transiently reduced pSTAT5 activity in ex vivo IL-2 stimulated lymphocytes, indicating inhibition 
of the JAK signaling pathway. Upon multiple dosing, pSTAT5 activity showed a more sustained 
inhibition during the dosing period.   
 
Non-clinical studies conducted with oral administration of ATI-50001 and topical administration 
of ATI-50002 support the topical administration of ATI-50002 (ATI-50002 Topical Solution 
Investigator Brochure August 2017).   
 
3.2. 
Study Rationale 
Preclinical and preliminary clinical information, as discussed above, strongly suggests that the 
primary pathophysiologic mechanism in AA (including AT and AU) is a cytokine mediated 
(primarily through T-lymphocyte induced upregulation of IL-15 and IFN gamma) induction of and 
prolonged maintenance of the telogen stage of the hair cycle. Inhibitors of the JAK/STAT pathway, 
particularly JAK1 and JAK3, are known to downregulate the effects of both IFN-gamma (through 
the inhibition at JAK1), and IL-15 (through inhibition at both JAK1 and JAK 3), and several 
published case reports have demonstrated the potential for compounds that are JAK1/3 inhibitors 
to induce hair growth in patients with AA. As ATI-50002 is a potent inhibitor at JAK 1 and JAK 
3, it is strongly suggested that ATI-50002 may be effective in the treatment of AA.   
 
The purpose of this proof of concept study is to demonstrate the safety, tolerability and efficacy of 
ATI-50002 Topical Solution, a topical Janus kinase (JAK 1/3) inhibitor in the treatment of 
unilateral or bilateral loss of eyebrow hair in subjects with AA, AT and AU.   
 
4. 
STUDY OBJECTIVES 
The main objective of this study is to assess the safety, tolerability and efficacy of ATI-50002 
Topical Solution 0.46% in subjects with unilateral or bilateral loss of eyebrow hair due to AA, AU 
or AT. 
 
5. 
SELECTION AND DISPOSITION OF STUDY POPULATION 
5.1. 
Number of Subjects 
Approximately 12 subjects will be enrolled at 1 to 2 sites in the United States. 
 


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5.2. 
Study Population Characteristics 
Male and female subjects, 18 years of age or older, with a clinical diagnosis of unilateral or bilateral 
loss of eyebrow hair due to AA, AU or AT, who meet all the inclusion criteria and none of the 
exclusion criteria will be eligible to enroll in this study. 
 
5.3. 
Inclusion Criteria 
To be eligible for the study, subjects must fulfill all the following criteria: 
1. Subject is at least 18 years of age. 
2. Subject has, based on a subject history and clinical examination, a clinical diagnosis of 
AA, AU or AT with no eyebrow hair in the affected area(s) and no eyebrow regrowth 
over the previous 6 months.  Affected area is defined as the area(s) of eyebrow hair loss 
identified at Baseline. 
3. Subject has a Clinician Eyebrow Assessment score of 0 (No eyebrow hair in the affected 
area) for at least one eyebrow.   
4. Subject has a Subject Eyebrow Assessment score of 0 (No eyebrow hair in the affected 
area) for a least one eyebrow. 
5. Subject has a duration of the current episode of AA, AU or AT with unilateral or bilateral 
loss of eyebrow hairs (with at least one distinct patch of >30% loss of eyebrow hair) for 
at least 6 months and no more than seven years prior to Visit 1.  
6. Subjects who are Women of Childbearing Potential (WOCBP) must have a negative 
serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and 
agree to use a highly effective method of birth control for the duration of the study and 
for 30 days after last study medication application. 
7. Subject is non-pregnant and non-lactating and not planning a pregnancy during the duration 
of the study and for 30 days after the last study medication application.  
8. Subject is in good general health and free of any known disease state or physical 
condition which, in the opinion of the investigator, would interfere with the study 
requirements or put the subject at undue risk by study participation. 
9. Subject is willing and able to follow all study instructions and to attend all study visits. 
10. Subjects taking hormonal replacement therapy must have been on the same dose for at 
least 6 months prior to Visit 1 and must agree to maintain the same dose for the duration 
of the study and for 90 days after the last study medication application. 
11. Subjects taking thyroid replacement therapy must have been on the same dose for at least 
6 months prior to Visit 1 and must agree to maintain the same dose for the duration of the 
study. 
12. Subject agrees to refrain from any eyebrow removal (e.g.¸ plucking, threading, etc.) for 
the duration of the study. 
13. Subject agrees to refrain from any cosmetic surgery (e.g., piercing, tattooing, etc.), on the 
treatment areas, for the duration of the study. 
14. Subject can comprehend and is willing to sign an Informed Consent Form (ICF). 
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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5.4. 
Exclusion Criteria 
Any subject who meets one or more of the following criteria will not be included in this study:  
1. Subject has, in the opinion of the investigator, permanent eyebrow loss attributed to 
causes other than AA, AU or AT such as overgrooming, or scarring hair loss. 
2. Subject currently has, or has a history of, skin disease in the eyebrow area (e.g., psoriasis, 
seborrheic dermatitis, etc.) that, in the opinion of the investigator, would interfere with 
the study medication application or study assessments. 
3. Subject has, or has a history of, severe, progressive or uncontrolled autoimmune, 
metabolic, endocrinologic, renal, hepatic, gastrointestinal, pulmonary, cardiovascular, 
genitourinary (i.e., renal disease), hematological disease, neurologic or cerebral disorders, 
infectious disease or coagulation disorders that, in the opinion of the investigator, would 
put the subject at undue risk by study participation. 
4. Subject currently has, or has a history of, proven or suspected systemic or cutaneous 
malignancy and /or lymphoproliferative disease, other than a history of adequately 
treated, well healed and completely cleared non-melanoma skin cancers (basal or 
squamous cell carcinoma) treated successfully at least one year prior to Visit 1.   
5. Subject currently has evidence of active or latent bacterial infection, including 
tuberculosis, or viral infections at the time of enrollment or a history of incompletely 
treated or untreated tuberculosis.  Subjects who have completed therapy for latent 
tuberculosis may participate.    
6. Subject has a history of serious local infection (e.g., cellulitis, abscess) or a systemic 
infection including but not limited to, pneumonia or septicemia, within 12 weeks prior to 
Visit 1.  Subjects on an antibiotic for a nonserious, acute local infection must complete 
the antibiotic course prior to enrollment in the study.  
7. Subjects positive for HIV, Hepatitis B or C.  Subjects with serologic evidence of 
Hepatitis B vaccination (HepB surface Ab without the presence of HepB surface Ag) will 
be allowed to participate. 
8. Subject currently has or has a known history of herpes zoster or cytomegalovirus (CMV) 
within 8 weeks prior to Visit 1.    
9. Subject has a history of frequent outbreaks of Herpes Simplex Virus, defined as 4 or 
more episodes per year. 
10. Subject has any history of eyebrow tattooing, microblading that in the opinion of the 
investigator would interfere with the assessment of safety or efficacy. 
11. Subject has used any semi-permanent eyebrow coloring (e.g., tinting, dying, etc.) within 
6 months prior to Visit 1 that in the opinion of the investigator would interfere with the 
assessment of safety or efficacy. 
12. Clinically significant laboratory abnormalities at Screening that, in the opinion of the 
Investigator, would make the subject a poor candidate for the study.   
13. Subjects with absolute neutrophil count <1,000/mm3, or platelet count <50,000/ml. 
14. Subject used any of the following therapies within the specified period prior to Visit 1: 
Systemic therapies: 


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 Disease Modifying Anti-Rheumatic Drugs (DMARDS), Biologics or 
immunosuppressants, such as: anakinra, adalimumab, azathioprine, 
glucocorticosteroids, cyclosporine, etanercept, infliximab, methotrexate, 
TNF inhibitors, ustekinumab, secukinumab, ixekizumab, certolizumab 
pegol: 4 weeks or 5 half-lives whichever is longer 
 Oral retinoids: 12 weeks 
 Plaquenil: 8 weeks 
 JAK inhibitors (oral or topical): 1 year 
 Intralesional steroids on the eyebrow area: 4 weeks 
Topical therapies on the eyebrow area: 
 Phototherapy, Laser Therapy: 12 weeks 
 Anthralin, bimatoprost, glucocorticosteroids, diphencyprone, 
diphenylcycloprophenone (DPCP), Squaric acid dibutyl ester (SADBE), 
minoxidil, pimecrolimus, tacrolimus: 4 weeks 
 Topical treatments (prescription and over-the-counter) that contain 
retinoids, retinol, alpha hydroxy acids (e.g. glycolic, lactic acids) and beta 
hydroxy acids (e.g. salicylic acid) on and around the eyebrow area: 4 
weeks 
15. Subject has history of sensitivity to any of the ingredients in the study medication. 
16. Subject has participated in an investigational drug or device trial in which administration 
of an investigational study drug or device occurred within 30 days or 5 half-lives 
(whichever is longer) prior to Visit 1.  Subjects who have participated in a study of an 
investigational drug, device or biologic agent for alopecia areata (AA, AU or AT) within 
1 year of screening will be eligible to participate only with individual permission from 
the Medical Monitor. 
17. History of or current alcohol or drug abuse within 2 years of assessment for study 
enrollment. 
18. Screening ECG findings of: 
 QTcF >450msec for males or >470msec for females (use of the ECG algorithm is 
acceptable for this purpose) 
 Heart rate < 45 or > 100 beats/minutes (inclusive) 
 Rhythm disturbance other than sinus arrhythmia or ectopic supraventricular 
rhythm (ectopic atrial rhythm) 
 Conduction disturbance including PR >240msec, pre-excitation (delta wave and 
PR <120msec), second degree or higher AV block 
 Acute or chronic signs of ischemia  
 Left Bundle Branch Block 
 Prior myocardial infarction 
 
5.5. 
Concomitant Therapies 
During Visit 1 (Screening), the investigator or designee will question the subject to ensure they 
have not used any excluded therapies.  Concomitant therapies are any new or existing therapies 
used from Screening (Visit 1) until Day 197 (Visit 11).  Concomitant therapies include drug (e.g. 


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prescription and over the counter [OTC]), and non-drug modalities (e.g., chiropractic, physical 
therapy).  
 
5.5.1. 
Permitted Concomitant Therapies 
Subjects will be allowed to use therapies not restricted by the protocol if they have been on a stable 
dose prior to study entry.  Vitamins, minerals, and dietary supplements are permitted while on 
study if the subject has been on a stable dose prior to study entry and, in the opinion of the 
Investigator, will not affect the safety or efficacy of the subject during the study.   
Topical products such as make up and moisturizers used consistently prior to study enrollment on 
the face and eyebrow area should be reviewed by the Investigator and are permitted if, in the 
Investigator’s opinion, they will not affect the assessments of the subject during the study.   
Topical therapies such as topical corticosteroids are permitted if they are not applied on or near 
the eyebrow area. Inhaled or intranasal corticosteroids are allowed in the study. 
 
Prior permitted concomitant medications taken within 30 days of beginning treatment with study 
medication will be documented in the subject’s source document and eCRF.  In addition, any new 
permitted medications administered during protocol treatment and through Day 197 (Visit 11) will 
be documented in the subject’s source document and eCRF.   
 
5.5.2. 
Prohibited therapies 
Any medication or over-the-counter product known to affect hair growth is prohibited throughout 
the study period.  Any prescription topical retinoids, over-the-counter topical products containing 
retinol, alpha hydroxy acids (e.g. glycolic, lactic acids) and beta hydroxy acids (e.g. salicylic acid) 
or cosmetic procedures applied to or in close proximity around the eyebrow area that in the opinion 
of the investigator may affect the safety or efficacy of the subject are prohibited throughout the 
study.  New eyebrow tattooing, microblading, or piercing is not allowed during the study.  During 
this study, subjects are prohibited from using therapies listed in the exclusion criteria. The 
investigator should notify the Medical Monitor, if any prohibited therapies are required to ensure 
subject safety. 
 
5.6. 
Subject Discontinuation from the Study 
Subjects will be informed that they are free to withdraw from the study at any time and for any 
reason.  The Investigator may remove a subject from the study if, in the Investigator’s opinion, it 
is not in the best interest of the subject to continue the study. Examples of other reasons subjects 
may be discontinued from the study are: a change in compliance with an inclusion or exclusion 
criterion, occurrence of AEs, occurrence of pregnancy, or use of a prohibited therapy. Notification 
of discontinuation will immediately (within 24 hours) be made to the Aclaris Therapeutics, Inc. 
study monitor.  
 


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In case of premature discontinuation of study participation, efforts will be made to perform all 
final study day assessments. The date the subject is withdrawn from the study and the reason for 
discontinuation will be recorded in the subject’s source documents and on his/her case report forms 
(eCRFs). All withdrawn subjects with ongoing AEs will be followed as specified in section 8.2.1 
of this protocol. 
 
The study may be discontinued at the discretion of Aclaris Therapeutics, Inc. Some examples of 
reasons for discontinuation are the occurrence of the following: 
 
Increased frequency, severity or duration of known AEs 
 
Medical, business, regulatory or ethical reasons affecting the continued 
performance of the study 
 
Difficulties in the recruitment of subjects 
 
5.7. 
Subject Identifier (SI) 
The investigator or designee will assign a unique five-digit subject identifier (SI) to each subject 
at Visit 1.  
 
The SI format will be NN-NNN where the first 2 digits are the investigational center site number 
(using leading zeroes as appropriate). The final 3 digits are the subject number and must be 
assigned in ascending numerical order, without omitting or repeating any number, starting with 
001. For example, the SI for the second subject that signs an informed consent at site number 01 
would be 01-002.  
 
The subject will be identified using the SI in all study documentation for the duration of the study. 
 
5.8. 
Replacement Subjects 
Subject enrollment will continue until approximately 12 subjects meet all the entry criteria and 
apply study medication at Visit 2 (Baseline). Subjects who are enrolled and do not complete the 
study will not be replaced.  
 
6. 
INVESTIGATIONAL PLAN 
6.1. 
Study Design 
This is an open-label proof of concept study in subjects with unilateral or bilateral loss of some 
or all eyebrow hair due to AA, AU or AT. Subjects will treat affected eyebrow(s) with ATI-
50002 Topical Solution 0.46% twice-daily for 24 weeks and will have a 4-week post-treatment 
follow up visit.  
 
 
 


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6.2. 
Study Flow Chart 
Visit Number 
1 
Screening 
2 
Baseline 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Protocol 
Section 
Week 
-4 to  
-1 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
Day 
-28 to 0 
1 
8 
15
29 57 
85 112
141
169
197 
Informed consent
X
12.3
Subject identifier
X
5.7
Inclusion/exclusion 
criteria
X 
X 
 
 
 
 
 
 
 
 
 
5.3/5.4 
Demographics & 
Medical History 
(including Alopecia 
History)
X 
 
 
 
 
 
 
 
 
 
 
7.3.1 
Brief physical 
examination
X 
 
 
 
 
 
 
 
 
 
X 
7.2.2 
Vital signs (Height 
and Weight at Visit 1 
only)
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
7.2.3 
ECG
X
X
X
X
7.2.1
Clinical laboratory 
sampling
X 
X 
 
 
 
 
X 
 
 
X 
X 
7.2.4 
Serum Pregnancy 
Test for WOCBP
X 
 
 
 
 
 
 
 
 
 
 
7.2.4 
Urine pregnancy test
X
X
X
X
X
X
X
X
7.2.6
Clinician Eyebrow 
Assessment
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
7.1.1 
Subject Eyebrow 
Assessment
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
7.1.2 
Local Tolerability 
Assessment 
(Investigator and 
Subject)
 
X 
Pre & 
Post 
Dose 
X 
X 
X 
X 
X 
X 
X 
X 
X 
7.2.5 
Subject Eyebrow 
Satisfaction
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
7.1.3 
Standardized 
photography 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
7.3.2 
Confirm eligibility
X
6.6.4
Dispense study 
medication
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
6.6.5 
Collect Study 
Medication
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
6.6.5 
Observe first study 
medication 
application
 
X 
 
 
 
 
 
 
 
 
 
6.6.6 
Study medication 
applications
 
 
 
6.6.6 


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Visit Number 
1 
Screening 
2 
Baseline 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Protocol 
Section 
Week 
-4 to  
-1 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
Day 
-28 to 0 
1 
8 
15
29 57 
85 112
141
169
197 
No-treatment follow-
up
 
 
 
 
 
 
 
 
 
 
 
6.6.6 
Subject instructions
X
X
X
X
X
X
X
X
X
X
6.4
Concomitant 
therapies
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
5.5.1 
Adverse events
X
X
X
X
X
X
X
X
X
X
8
 
6.3. 
Study Visits Description and Procedures 
A written, signed informed consent form (ICF) must be obtained from each subject prior to 
performing any study related procedure (i.e., physical examination, clinical laboratory sampling, 
urine pregnancy test, ECG, or photography). 
 
6.3.1. 
Visit 1/ Screening (Week -4 to 0)  
At this visit, the investigator or designee will: 
1. Review and explain the nature of the study to the subject, obtain the subject’s signature on 
the appropriate approved ICF and provide a signed and dated copy to the subject. 
2. Assign a SI to the subject. 
3. Confirm the subject meets all inclusion criteria and no exclusion criteria. 
4. Collect demographic and medical history information (including alopecia history). 
5. Collect concomitant therapies information. 
6. Perform a brief physical examination. 
7. Measure vital signs (including Height & Weight at this visit only). 
8. Conduct an ECG. 
9. Send patient for clinical laboratory tests including serum pregnancy test (if subject is 
WOCBP). 
10. Identify the affected areas of eyebrow(s).  Affected area is defined as the area of the 
eyebrow hair loss identified at baseline. 
11. Perform a Clinician Eyebrow Assessment (CEA); a grade of 0 is required for at least one 
eyebrow with at least 30% eyebrow loss for the subject to continue in the study. Note: the 
subject may have multiple patches of eyebrow hair loss, but at least one distinct patch must 
demonstrate a minimum hair loss of at least 30% (independent of any other patches).  
12. Have the subject complete a Subject Eyebrow Assessment (SEA); a grade of 0 is required 
for at least one eyebrow with at least 30% eyebrow loss for the subject to continue in the 
study. Note: the subject may have multiple patches of eyebrow hair loss, but at least one 
distinct patch must demonstrate a minimum hair loss of at least 30% (independent of any 
other patches). 
13. Review the study instructions with the subject. 
14. Schedule Visit 2 as appropriate. 
 


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6.3.2. 
Visit 2/ Baseline (Day 1)  
This visit must occur within 28 days after Visit 1.  
 
Subsequent study visit dates must be scheduled based on the date of Visit 2. 
 
This visit may not occur before the investigator reviews the Visit 1 clinical laboratory test results 
for all the measured analytes. For the subject to continue in the study all clinical laboratory test 
results must be within the range of normal for the laboratory or, if there are any abnormal results, 
they must be defined as not clinically significant (NCS) by the investigator. For WOCBP, the 
serum pregnancy test from Visit 1 must be negative for a subject to continue in the study. 
 
The investigator must review the evaluator’s interpretation of each subject’s Visit 1 ECG prior to 
Baseline/Visit 2 and comment on the clinical significance of any result that is defined by the 
evaluator as abnormal. The subject must not continue in the study and apply study medication, if 
the Visit 1 ECG meets any of the Criteria in Exclusion Criterion 18). 
 
At this visit, the investigator or designee will perform the following procedures PRIOR TO 
APPLICATION OF STUDY MEDICATION: 
1. Subject should have clinical laboratory tests performed at the local laboratory on the same 
day as the visit. 
2.  Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report changes on the appropriate form. 
3. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form. 
4. Confirm the subject meets all inclusion criteria and no exclusion criteria. 
5. Confirm the subject continues to comply with all study restrictions, is eligible to continue 
in the study and has followed all study instructions. 
6. Measure vital signs. 
7. Perform a urine pregnancy test for WOCBP; results must be negative for the subject to 
apply the first dose of study medication. 
8. The investigator or designee will perform a CEA; a CEA grade of 0 in a distinct patch of 
at least 30% total unilateral eyebrow hair loss is required for the subject to apply the first 
dose of study medication.  Note: the subject may have multiple patches of eyebrow hair 
loss, but at least one distinct patch must demonstrate a minimum hair loss of at least 30% 
(independent of any other patches). 
9. Confirm subject is eligible to apply the first dose of study medication. 
10. Discharge from the study subjects who are not eligible to apply the first dose of study 
medication. 
 
For subjects who are eligible to apply the first dose of study medication the investigator or designee 
will perform the following procedures:  


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1. Have the subject complete a SEA; a SEA grade of 0 in a distinct patch with at least 30% 
total unilateral eyebrow hair loss is required for the subject to apply the first dose of study 
medication.  Note: Subject may have multiple patches of eyebrow hair loss, but at least one 
distinct patch must demonstrate a minimum hair loss of at least 30% (independent of any 
other patches). 
2. Have the subject complete the SES question.  
3. Have the subject perform a pre-application Local Tolerability Assessment (LTA). 
4. The Investigator or designee will perform a pre-application LTA. 
5. Take standardized color photographs. 
6. Conduct an ECG. 
7. Dispense study medication to the subject. 
8. An investigational staff member will instruct the subject on the proper study medication 
application technique and will observe the subject’s first study medication application. 
9. A staff member will monitor the subject for at least 20 minutes after the first study 
medication application completion time to detect any adverse events. 
10. Have the subject perform a post-application LTA 10 (±4) minutes after the application 
completion time.  
11. The investigator or designee will perform a post-application LTA 20 (±4) minutes after the 
application completion time.  
12. Review the study instructions with the subject. 
13. Schedule Visit 3 as appropriate. 
 
6.3.3. 
Visits 3-9 (Weeks 1, 2, 4, 8, 12, 16 and 20)  
These visits must occur on the following weeks after Visit 2: 
 Visit 3, 1 week (±4 days) 
 Visit 4, 2 weeks (±4 days) 
 Visit 5, 4 weeks (±4 days) 
 Visit 6, 8 weeks (±4 days) 
 Visit 7, 12 weeks (±4 days) 
 Visit 8, 16 weeks (±4 days) 
 Visit 9, 20 weeks (±4 days) 
 
At these visits, the investigator or designee will perform the following procedures: 
1. Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report all AEs on the appropriate form. 
2. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form. 
3. Confirm the subject continues to comply with all study restrictions, is eligible to continue 
in the study and has followed all study instructions. 
4. Measure vital signs. 
5. AT VISIT 7 ONLY, send subject for clinical laboratory tests prior to the study visit (on 
the same day). 
6. Have the subject perform a LTA. 
7. The investigator or designee will perform a LTA. 


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8. AT VISITS 5-9 ONLY, the investigator or designee will perform the CEA. 
9. AT VISITS 5-9 ONLY, have the subject complete the SEA. 
10. AT VISITS 5-9, perform a urine pregnancy test for WOCBP; results must be negative for 
the subject to continue in the study. 
11. AT VISIT 7 ONLY, have the subject complete the SES. 
12. AT VISITS 5-9 ONLY, take standardized photographs. 
13. Dispense and/or collect study medication as appropriate. 
14. Review the study instructions with the subject. 
15. Schedule the next visit as appropriate. 
 
6.3.4. 
Visit 10 (Week 24) 
This visit must occur 24 weeks (±4 days) after Visit 2. 
 
At this visit, the investigator or designee will perform the following procedures: 
1. Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report all AEs on the appropriate form. 
2. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form. 
3. Confirm the subject continues to comply with all study restrictions and has followed all 
study instructions. 
4. Measure vital signs. 
5. Conduct an ECG. 
6. Confirm subject had clinical laboratory tests prior to the visit (on the same day).  
7. Perform a urine pregnancy test for WOCBP. 
8. Have the subject perform a LTA. 
9. The investigator or designee will perform a LTA. 
10. The investigator or designee will perform the CEA. 
11. Have the subject complete the SEA. 
12. Have the subject complete the SES.  
13. Collect all study medication. 
14. Take standardized photographs. 
15. Review the study instructions with the subject. 
16. Schedule the next visit as appropriate. 
 
6.3.5. 
Visit 11 (Week 28) 
This visit must occur 28 weeks (±4 days) after Visit 2. 
 
At this visit, the investigator or designee will perform the following procedures: 
1. Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report all AEs on the appropriate form. 
2. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form. 
3. Confirm the subject continues to comply with all study restrictions and has followed all 
study instructions. 


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4. Conduct a brief physical examination. 
5. Measure vital signs. 
6. Conduct an ECG. 
7. Confirm subject had clinical laboratory tests prior to visit (same day). 
8. Perform a urine pregnancy test for WOCBP. 
9. Have the subject perform a LTA. 
10. The investigator or designee will perform a LTA. 
11. The investigator or designee will perform the CEA. 
12. Have the subject complete the SEA. 
13. Have the subject complete the SES.  
14. Take standardized photographs. 
15. Discharge the subject from the study. 
 
6.4. 
Subject Instructions 
An investigational center staff member will dispense and review the Subject Instruction Sheet to 
each subject at Visit 2 through Visit 10 (see Section 14, Appendix A). 
 
6.5. 
STUDY DURATION 
The duration of study participation is anticipated to be a maximum of 233 days per subject. This 
includes the up to 28-day screening period, a 169-day treatment period and a 28 day no-treatment 
follow-up period. The final study visit (Visit 11) has a maximum allowable visit window of +4 
days.   
 
The study end date is the date of the last subject’s last visit.  
 
 


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6.6. 
STUDY MEDICATIONS 
6.6.1. 
Study medication identity 
The study medication for this study is ATI-50002 Topical Solution 0.46%. The study medication 
is a clear, colorless to light pink solution. The inactive ingredients include: water, Transcutol P, 
propylene glycol, PEG400, dimethyl sulfoxide (DMSO), Kolliphor CS 20, benzyl alcohol, 
poloxamer 188, and povidone K30.  The study medications must be stored in a secure area with 
limited access under appropriately controlled and monitored storage conditions. 
 
Study Medication Information 
Study medication name 
ATI-50002 Topical Solution 0.46% 
Manufacturer 
PMRS, Inc., Horsham, PA, USA 
ATI-50002 concentration (%) 
0.46 
Pharmaceutical Form 
Topical Solution 
Container 
Amber Glass Bottles, 30 ml with screw cap 
Storage Conditions 
59°F to 77°F (15°C to 25°C) protected from light, excessive heat, 
open flame and combustibles, out of direct sunlight and in a well-
ventilated, dry area
Dose regimen
Route
Topical
Frequency
Twice-daily application 
Duration of administration
24 weeks 
Other Supplies
Disposable applicators 
 


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6.6.2. 
Study medication packaging and labeling 
The study medication will be packaged in 30 ml amber glass bottles with tamper-resistant caps. 
 
Study medication packaged in individual cartons, each with a unique number, will be provided to 
the investigational center for each subject. An adequate supply of study medication applicators 
will also be supplied. One bottle of study medication is sufficient for approximately 2 weeks of 
twice-daily applications. 
 
Each study medication bottle will be labeled with a one-part label that remains attached to the 
bottle and shows at least the following: 
 Protocol number 
 ATI-50002 Topical Solution 0.46% 
 Storage conditions 
 Sponsor information 
 Investigational drug warning 
 Space to enter Subject Identifier 
 
6.6.3. 
Method of treatment assignment 
This study is an open-label study and all subjects will receive ATI-50002 Topical Solution 0.46%. 
 
6.6.4. 
Subject Eligibility to Receive Study Medication 
At Visit 2 the investigator or designee will determine if the subject is eligible to apply study 
medication. Eligibility requirements include, but are not limited to: 
 The subject must not apply the first dose of study medication unless all the required clinical 
laboratory test results are within the range of normal for the laboratory, or, if there are any 
abnormal results, they must be defined as not clinically significant (NCS) by the 
investigator.  
 For WOCBP, the serum pregnancy test from Visit 1 must be negative for the subject to 
continue in the study.  Additionally, a urine pregnancy test at Visit 2 must be performed 
and found to be negative prior to application of the first dose of study medication. 
 The subject must not apply study medication if the Visit 1 ECG meets any of the Criteria 
in Exclusion Criterion 18). 
 
6.6.5. 
Dispensing and collecting study medication 
The study medications must be dispensed only to study subjects, only at the investigational center 
noted on the FDA Form-1572 and only by authorized personnel as required by applicable 
regulations, guidelines and protocol. 
 
At Visit 2, after a subject is confirmed to be eligible to apply study medication, research center 
staff will assign an initial supply of three study medication bottles.  Research center staff will 
record the SI on each bottle label. 


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At Visits 3-9, examine the subject’s dispensed study medication bottles, collect bottles that are 
empty or do not contain sufficient volume of study medication available for use with the applicator, 
and dispense additional bottles as appropriate following the instructions above. 
 
At Visit 10, collect all dispensed study medication bottles.  
 
Dispense a packet of study medication applicators to the subject each time a study medication 
bottle is dispensed. It is not necessary to collect unused applicators from the subject. 
 
The investigational center staff should make every effort to obtain all dispensed study medication 
from each subject. Two documented telephone contacts with the subject followed by a registered 
letter to the subject constitute adequate follow-up efforts. If these efforts fail, the reason for the 
failure must be noted on the appropriate study medication inventory eCRF and in the subject’s 
source documentation. 
 
6.6.6. 
Study medication application 
The study medications are for external, topical use on the eyebrows on the appropriate study 
subject only.  
 
At Visit 2, the staff member will instruct the subject on the proper application technique as detailed 
in Section 14 and observe the subject’s first study medication application. The staff member should 
record the time that the subject completes the first study medication application. Monitor the 
subject for adverse events for at least 20 minutes after the application completion time. 
 
6.6.7. 
Dose compliance record 
The subject will be given an application calendar to record study medication applications. At every 
post-baseline study visit (Visit 3 and higher), an investigational center staff member will document 
the study medication compliance in the eCRF. 
6.6.8. 
Dose modification 
Subjects should not modify the study medication application procedure or frequency without the 
investigator’s prior approval. All application modifications must be reported on the appropriate 
eCRF.  If any meaningful study medication intolerance or safety issue occurs, after consulting with 
the Aclaris Therapeutics, Inc. Medical Monitor (see page 1), the investigator or designee may 
direct the subject to modify the study medication application frequency. If the subject cannot 
perform the twice-daily application frequency to the affected eyebrow(s) for more than 4 
consecutive days, the subject must be removed from the study. 


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6.7. 
Study Medication Management 
6.7.1. 
Accountability 
The investigator or designee will maintain an accurate record of the receipt of the study medication 
as shipped by Aclaris Therapeutics, Inc. (or designee), including the date received and the 
condition of the study medications. One copy of this receipt will be returned to Aclaris 
Therapeutics, Inc. (or designee) when the contents of the study medication shipment have been 
verified and one copy maintained in the study file. In addition, an accurate study medication 
disposition record will be kept, specifying the amount dispensed for each subject and the date of 
dispensing. This inventory record will be available for inspection at any time. At the completion 
of the study, the original inventory record will be available for review by Aclaris Therapeutics, 
Inc. upon request. 
 
6.7.2. 
Return and disposition of study supplies 
At the completion of the study, all used and unused study medication bottles will be returned to 
Aclaris Therapeutics, Inc. (or designee) for disposal per Aclaris Therapeutics, Inc. (or designee’s) 
written instructions. 
 
6.8. 
Other Study Supplies 
Aclaris Therapeutics, Inc. will provide: 
 Supplies for urine pregnancy tests  
 Equipment, supplies and training for taking standardized photographs 
 Equipment, supplies and training for capturing ECGs for central reading 
 Disposable applicators 
 
6.9. 
Blinding  
6.9.1. 
Verification of blinding 
This study uses an open-label design.  
 
6.9.2. 
Unblinding the study medication 
This is an open-label study. 
 
7. 
STUDY ASSESSMENTS 
The investigator, a designated and appropriately trained staff member (e.g., subinvestigator) or the 
subject will perform the study assessments according to the schedules noted below.  
 
The same individual should perform the assessments for a given subject throughout the study. If 
this becomes impossible, an appropriate designee with overlapping experience with the subject 
and the study should perform the assessments.  


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Similar lighting conditions and subject positioning should be used for all evaluations for a given 
subject. 
 
7.1. 
Effectiveness Evaluations 
The investigator will identify the affected area(s) at baseline in the source document and eCRF.  
The affected area is defined as the area of eyebrow hair loss identified at baseline.   
 
7.1.1. 
Clinician’s Eyebrow Assessment (CEA) 
The CEA is the investigator’s assessment of the affected area of the eyebrow(s) at a particular point 
in time. The investigator should NOT refer to any other assessments to assist with these assessments.  
 
At Visits 1, 2 and 5-11, the investigator or designee will assess the affected area of the eyebrow(s) 
using the scale below and report the one integer that best describes the amount of eyebrow hair 
present.  If both eyebrows are affected, each eyebrow should be evaluated separately: 
 
Clinician’s Eyebrow Assessment 
 
Grade
Descriptor 
0 
No eyebrow hair: No terminal hairs are visible in the affected area(s)  
1 
A little eyebrow hair: Occasional terminal hairs are visible in the affected area(s) 
2 
Some eyebrow hair: Numerous terminal hairs are visible in the affected area(s)  
3 
Most eyebrow hair: Mostly complete eyebrow regrowth with terminal hair in the 
affected area(s) 
4 
Full eyebrow hair: Complete eyebrow regrowth with terminal hair in the affected 
area(s) 
 
At Visit 1 for the subject to be enrolled and at Visit 2 for the subject to continue in the study and to 
apply study medication to one or both eyebrow(s), he or she must have a CEA grade of 0 in a distinct 
patch of at least 30% total hair loss in one or both eyebrows.  Note: the subject may have multiple 
patches of eyebrow hair loss, but at least one distinct patch must demonstrate a minimum hair loss 
of at least 30% (independent of any other patches). 
 
The investigator will record if vellus hair is present (Y/N) in the affected area at Visits 1, 2 and 5-
11. 
 
 


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7.1.2. 
Subject’s Eyebrow Assessment (SEA) 
The SEA is the subject’s assessment of the affected area of the eyebrow(s) at a particular point in 
time. The subject should NOT refer to any other assessments to assist with these assessments.  
 
At Visits 1, 2 and 5-11, the subject will assess the affected area of the eyebrow(s) using the scale 
below and report the one integer that best describes the amount of eyebrow hair present.  If applicable, 
each eyebrow should be evaluated separately: 
 
Subject’s Eyebrow Assessment 
Grade
Descriptor 
0 
No eyebrow hair:  No thick, coarse hairs are visible in the affected area(s) 
1 
A little eyebrow hair: A few thick, coarse hairs are visible in the affected area(s) 
2 
Some eyebrow hair: Numerous thick, coarse hairs are visible in the affected area(s)
3 
Most eyebrow hair: The majority of the affected area(s) of the eyebrow is covered 
in thick, coarse hairs 
4 
Full eyebrow hair:  The affected area(s) of the eyebrow is fully covered in thick, 
coarse hairs 
 
An investigational staff member will identify the eyebrow to be evaluated to the subject, educate the 
subject on the SEA scale before each evaluation and direct the subject to assess the affected area of 
the eyebrow. The staff member should not influence the subject’s assessment. 
 
At Visit 1 for the subject to be enrolled and at Visit 2 for the subject to continue in the study and to 
apply study medication to one or both eyebrows, he or she must have a SEA grade of 0 in at least one 
eyebrow in a distinct patch of at least 30% total hair loss in one or both eyebrows.  Note: the subject 
may have multiple patches of eyebrow hair loss, but at least one distinct patch must demonstrate a 
minimum hair loss of at least 30% (independent of any other patches). 
 
The study staff member will report the SEA grade the subject indicates in the source document for 
each eyebrow. Both the subject and the study staff member must sign/initial the source document 
to indicate the subject performed the SEA as instructed. 
 
 
 


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7.1.3. 
Subject Eyebrow Satisfaction (SES) 
The SES is the subject’s assessment of her/his satisfaction with the status of the affected eyebrow(s), 
relative to the amount of hair present, at a particular point in time. The subject should NOT refer to 
any other assessments to assist with these assessments.  
 
 
At Visits 2, 7, 10 and 11, the subject will assess the affected eyebrow(s) using the scale below and 
report the one integer that best describes her/his satisfaction with the status of the affected eyebrow(s).  
If both eyebrows are affected, each eyebrow should be evaluated separately: 
 
Subject’s Eyebrow Satisfaction 
Grade
Descriptor 
1 
Extremely satisfied
2 
Moderately satisfied
3 
A little satisfied
4 
Neither satisfied or dissatisfied
5 
A little dissatisfied
6 
Moderately dissatisfied
7 
Extremely dissatisfied
 
An investigational staff member will identify the affected eyebrow to be evaluated to the subject, 
educate the subject on the SES scale before each evaluation and direct the subject to assess the 
eyebrow. The staff member should not influence the subject’s assessment. 
 
The study staff member will report the SES grade the subject indicates for each eyebrow in the 
source document. Both the subject and the study staff member must sign/initial the source 
document to indicate the subject performed the SES as instructed. 
 
7.2. 
Safety Evaluations 
The safety in this study will be monitored on a frequent and regular basis and will be formally 
reviewed on a monthly basis by the study investigators, who are experienced in the treatment of 
alopecia, the Sponsor’s medical monitor, and the clinical director.  In addition to reporting adverse 
events throughout the study, the investigator, a designated and appropriately trained staff member 
or the subject, will perform study specific safety assessments according to the schedules noted 
below.   
 
An independent safety monitor will review the safety data monthly or more frequently, if needed. 
 
7.2.1. 
ECGs 
At Visits 1, 2, 10 and 11 a standard 12-lead ECG will be performed by a qualified staff member.  
The ECGs must be obtained using a standard 12-lead ECG with a 10mm/mV amplitude, at 
25mm/sec and a 5-10-second duration. To ensure a steady heart rate the subject must rest quietly 
in the supine position for at least 5 minutes prior to performing the ECG.  


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A central lab will provide equipment, supplies and site training.  In addition, the central lab will 
process the 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 Visit 1 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 significance of any result that is defined by the evaluator as 
abnormal.  
 
Any abnormalities that are, in the opinion of the investigator, CS must be reported as medical 
history if found prior to the start of the first study medication application or as an AE if found after 
the start of the first study medication application. 
 
7.2.2. 
Brief physical examination 
At Visits 1 and 11 the investigator or designee will perform a brief physical examination. The 
examination will include an assessment of the following: 
 General appearance 
 Vital signs (Section 7.2.3) 
 Head, eye, ear, nose and throat (HEENT) 
 Respiratory 
 Cardiovascular 
 Abdominal 
 Extremities 
 Musculoskeletal 
 Lymphatic 
 Skin 
 Neurological 
 
Any measure that is, in the opinion of the investigator, abnormal AND CS must be recorded as 
medical history if found prior to the first study medication application or as an AE if found after 
the first study medication application begins.  
 
7.2.3. 
Vital signs 
At Visits 1-11 a qualified staff member will measure vital signs. The following items will be 
measured: 
 Body temperature 
 Pulse rate 
 Respiration rate 


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 Blood pressure (systolic and diastolic) after the subject sits quietly for at least 5 minutes 
 Height (at Visit 1 only) 
 Weight (at Visit 1 only) 
Any measure that is, in the opinion of the investigator, abnormal AND CS must be recorded as 
medical history if found prior to the first study medication application or as an AE if found after 
the first study medication application begins.  
 
A systolic blood pressure >140mm Hg or a diastolic blood pressure >90mm Hg is considered 
abnormal and therefore must be defined as CS or not clinically significant (NCS) on the eCRFs.  
A weight >300 lbs. is considered abnormal and therefore must be defined as CS or NCS on the 
eCRFs.  
 
7.2.4. 
Clinical laboratory sampling 
Subjects will go to a local laboratory (to be determined) to have the clinical laboratory tests at 
Visits 1, 2, 7, 10 and 11. WOCBP will have urine pregnancy tests performed by the study staff at 
Visit 2, 5, 6, 7, 8, 9, 10 and 11.  Approximately 22.5ml of blood will be collected at Visit 1 and 
10.5ml for each sample at Visits 2, 7, 10 and 11, a total of approximately 64.5ml per subject for 
the entire study. The following tests, at a minimum, will be conducted: 
 
Chemistry Panel 
Complete Blood Count 
Albumin
Hematocrit
Alkaline phosphatase
Hemoglobin
Alanine aminotransferase (ALT)
Platelet count
Aspartate aminotransferase (AST)
Red blood cell morphology
Blood urea nitrogen (BUN)
Red blood cell count
Bicarbonate
White blood cell count
Calcium
White blood cell differential
Chloride
   % & absolute
Creatinine
   Basophils
Glucose
   Eosinophils
Lactate dehydrogenase (LDH)
   Lymphocytes
Phosphorus
   Monocytes
Potassium
   Neutrophils
Sodium
Total bilirubin
Complete Urinalysis
Total protein
Uric acid 
Total cholesterol, LDL, HDL 
Triglycerides 
 
Screening Tests Only 
Virology (HepB, HCV, HIV) 
Total Iron Binding Capacity (TIBC) 
Serum Iron
 


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Serum Ferritin 
T3/T4, TSH 
Quantiferon  
Serum Pregnancy (Visit 1 only) 
The results of the clinical laboratory tests will be reported on the laboratory’s standard reports. 
The investigator must review all laboratory reports in a timely manner and note NCS or CS to 
define the clinical significance of any result that is outside the normal range for the laboratory. The 
investigator must date and initial every laboratory report.  
 
The investigator must review the Visit 1 laboratory results for all the required analytes for each 
subject prior to Visit 2. The subject must not continue in the study and apply study medication if 
at Visit 2 any of the Visit 1 results are outside normal range for the laboratory AND, in the opinion 
of the investigator, CS. 
 
The investigator must report all laboratory results that are BOTH outside the normal range for the 
laboratory AND, in the opinion of the investigator, CS as medical history if found prior to the first 
study medication application or as an AE if found after the first study medication application 
begins.  
 
7.2.5. 
Local Tolerability Assessment (LTA) 
The LTA is the investigator’s assessment of the average overall severity of signs and the subject’s 
assessment of the average overall severity of symptoms associated with irritation on each eyebrow 
considered separately. The investigator and subject must NOT refer to any other evaluation to assist 
with these assessments. This is not a comparison with the assessment at any other time point. 
 
At Visits 2-11, the investigator and the subject will evaluate the LTA signs and the LTA symptoms 
respectively.  
 
LTA Signs (assessed by the investigator for each eyebrow separately): 
 Erythema 
 Edema 
 Scaling/dryness 
 
LTA symptoms (assessed by the subject for each eyebrow separately): 
 Stinging 
 Burning 
 
The investigator will assess the LTA signs as follows: 
 At Visit 2: 
o Prior to the first study medication application 
o 20 (±4) minutes after the application completion time. 
 At Visits 3-11 
 


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The subject will assess the LTA symptoms as follows: 
 At Visit 2: 
o Prior to the first study medication application report the LTA for each symptom 
over the previous 24 hours 
o 10 (±4) minutes after the application completion time report the average severity 
since the application completion time 
 At Visits 3-11: 
o Report the average LTA for each symptom over the previous 24 hours 
 
The investigator, for the signs, should report the one integer that best describes the average overall 
severity on each eyebrow separately using the scales below: 
 
Local Tolerability Assessment – Erythema 
Grade
Descriptor
0
Clear: No erythema present
1
Mild: Slight erythema
2
Moderate: Definite erythema
3
Severe: Marked, fiery erythema
 
Local Tolerability Assessment – Edema 
Grade
Descriptor
0
Clear: No edema present
1
Mild: Slight edema
2
Moderate: Definite edema
3
Severe: Marked edema
 
Local Tolerability Assessment – Dryness/Scaling 
Grade
Descriptor
0
Clear: No signs of dryness or scaling
1
Mild: Slight roughness (may be more easily felt than seen), barely perceptible scaling
2
Moderate: Moderate roughness, definite scaling
3
Severe: Marked roughness, heavy scaling
 
The subject, for the symptoms, should report the one integer that best describes the average overall 
severity on each eyebrow separately using the scales below: 
 
Local Tolerability Assessment – Stinging 
Grade
Descriptor
0
Clear: No stinging
1
Mild: Slight tingling, not bothersome
2
Moderate: Definite tingling, slightly bothersome
3
Severe: Intense stinging, bothersome and/or uncomfortable
 
 
 


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Local Tolerability Assessment – Burning 
Grade
Descriptor
0
Clear: No burning
1
Mild: Slight warmth, not bothersome
2
Moderate: Definite warmth, slightly bothersome
3
Severe: Intense feeling of heat, bothersome and/or uncomfortable
 
Follow these steps to complete the LTA for each symptom by a subject: 
 An investigational center staff member, other than the evaluating investigator, will show 
the appropriate LTA symptom grading scale to the subject and instruct the subject on the 
time interval to be considered. 
 The staff member should not give any opinion on the meaning of the LTA descriptors. 
 The subject should verbally indicate the appropriate grade for each eyebrow for each 
symptom and the staff member will report the grade in the source document. 
 Both the subject and the staff member must sign/initial the source document to indicate the 
subject performed the LTA for symptoms as instructed. 
 The staff member must not influence the subject’s assessment. 
 
7.2.6. 
Urine Pregnancy tests 
At Visits 2, and 5-11, a qualified staff member will perform a urine pregnancy test for subjects 
who are WOCBP. The urine pregnancy test kits used must have a minimum sensitivity of 25-mIU 
ß-HCG/milliliter (ml) of urine.  
 
Subjects who are WOCBP must have a negative serum pregnancy test result at Visit 1 to continue 
in the study and a negative urine pregnancy test at Visit 2 to be continue in the study and apply 
study medication.    
 
If the result of any urine pregnancy test is positive following initial study medication application, 
the subject will be withdrawn from the study and the subject’s pregnancy documented and 
followed. 
 
7.3. 
Other Evaluations 
7.3.1. 
Demographics, medical history and alopecia areata history 
During 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 ethnicity.  
 


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The investigator or designee will interview each subject to obtain medical history information 
related to all medical conditions and disease states that, at Visit 1: are ongoing, require concomitant 
therapy or are, in the opinion of the investigator, relevant to the subject’s study participation.  The 
investigator or designee will also obtain an AA, AU or AT history at Visit 1.  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, bilateral tubal ligation, or hysterectomy.   
 
7.3.2. 
Standardized photography 
At Visits 2 and 5-11 a qualified investigational center staff member will take standardized color 
photographs of each subject’s eyebrows.  
 
The photographs are to document the status of each subject’s eyebrows. The subject’s identity will 
not be revealed in the study photographs. 
 
At Visit 2, the photographs must be taken prior to the first study medication application. 
 
Equipment, supplies, training and detailed instructions for obtaining and managing the 
photographs will be provided to the investigational center prior to the initiation of subject 
enrollment. 
  
8. 
ADVERSE EVENTS 
Adverse events will be monitored throughout the study and immediately reported on the 
appropriate Aclaris Therapeutics, Inc. AE eCRF.   
 
8.1. 
Definitions 
8.1.1. 
Adverse events (AE) 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a study medication and which does not necessarily have a causal relationship with 
the study medication. An AE can therefore be any unfavorable and unintended sign or symptom 
associated with the use of a study medication (including an abnormal laboratory finding), whether 
or not related to the study medication. Thus, any new, or clinically significant worsening of an 
existing sign, symptom or disease, should be considered an AE.  
 
Worsening of any of the eyebrow assessments should be reported as an AE ONLY if the use 
of the study medication is interrupted or discontinued or if therapy is required to manage 
the event.  
 
The investigator must, for any AE in a study medication treatment area, question the subject 
in detail to determine if there are any confounding factors (e.g., irritation by cosmetics) for 
any such AE.  
 


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Every new episode or clinically significant worsening of a chronic condition (e.g., headaches, 
seasonal allergies, depression, and hypertension) should be reported as a separate AE, even if the 
condition is reported in the subject’s medical history. 
 
The investigator should, when certain, report a diagnosis rather than the signs, symptoms or 
clinically 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 application should be reported 
as medical history, not as an AE. 
 
8.1.2. 
Serious adverse event (SAE) 
A Serious Adverse Event is any untoward medical occurrence that at any dose: 
 Results in death 
 Is life threatening 
 Requires inpatient hospitalization or prolongation of existing hospitalization 
 Results in persistent or significant disability/incapacity, or 
 Is a congenital anomaly/birth defect 
 Is an important medical event 
 
The term “life threatening” refers to an event in which the subject was at risk of death at the time 
of event; it does not refer to an event that hypothetically might have caused death if it was more 
severe. 
 
Inpatient hospitalization is considered to have occurred if the subject is admitted to the hospital on 
an in-patient basis, even if released the same day. Prolongation of hospitalization is defined as an 
additional night stay in the hospital. Hospitalization for a diagnostic test (even if related to an AE) 
or elective hospitalization that was planned before study enrollment (signing the ICF) are not 
themselves reasons for an event to be defined as a SAE. 
 
Important medical events are those that may not be immediately life threatening, result in death or 
hospitalization, but are clearly of major clinical significance and may jeopardize the subject or 
require intervention to prevent one of the outcomes listed in the SAE definition above. These 
should also usually be considered serious. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasia or convulsions that do not 
result in hospitalization. 
 
8.1.3. 
Adverse event reporting period 
The investigator must start reporting non-serious AEs and SAEs starting with the subject’s first 
study medication application continuing until the end of the subject’s last study visit. 
 


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8.1.4. 
Severity 
The investigator must define the severity of each AE using the following definitions as a guideline. 
The investigator will consider the range of the possible severity of the event and identify the 
severity that is the most appropriate according to her/his medical judgment. 
 
Mild – Awareness of signs or symptom, but easily tolerated. 
Moderate – Discomfort, enough to cause interference with usual activity. 
Severe – Incapacitating with inability to perform usual activity. 
8.1.5. 
Relationship to study medication 
The investigator will determine if there is a reasonable causal relationship between the study 
medication and an AE or not. The investigator will use her/his best medical judgment and consider 
all relevant factors (e.g., temporal relationship, location of the event, the subject’s relevant medical 
history, concomitant therapies and concurrent conditions) to determine the relationship of the AE 
to the study medication. The investigator will define the relationship of an AE to the study 
medication by selecting one of the following categories: 
 
Related – There is a reasonable possibility that there is a causal relationship between the 
study medication and the AE. 
 
Not Related – There is not a reasonable possibility that there is a causal relationship 
between the study medication and the AE. 
 
The term “reasonable causal relationship” means there are facts or arguments to suggest a causal 
relationship (International Conference on Harmonization (ICH) E2A). 
 
8.2. 
Reporting Procedures 
8.2.1. 
Procedures for reporting adverse events 
At each post randomization visit (Visit 2), the investigator or designee will question the subject to 
elicit AEs using a non-directive question such as “Has there been any change in your health since 
the previous study visit?”   
 
At Visit 2, the investigator or designee will monitor the subject for at least 20 minutes after the 
first study medication application at Visit 2 to elicit AEs in a similar manner. 
 
If appropriate, based on the subject’s response to non-directed questioning regarding AEs, the 
investigator or designee will follow-up with directed questions and appropriate evaluations.  
Any AE noted during the reporting period must be reported in the source documents and on the 
appropriate AE eCRF.  
 


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AEs that are defined as “Not Related” to the study medications will be followed until they are 
resolved or until the subject’s last study visit. AEs that are defined as “Related” to the study 
medications will be followed until they are resolved or, if not resolved after the subject’s last study 
visit, until in the opinion of the investigator, the AE reaches a clinically stable outcome with or 
without sequelae. 
 
8.2.2. 
Procedure for reporting a serious adverse event 
Upon becoming aware of a SAE occurring during the AE reporting period, whether or not related 
to the study medication, 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 
 Fax: (866)-681-1063 
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 (Aclaris Therapeutics, Inc. Safety 
Monitor). 
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 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). 
 
8.2.3. 
Safety Monitoring ECG Discontinuation Criteria 
Any subject who develops any of the following ECG criteria during the active treatment phase will 
be instructed to stop study medication and will be withdrawn from the study: 
 A post-study medication ECG result where the evaluator’s interpretation shows any of the 
following: 
 Clinically significant rhythm disturbance other than sinus rhythm or ectopic 
supraventricular rhythm (ectopic atrial rhythm) 
 Clinically significant conduction disturbance including PR >240msec, pre-
excitation (delta wave and PR <120msec), second degree or higher AV block  


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 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) 
 Evidence of QT-interval prolongation, defined as an increase in the QTcF interval 
>60ms from Visit 1 
 New QTcF > 500 ms 
 Acute signs of ischemia or infarction 
 Any ECG abnormality which may, in the opinion of the investigator, represent a 
new medical issue of concern 
 
8.2.4. 
Study Medication Interruption and Discontinuation 
8.2.4.1 
Study Medication Interruption 
Treatment with ATI-50002 Topical Solution should be temporarily interrupted in the event of 
severe adverse events considered related to ATI-50002, or in the event of one or more of the 
abnormal laboratory values in Table 1. 
 
Table 1:  Study Medication Interruption Criteria 
Laboratory Test 
Interrupt 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 
Hemoglobin 
< 8 g/dL or decrease > 2 g/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 1, the investigator 
or designee upon receipt and review of the central laboratory report should instruct the subject to 
interrupt 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 1.  
If the retest confirms the abnormal laboratory value, then the study medication interruption should 
continue, 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) return to normal or to baseline 
values.  Application of study medication may be resumed upon resolution of the abnormal 
laboratory values to the levels specified in Table 1 above.  


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8.2.4.2 
Study Medication Discontinuation 
Study medication should be permanently discontinued in the event of any of the following: 
 Severe infection requiring parenteral antimicrobial therapy or hospitalization 
 Symptomatic herpes zoster 
 Malignancy – except for non-melanoma skin cancer (e.g., squamous or basal cell 
carcinoma) 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: 
 > 5 x ULN persisting for 1 week of study medication interruption or second event 
of > 5 x ULN 
 > 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%)]. 
 Serum creatinine: > 2 x ULN persisting for >2 weeks of treatment discontinuation or 
second occurrence of > 2 x ULN 
The continued treatment of subjects who experience other serious or severe adverse events 
considered related to study treatment should be discussed with the Sponsor’s medical monitor. 
 
9. 
PREGNANCY 
9.1. 
Definition of Women 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 (Visit 1) and a negative UPT at Baseline (Visit 2) prior to randomization and monthly 
throughout the study. 
 
9.2. 
Highly Effective Methods of Birth Control 
The Investigator or subinvestigator 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- 


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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 application 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 (study duration and 30 days after 
the last study medication application). The reliability of sexual 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 ≥90 days) 
 Injectables (on a stable dose for ≥90 days) 
 Patches (on a stable dose for ≥90 days) 
 Combined oral contraceptives (on a stable dose for ≥90 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 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.  


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If, following study medication administration, it is determined that the subject may have been or 
was pregnant at the time of study medication exposure (including at least 2 days after study 
medication administration) the investigator must immediately notify the Aclaris Therapeutics, Inc. 
Medical Monitor and record the event on a pregnancy surveillance form. While not an AE or SAE, 
the investigator must report every pregnancy using a pregnancy surveillance form and follow the 
reporting procedures described for SAE reporting as described in Section 8.2.2. 
 
Protocol-required procedures for trial discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy (e.g., x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated. In addition, the investigator must report 
to 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.  
 
If the outcome of the pregnancy meets the criteria for an SAE (i.e., ectopic pregnancy, spontaneous 
abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a live born, a 
terminated fetus, an intrauterine fetal demise, or a neonatal death]), the investigator should follow 
the procedures for reporting SAEs. 
 
10. 
STATISTICAL ANALYSES 
10.1. 
Statistical Methods 
Summary descriptive statistics (N, mean, median, SD) by visit will be provided for all safety and 
efficacy parameters.  Primary and secondary efficacy parameters are described below: 
 
Mean change from baseline in eyebrow growth will be calculated as the mean change in the 
Clinician’s Eyebrow Assessment (CEA) from Visit 2 (Baseline) compared to end of treatment 
(Visit 10). The CEA evaluates eyebrows on a scale from “No eyebrow hair” (grade 0) to “Full 
eyebrow hair” (grade 4).     
 
Mean change from baseline in the Subject’s Eyebrow Assessment (SEA) will be calculated from 
Visit 2 (Baseline) to end of treatment (Visit 10). 
 
Mean change from baseline in the Subject’s Eyebrow Satisfaction (SES) will be calculated from 
Visit 2 (Baseline) to end of treatment (Visit 10). 
 
All efficacy summaries will be based on the per-protocol population including all subjects who 
have Baseline (Visit 2) and Visit 10 efficacy data and no major protocol violations. 
 
Safety analyses will include descriptive statistics calculated on the safety parameters using the 
safety population. The proportion of subjects with treatment-emergent adverse events will be 
tabulated and presented by Medical Dictionary for Regulatory Activities (MedDRA) System 
Organ Class. Vital signs and clinically significant abnormal laboratory results will also be 


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tabulated and presented. Change from baseline in the Local Tolerability Assessments (LTA) to 
end of treatment (Visit 10) will be summarized.  
 
Data from all enrolled and treated subjects will be presented and summarized. Safety summaries 
will include listings by study medication of adverse events incidences within each MedDRA 
System Organ Class, and changes from pre-application values in vital signs. Adverse event 
summaries will be presented by study medication showing the proportion of subjects 
experiencing adverse events, both overall and by MedDRA System Organ Class.   
 
10.2. 
Sample Size 
This is the first US-based study with topical ATI-50002 Topical Solution for the treatment of 
eyebrow loss due to AA, AU/AT.  No formal power calculations will be performed.  
 
11. 
TRAINING, MONITORING, DATA MANAGEMENT AND QUALITY 
ASSURANCE 
11.1. 
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. 
 
11.2. 
Monitoring 
The conduct of the study will be closely monitored by representatives of Aclaris Therapeutics, Inc. 
to verify adherence to ICH Good Clinical Practice (GCP) guidelines and applicable SOPs.  Reports 
of these verifications will be archived with the study report.  The investigator will allow the Aclaris 
Therapeutics, Inc. representatives designee and/or and any regulatory agency to have direct access 
to all study records, eCRFs, corresponding subject medical records, study medication dispensing 
records and study medication storage area, and any other documents considered source 
documentation.  The investigator also agrees to assist the representative, if required. 
 


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11.3. 
Data Management 
Data management activities of this study will be subcontracted.  Edit checks and review processes 
will be performed by the sub-contractor until all data clarifications are resolved. The data will be 
exported to be stored in SAS datasets (or equivalent) by the sub-contractor. After all data 
clarifications are resolved and subject’s evaluability is determined, the database will be locked. 
 
11.4. 
Quality Assurance 
The study is conducted under the sponsorship of Aclaris Therapeutics, Inc. in compliance with the 
applicable regulatory requirements as well as applicable ICH guidelines, 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.  
 
12. 
ETHICS AND GENERAL STUDY CONDUCT CONSIDERATIONS 
12.1. 
Institutional Review Board (IRB)/Ethics Committee (EC) 
This protocol, informed consent form, any information provided to subjects, subject-recruiting 
advertisements, and any amendments to these items will receive IRB/EC approval prior to use. 
 
The IRB/EC must receive a copy of the Investigator’s Brochure, all protocol amendments, safety 
reports and other study related information as required by regulation or the IRB/EC procedures. 
 
12.2. 
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 sites, in compliance with HIPAA. The study will be conducted in compliance with 
the IRB/EC approved version of the protocol and any applicable amendments. 
 
This protocol, informed consent form, any information provided to subjects, subject-recruiting 
advertisements, and any amendments to these items will receive IRB/EC approval prior to use. 
Subjects will provide voluntary informed consent prior to initiation of any study related 
procedures. 
 


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12.3. 
Subject Information and Consent 
All subjects who participate in this study must be fully informed about the study in accordance 
with the GCPs, federal regulations, local regulations and, at US investigational sites, with HIPAA.  
The ICF will contain all the required elements in compliance with the current ICH E6 GCP 
guideline, local regulatory requirements. The investigator must have a defined process for 
obtaining voluntary informed consent from every subject.  
 
The ICF, approved by an IRB/EC, will be fully explained to the subject.  Prior to any study related 
procedures, including washout from therapies, the subject will voluntarily sign and date the ICF. 
The investigator must maintain each subject’s ICF in the investigational center’s study file and 
must provide each subject with a copy of the signed and dated ICF. 
 
12.4. 
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 Aclaris 
Therapeutics, Inc. and prior review and documented approval from the IRB/EC. 
 
Changes that involve only logistical or administrative changes are allowed.  The investigator 
should document and explain any deviation from the protocol.  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. 
 
12.5. 
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. 
 
12.6. 
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. 
 


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12.7. 
Data Collection and Archiving 
12.7.1. 
Data collection  
The Investigator must maintain required records for all study subjects.  Data for this study will be 
recorded in the subject's source document and on the 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. 
 
12.7.2. 
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.   
 
12.7.3. 
Archiving 
All pertinent data, samples, photographs, correspondence, original or amended protocol, reports 
and all other material relating to the study will be maintained securely in Aclaris Therapeutics, Inc. 
/contract research organization/investigator archives for the legally required duration for archiving. 
 
The investigator should maintain the essential study documents as specified in ICH GCP, and in 
compliance with all regulatory requirements. The investigator should ensure these documents are 
protected from accidental destruction or disposal. 
 
If the Investigator needs to re-assign responsibility for maintaining these documents (e.g., due to 
retirement) it must be transferred to a person willing to accept this responsibility.  The investigator 
must notify Aclaris Therapeutics, Inc., in writing, of the name and address of the new individual. 
 
 
 
 


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13. 
References 
Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: Part II. 
Treatment. J Am Acad Dermatol. 2010;62(2):191-202. 
Arca E, Muşabak U, Akar A, Erbil AH, Taştan HB. Interferon-gamma in alopecia 
areata. Eur J Dermatol. 2004 Jan-Feb;14(1):33-6.  
ATI-50002 Topical Solution Investigator’s Brochure, August 2017. 
Barahmani N, Schabath MB, Duvic M; National Alopecia Areata Registry. History  
of atopy or autoimmunity increases risk of alopecia areata. J Am Acad Dermatol. 
2009 Oct;61(4):581-91.  
Bilgiç Ö, Bilgiç A, Bahalı K, Bahali AG, Gürkan A, Yılmaz S. Psychiatric symptomatology and 
health-related quality of life in children and adolescents with alopecia areata. J Eu Acad 
Dermatol Venereol. 2014;28(11):1463-1468. 
Christiano, A.  2016.  Data on File.  
Craiglow BG, King BA. Killing Two Birds with One Stone: Oral Tofacitinib Reverses Alopecia 
Universalis in a Patient with Plaque Psoriasis. J Invest Dermatol. 2014;134(12):2988-2990. 
Craiglow BG, Liu LY, and King BA. Tofacitinib for the treatment of alopecia areata and variants in 
adolescents. J Am Acad Dermatol. 2017;76(1):29-32.  
Delamere FM, Sladden MJ, Dobbins HM, Leonardi-Bee J. Interventions for alopecia areata. 
Cochrane Database Syst Rev. 2008;16(2). 
Gilhar A, Kam Y, Assy B, Kalish RS. Alopecia areata induced in C3H/HeJ mice by 
interferon-gamma: evidence for loss of immune privilege. J Invest Dermatol. 2005;124(1):288-9.  
Gupta AK. Efficacy of tofacitinib in treatment of alopecia universalis in two patients. J Eur Acad 
Dermatol Venereol. 2016;30(8):1373-1378. 
Hirota R, Tajima S, Yoneda Y, Okada M, Tashiro J, Ueda K, Kubota T, Yoshida R. 
Induction of hair regrowth in the alopecia site of IFN-gamma knockout mice by 
allografting and IFN-gamma injection into the transplantation site. J Interferon  
Cytokine Res. 2003 Aug;23(8):433-9. 
Hordinsky MK. Current Treatments for Alopecia Areata. J Investig Dermatol Symp Proc. 
2015;17(2):44-46. 
Jabbari A, Dai Z, Xing L, et al. Reversal of Alopecia Areata Following Treatment With the JAK1/2 
Inhibitor Baricitinib. EBioMedicine. 2015;2(4):351-355. 
Jabbari A, Cerise JE, Chen JC, Mackay-Wiggan J, Duvic M, Price V, Hordinsky M, Norris D, 
Clynes R, Christiano AM. Molecular signatures define alopecia areata 
subtypes and transcriptional biomarkers. EBioMedicine. 2016 May;7:240-7. 
Kim BY and Kim HS. Successful hair growth in a Korean patient with alopecia universalis 
following tofacitinib treatment. Singapore Med. J., 2017 May; 58(5): 279-280. 
Kuwano Y, Fujimoto M, Watanabe R, Ishiura N, Nakashima H, Ohno Y, Yano S, 
Yazawa N, Okochi H, Tamaki K. Serum chemokine profiles in patients with alopecia  
areata. Br J Dermatol. 2007:157(3):466-73.  
Pieri L, Guglielmelli P, Vannucchi AM. Ruxolitinib-induced reversal of alopecia universalis in a 
patient with essential thrombocythemia. Am J Hematol. 2015;90(1):82-83. 
Price VH. Treatment of Hair Loss. N Eng J Med. 1999;341(13):964-973. 
Price VH, Hordinsky MK, Olsen EA, et al. Subcutaneous efalizumab is not effective in the 
treatment of alopecia areata. J Am Acad Dermatol. 2008;58(3):395-402. 


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Ruiz-Doblado S, Carrizosa A, García-Hernández MJ. Alopecia areata: psychiatric comorbidity and 
adjustment to illness. Int J Dermatol. 2003;42(6):434-437. 
Safavi KH, Muller SA, Suman VJ, Moshell AN, Melton Iii LJ. Incidence of Alopecia Areata in 
Olmsted County, Minnesota, 1975 Through 1989. Mayo Clinic Proc. 1995;70(7):628-633. 
Scheinberg M, and Ferreira SB. Reversal of Alopecia Universalis by Tofacinitinib: A Case Report; 
Ann Intern Med.; 2016 Nov 15; 165(10): 750-751. doi: 10.7326/L16-0125. 
Strober BE, Siu K, Alexis AF, et al. Etanercept does not effectively treat moderate to severe 
alopecia areata: An open-label study. J Am Acad of Dermatol. 2005;52(6):1082-1084. 
Tosti A, Bellavista S, Iorizzo M. Alopecia areata: a long term follow-up study of 191 patients. J Am 
Acad Dermatol. 2006;55(3):438-441. 
Weise K, Kretzschmar L, John SM, Hamm H. Topical Immunotherapy in Alopecia areata: 
Anamnestic and Clinical Criteria of Prognostic Significance. Dermatology. 1996;192(2):129-
133. 
Whiting, D.A., 2003. Histopathologic features of alopecia areata: a new look. Arch. 
Dermatol. 139, 1555–1559.  
Xing L, Dai Z, Jabbari A, et al. Alopecia areata is driven by cytotoxic T lymphocytes and is 
reversed by JAK inhibition. Nat Med. 2014;20(9):1043-1049. 
 
 
 
 
 


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14. 
APPENDIX A:  PARTICIPANT INSTRUCTION SHEET 
General Instructions: 
1. Before application of study medication, your face and eyebrow area should be clean (free 
of any makeup, moisturizers, sunscreen, etc.), and dry. This will allow the study 
medication to penetrate down into the skin to ensure you are getting the best application. 
2. The study doctor will instruct you to apply study medication to one or both eyebrows. 
You will apply the study medication to the entire eyebrow area, both with and without 
eyebrow hair.   
3. You will be asked to apply a thin layer of study medication to the affected eyebrow with 
an applicator as instructed by the study doctor or the study staff. Keep applying study 
medication to the affected eyebrow(s) throughout the study, even if hair is re-growing in 
these areas. 
4. You will want the tip of your applicator to be saturated but not too much as to cause 
dripping.  An applicator should only be dipped in the bottle once and then disposed of. 
5. Keep the study medication out of your eyes.  If the study medication gets in your eyes, 
rinse the area well with water for up to 15 minutes.  Contact the study doctor for further 
advice on managing the eye exposure. 
6. You will apply study medication twice-a-day, approximately 8 to 12 hours apart.  Once 
you apply study medication, do not wash your face and eyebrow area or participate in 
strenuous exercise that would cause profuse sweating for at least 6 hours. 
7. Remember to bring your study medication bottles, both used and unused, to each study 
visit. 
8. Avoid exposing your face to excessive natural or artificial ultraviolet radiation (e.g., 
sunlight, tanning beds) and use sunscreen on the face including the eyebrows, if 
excessive sun exposure cannot be avoided. 
9. Remove any products applied to the eyebrow area at least 1 hour before study visits.  Do 
not apply study medication less than 6 hours before a study visit. If your visit is in the 
morning you should wait until after the visit to apply your study medication. 
10. Each bottle of study medication should be used for 14 days only, even if there is 
remaining study medication.  
 
Preparation for Study Medication Application 
1. Gather a clean, dry washcloth or towel, the study medication bottle, disposable 
applicators and a mirror. 
2. Wash your hands with soap and water before and after using this study medication. 
3. Gently wash your face, ensuring your eyebrow areas are clean. Use your normal 
cleansing regime as approved by your study doctor.  Do not use abrasive cleansers or 
materials on your face and eyebrow area.  
4. Pat your face dry with a clean towel and then let it air dry until it is completely dry to the 
touch. 
 
 
 


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Study Medication Application: 
1. Unscrew the cap from the bottle.  Place the open bottle on a stable, level surface.   
2. Dip a disposable applicator into the bottle of study medication for about 2 seconds. Tap 
the tip of the applicator twice inside the edge of the bottle to remove any excess study 
medication.  The applicator should be saturated, but not dripping.   
3. Tilt your head back and place your clean, dry washcloth over one eye. Swipe the 
applicator across your affected eyebrow ridge above the covered eye, applying a thin 
layer of study medication over the entire affected eyebrow area.  Your eyebrow area 
should be wet, but not dripping wet.  Dispose of the applicator.  Do not dip the same 
applicator in the study medication bottle more than once. 
4. If you need additional study medication to cover your entire affected eyebrow, use a new 
applicator and repeat the application process as described in #2 and #3.  
5. If you are instructed by the study doctor to treat both eyebrows, apply study medication 
to your other eyebrow following instructions in #2, #3, and #4. 
 
After Study Medication Application 
1. Securely close the study medication bottle and dispose of any used applicators.   
2. Wash your hands after using this product. 
3. Allow the study medication to completely dry for at least 10 minutes. 
4. Do not apply any products (moisturizers, sunscreens, cosmetics, etc.) to your eyebrow 
area until the study medication has completely dried, at least 30 minutes after applying 
study medication. 
5. Do not wash your face and eyebrow areas or participate in strenuous exercise that would 
cause profuse sweating for at least 6 hours after applying the study medication. 
 
Missed Doses 
If you miss a dose of this study medication, 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.  Tell 
the study staff about any missed doses at your next study visit. 
 
Storage 
Store the study medication in the original glass bottle at room temperature, away from heat, 
moisture, and direct light. Do not refrigerate or freeze. Keep out of reach of children.