Clinical trial NCT03354637
Conditions: Alopecia Areata
Sponsor: Aclaris Therapeutics, Inc.
Start date: 2017-11-29; Completion date: 2019-09-10
Enrollment: 129 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Primary:

• To assess safety, tolerability and efficacy of 2 dose strengths of ATI-50002 Topical Solution, compared to vehicle in subjects with alopecia areata (AA)

Secondary:

• To evaluate key clinical outcome assessments

Detailed description:
Primary:

• To assess safety, tolerability and efficacy of 2 dose strengths of ATI-50002 Topical Solution, compared to vehicle in subjects with alopecia areata (AA)

Secondary:

• To evaluate key clinical outcome assessments

Arms: arm 1: High dose active arm 2: low dose active arm 3: placebo
Interventions: intervention 1: ATI-50002 high dose intervention 2: ATI-50002 low dose intervention 3: Placebo
Intervention descriptions: intervention 1: Topical solution intervention 2: Topical solution intervention 3: Topical solution

Protocol documents:
Prot_001.pdf: 
Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 1 of 82 
Version 9.0, Date: 09APR2019 
   CLINICAL STUDY PROTOCOL 
Protocol Number: ATI-50002-AA-201 
Amendment 8 
 
A Randomized, Double-Blind, Vehicle-Controlled Multicenter Study to Evaluate the 
Safety, Tolerability and Efficacy of ATI-50002 Topical Solution Administered Twice-Daily 
for 6 Months in Adolescents and Adult Subjects with Stable Patchy Alopecia Areata with 
Optional Long-Term Open-Label Extension 
 
Sponsor 
Aclaris Therapeutics, Inc. 
640 Lee Rd 
Suite 200 
Wayne, PA 19087 
Telephone: 484-324-7933 
Facsimile: 484-320-2344 
 
Study Contact 
Sue Moran, RN, MSN 
Sr. Director, Clinical Development 
Aclaris Therapeutics, Inc. 
640 Lee Rd 
Suite 200 
Wayne, PA 19087 
Telephone: 484-329-2129 
Cell: 484-999-7492 
E-mail: smoran@aclaristx.com 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical Monitor 
Evyan Cord-Cruz, M.D. 
Director, Medical Affairs 
Symbio, LLC 
21 Perry Street 
Port Jefferson, NY 11777 
Telephone (Main Line): 631-403-5126 
Telephone (Office): 516-338-0647 
Telephone (Cell): 516-982-0677 
Facsimile:  631-474-8534 
E-mail: ecruz@symbioresearch.com 
 
Safety Monitor: 
Deborah S. Kelly, M.D. 
Senior Medical Director, Safety, PV & Risk 
Management 
Aclaris Therapeutics, Inc. 
640 Lee Rd 
Suite 200 
Wayne, PA 19087 
Telephone: 484-540-2262 
Cell: 484-280-2262 
Email: dkelly@aclaristx.com 
ProPharma 
Email:  clinicalsafety@propharmagroup.com 
 
 
 
 
 
 
 
 
This document is a privileged and confidential communication of Aclaris Therapeutics, Inc. Acceptance of this 
document constitutes an agreement by the recipient that no unpublished information contained herein will be used, 
published or disclosed without prior written approval from Aclaris Therapeutics, Inc. 




Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 3 of 82 
Version 9.0, Date: 09APR2019 
INVESTIGATOR SIGNATURE PAGE 
Protocol Number:  ATI-50002-AA-201 Amendment 8 
 
Protocol Title:  A Randomized, Double-Blind, Vehicle-Controlled Multicenter Study to Evaluate the 
Safety, Tolerability and Efficacy of ATI-50002 Topical Solution Administered Twice-Daily for 6 Months 
in Adolescents and Adult Subjects with Stable Patchy Alopecia Areata with Optional Long-Term Open-
Label Extension 
Version 9.0:  09APR2019    
 
I have reviewed the above-titled protocol and agree that it contains all the information necessary to conduct 
the study as required.  I will conduct the trial in accordance with the principles of ICH Good Clinical 
Practice and the Declaration of Helsinki. 
I will maintain as confidential all written and verbal information provided to me by the Sponsor, including 
but not limited to, the protocol, case report forms, investigator’s brochure, material supplied at investigator 
meetings, minutes of teleconferences, etc.  Such materials will only be provided as necessary to site 
personnel involved in the conduct of the trial, involved IRBs or local regulatory authorities. 
I will obtain written informed consent/ assent from each prospective trial subject or each prospective trial 
subject’s legal representative prior to conducting any protocol-specified procedures.  The Informed 
Consent/Assent 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.   
 
Investigator Signature: 
 
 
____________________________________ 
________________________ 
Investigator signature 
 
Date 
 
 
 
____________________________________ 
Investigator printed name 
 
 
 
 
 
 
 


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Aclaris Therapeutics, Inc. 
 
 
Page 4 of 82 
Version 9.0, Date: 09APR2019 
1. AMENDMENT HISTORY 
Protocol Version 2.0 dated 26JUL2017 was implemented prior to initiation of the study.  Protocol Version 
3.0 was amended to extend treatment from 3 to 6 months, add visits at Months 4, 5, and 6, allow subjects 
who normally shave their scalp to shave their scalp and maintain the same hair style, as long as they refrain 
from shaving at least 1 week prior to the study assessments or longer at the discretion of the investigator 
based on visible scalp hair growth and to add a requirement for sexually active males to use a barrier method 
of birth control (Inclusion criterion #13).  
 
Protocol Version 4.0 dated 26APR2018 was amended to:  
• 
clarify the definition of stable AA,  
• 
update the ANC and platelet criteria to less than the lower limit of normal,  
• 
add a 6-month washout period for JAK inhibitors (oral and topical),  
• 
reduce the timeframe a WOCBP should be on highly effective birth control from 90 days to 30 
days prior to study entry, given the proven onset of contraceptive effectiveness, 
• 
update Sponsor address,  
• 
add Sponsor Safety Monitor Contact Information,  
• 
minor clarifications and typographical edits, 
• 
addition of the Global Impression of Change (Physician and Subject) Assessment. 
 
Protocol Version 5.0 dated 11JUN2018 was amended to allow enrollment of a broader range of subjects 
with AA for whom there is a hypothesis to support an efficacious response to ATI-50002 by: 
• 
Decreasing the minimum SALT score from 30% hair loss to 15% hair loss, 
• 
Increasing the maximum duration of the current episode of AA from 7 years to 12 years, 
• 
Allowing the inclusion of subjects with ophiasis pattern of AA. 
• 
Changing the primary efficacy analysis from the “change from baseline” to the “mean relative 
percent change from baseline” in the SALT score at Week 24 (Visit 10). 
• 
Adding that the statistical analysis will include a stratification of subjects based on baseline 
SALT score, where the number and range of each stratum will be determined by a blinded review 
of the distribution of the baseline scores, conducted prior to database unblinding. 
• 
Revising the secondary analysis: 
- 
Changed the “mean change from baseline” to the “mean relative percent change from 
baseline” in the ALODEX score 
- 
Added the mean change from baseline in SALT score and ALODEX score at Week 24 (Visit 
10)  
- 
Clarified that the proportion of subjects achieving ≥50% hair regrowth compared with 
baseline will be analyzed using a separate model for SALT and for ALODEX scores 
• 
Updating the number of sites from approximately 20 to 27. 
 
Protocol Version 6.0 dated 08AUG2018 was amended to change the area of the study medication 
application from the areas of the scalp with patchy alopecia areata including a ½ inch margin around 
the patchy areas to application to the entire scalp.  Subjects will apply up to 4-mLs, twice-daily; once 
in the morning and approximately 12 hours. 
   
Protocol Version 7.0 (Amendment 6, dated 10AUG2018) was amended to allow inclusion of subjects 
≥ 12 years old (previously ≥ 18 years old). 
 
Administrative Letter #3 dated 28AUG2018 provided the previously approved study medication 
application instructions for use when applying drug to the patchy areas only.  Administrative Letter 
#4 dated 06SEP2018 clarified the study medication allocation instructions for subjects < 18 years of 
age.  Administrative Letter #5 dated 14SEP2018 updated the title to include adolescents.   


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 5 of 82 
Version 9.0, Date: 09APR2019 
 
Protocol Version 8.0 (Amendment 7, dated 26SEP2018) allowed subjects who complete the 
double-blind portion of the study to have the option of enrolling into a long-term open-label 
extension (OLE) period to apply ATI-50002 Topical Solution 0.46%.  The purpose is to allow 
subjects who may have received placebo an opportunity to apply active treatment and subjects on 
active treatment to extend the treatment period.  Amendments 1-8 have been incorporated into 
the final protocol dated 09APR2019 
 
 
2. AMENDMENT RATIONALE 
 
The primary purpose of the update to Protocol Version 9.0 (Amendment 8, dated 09APR2019) is 
to clarify that the primary analysis would be conducted on the ITT population.  Additionally, 
other changes to the statistical methods are detailed in the following table. 
   
3. PROTOCOL CHANGES 
Protocol 
Version 
9.0 
Date 
Section 
Revisions 
09APR2019 
Title Page 
Updated Safety Monitor  
Endpoints 
-Synopsis 
-Statistical Sections 
Clarified that the primary endpoint and the secondary endpoints 
are “Percent change from baseline” and not “Mean relative 
percent change from baseline”. 
Sample Size and 
Power Calculations 
-Synopsis,  
-Section 11.1 
Added a power statement describing the treatment difference 
(24-points) that we can detect with 80% power. 
Statistical Methods,  
-Synopsis 
-Section 11.4.1 
Specified that the primary analysis would be on the ITT 
population, using LOCF for missing data and based upon a 
mixed effect model repeated measures (MMRM). 
Secondary Efficacy 
Analyses 
-Synopsis 
-Section 11.4.2 
Deleted:  Dichotomous variables will be analyzed using Chi-
Square tests. Ordinal and continuous variables will be analyzed 
using appropriate Analysis of Variance models. 
Safety Data 
-Synopsis 
-Section 11.5 
 
Deleted:  Overall incidence of adverse events will be compared 
between groups using a chi-square test. 
Section 11.4 
Deleted the statement that the PP population would be used for 
all efficacy analyses. 
Section 11.4.2 
 
Included a secondary sensitivity analysis on the primary 
endpoint using the PP population. 
 
Added secondary responder efficacy endpoints to be specified 
in the SAP 
 
Specified that all secondary efficacy endpoints would be 
analyzed using the ITT population 
 
 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 6 of 82 
Version 9.0, Date: 09APR2019 
 
SYNOPSIS 
Protocol Number: 
ATI-50002-AA-201 
 
 
Protocol Title:  
A Randomized, Double-Blind, Vehicle-Controlled Multicenter Study to 
Evaluate the Safety, Tolerability and Efficacy of ATI-50002 Topical 
Solution Administered Twice-Daily for 6 Months in Adolescents and Adult 
Subjects with Stable Patchy Alopecia Areata with Optional Long-Term 
Open-Label Extension 
Sponsor: 
Aclaris Therapeutics Inc. 
 
Phase of Development:  Phase 2 
 
 
Study Medication Description: 
Double-Blind: ATI-50002 Topical Solution, 0.46%, ATI-50002 Topical Solution, 0.12% or Vehicle 
Topical Solution 
Open-Label:  ATI-50002 Topical Solution, 0.46% 
Study Objectives: 
Primary: 
• 
To assess safety, tolerability and efficacy of ATI-50002 Topical Solution, 0.46% and 0.12% 
compared to vehicle in subjects with stable patchy alopecia areata (AA) 
Secondary: 
• 
To evaluate the psychometric performance of the key clinical outcome assessments and 
questionnaires with respect to reliability, construct-related validity, and sensitivity to change 
• 
To generate score interpretation estimates for the clinical outcome assessments to guide the 
definition of responders in pivotal trials 
Exploratory: (Select Sites Only) 
• 
At select clinical sites, to explore the effects of ATI-50002 induced Janus kinase (JAK) 1/3 
inhibition on the Alopecia Areata Disease Activity Index (ALADIN) scores, peribulbar infiltrate, 
and other inflammatory biomarkers  
Long-term Objective: 
To assess the safety, tolerability and efficacy of ATI-50002 Topical Solution, 0.46% in subjects with 
stable patchy alopecia areata. 
 
Study Design: 
Double-blind Period:  This Phase 2, multicenter, randomized study is designed to evaluate the safety, 
tolerability and efficacy of ATI-50002 Topical Solution in subjects with stable patchy alopecia areata 
(AA).  Subjects will be required to have a clinical diagnosis of alopecia areata (AA) with at least 15% 
up to 95% total scalp hair loss for a duration of at least 6 months up to and including 12 years.  A total 
of 120 subjects will be randomized.  Subjects will be randomized to a 1:1:1 ratio: 
• 
ATI-50002 Topical Solution, 0.46%, BID for 24 weeks (6 months)  
• 
ATI-50002 Topical Solution, 0.12%, BID for 24 weeks (6 months) 
• 
Vehicle Topical Solution BID for 24 weeks (6 months) 
During the screening period, subjects will be assessed for eligibility into the study.  Subjects will apply 
up to 4 mLs of study medication to the entire scalp twice a day for 24 weeks.   Assessment of response 
to treatment will be performed at Week 4 (Visit 5), Week 8 (Visit 6), Week 12 (Visit 7), Week 16 
(Visit 8), Week 20 (Visit 9), Week 24 (Visit 10), and post-treatment Week 28 (Visit 11).  Safety and 
tolerability will be evaluated at each study visit by assessment of adverse events and vital signs, and at 
select visits, ECGs and clinical laboratory tests will be completed.  The primary analysis will be 
conducted after all subjects complete the double-blind visits.   
 
 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 7 of 82 
Version 9.0, Date: 09APR2019 
Open-Label Extension (OLE): Subjects who complete Visit 10 or Visit 11 (Week 24 or 28) will be 
eligible to enter a 28 week OLE.  In the OLE, safety, tolerability and efficacy will be assessed.  All 
subjects enrolled in the OLE will apply ATI-50002 Topical Solution, 0.46% to the entire scalp or 
patchy areas with a ½” margin, twice daily for 24 weeks (6 months).  In addition, subjects with 
eyebrow loss may apply study medication to the entire eyebrow(s) twice daily for 24 weeks.  Subjects 
will be followed for safety, tolerability and efficacy as detailed in Section 6.3.  Subjects who decline or 
are not eligible for the OLE should be seen for the Visit 11 (Post-treatment) assessments. Subjects who 
entered the OLE and for administrative reasons had a gap between completion of Visit 10 or Visit 11 
and entry into the open-label should return for the OLE Visit 1 and have the procedures detailed in the 
Schedule of Assessments.   
 
Number of Subjects (planned): 
120 subjects will be enrolled into the study. 
 
Number of Study Sites: 
This study will be conducted at approximately 27 U.S. clinical sites. 
 
Double-blind Period 
Inclusion Criteria: 
Subjects must meet the following criteria to be eligible for participation in the study.   
1. Able to comprehend and willing to sign an Informed Consent/Assent Form (ICF). 
2. Male or non-pregnant, non-nursing female ≥12 years old at the time of informed consent/ 
assent. 
3. Have a clinical diagnosis of stable patchy alopecia areata (AA) defined as no current areas of 
spontaneous regrowth. 
4. Have a Severity of Alopecia Tool (SALT) score of at least 15% up to 95% total scalp hair loss 
determined by the study investigator at baseline. 
5. Have an assessment of “no hair” or “a little hair” in the target scalp patch based on both the 
Clinician and Subject Alopecia Scalp Appearance Assessment (AAA). 
6. Have a duration of the current episode of scalp hair loss of a minimum of 6 months and a 
maximum of 12 years.  
7. If a woman of childbearing potential (WOCBP), must have a negative serum pregnancy test at 
Screening (Visit 1) and a negative urine pregnancy test at Baseline (Visit 2) and agree to: use a 
highly effective method of birth control for the duration of the study; not be planning a 
pregnancy during the study duration and use contraception for 30 days after last application of 
study medication (Refer to Section 10). 
8. Be in good general health and free of any known disease state or physical condition which, in 
the investigator’s opinion, might impair evaluation of the subject or which might expose the 
subject to an unacceptable risk by study participation. 
9. Be willing to maintain the same hair style throughout the study period. Subjects who shave 
their scalp must be willing to refrain from shaving their scalp for at least one week or longer 
prior to each study visit, as determined by the investigator based on visible scalp hair growth. 
Hair trimming outside the treatment areas to maintain the current hair style is permitted. 
10. Be willing and able to follow all study instructions and to attend all study visits. 
11. Subjects taking hormonal replacement therapies must be on stable doses for 6 months prior to 
enrollment and remain on the same maintenance dose throughout the study.  
12. Subjects taking thyroid replacement medication must be on stable doses for 6 months prior to 
enrollment and remain on the same maintenance dose throughout the study. 
13. 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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Aclaris Therapeutics, Inc. 
 
 
Page 8 of 82 
Version 9.0, Date: 09APR2019 
Exclusion Criteria: 
Subjects are excluded from this study if any 1 or more of the following criteria is met: 
1. Females who are nursing, pregnant, or planning to become pregnant for the duration of the study 
and up to 30 days after the last application of study medication.  
2. Diffuse alopecia areata. 
3. Concomitant hair loss disorder (by history or physical exam) such as androgenetic alopecia or 
scarring alopecia (e.g., cicatricial alopecia, frontal fibrosing alopecia, etc.). Subjects without a 
prior known history of androgenic alopecia (AGA) or other patterned hair loss disorder who 
exhibit AGA or other patterned hair loss with regrowth during the study will be allowed to 
continue in the study. 
4. Active skin disease on the scalp (such as psoriasis or seborrheic dermatitis) or a history of skin 
disease on the scalp that in the opinion of the investigator would interfere with the study 
assessments of efficacy or safety. 
5. Active scalp trauma or other condition affecting the scalp that, in the investigator’s opinion, may 
affect the course of AA or interfere with the study conduct or evaluations. 
6. The presence of a permanent or difficult to remove hairpiece or wig that will, in the opinion of 
the investigator, interfere with study assessments if not removed at each visit.   
7. History of, or current, severe, progressive or uncontrolled renal, hepatic, gastrointestinal, 
pulmonary, cardiovascular, genitourinary (renal disease) or hematological disease, neurologic 
or cerebral disorders, infectious disease or coagulation disorders that, as determined by the 
Investigator, would preclude participation in and completion of study assessments. 
8. History of, current or suspected systemic or cutaneous malignancy and /or lymphoproliferative 
disease, other than subjects with: a history of adequately treated and well healed and 
completely cleared non-melanoma skin cancers (basal or squamous cell carcinoma) treated 
successfully at least 1 year prior to study entry with no evidence of disease.   
9. Evidence of active or latent bacterial (including tuberculosis) or viral infections at the time of 
enrollment, or history of incompletely treated or untreated tuberculosis. Subjects who have 
completed therapy for latent tuberculosis may participate.  
10. History of serious local infection (e.g., cellulitis, abscess) or systemic infection including but not 
limited to a history of treated infection (e.g., pneumonia, septicemia) within 3 months prior to 
baseline. Subjects on an antibiotic for a nonserious, acute local infection must complete the 
course prior to enrollment into the study. 
11. Positive for HIV, Hepatitis B or C.  Subjects with serologic evidence of Hepatitis B vaccination 
(Hep B surface Ab without the presence of Hep B surface Ag) will be allowed to participate. 
12. Herpes zoster or cytomegalovirus (CMV) that resolved less than 2 months before study 
enrollment. Subjects with a history of frequent outbreaks of Herpes Simplex Virus (defined as 4 
or more outbreaks a year). 
13. Clinically significant laboratory abnormalities at screening that, in the opinion of the 
Investigator, would make the subject a poor candidate for the study.   
14. Subjects with absolute neutrophil count <1,800/mL, or platelet count <130,000/mL. 
15. Subject unable to comply with the following required washout periods: 
Therapy/Medication 
Washout Period 
Systemic Therapies 
Disease Modifying Anti-Rheumatic Drugs (DMARDS), Biologics or 
immunosuppressants, such as: anakinra, adalimumab, azathioprine, 
corticosteroids, cyclosporine, etanercept, infliximab, methotrexate, TNF 
inhibitors, ustekinumab 
1 month or 5 half-lives 
whichever is greater 
Plaquenil 
2 months 


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Aclaris Therapeutics, Inc. 
 
 
Page 9 of 82 
Version 9.0, Date: 09APR2019 
JAK inhibitors (oral or topical) 
6 months 
Intralesional Steroids (Scalp) 
1 month 
Anthralin, bimatoprost, corticosteroids, diphencyprone, 
diphenylcycloprophenone (DPCP), Squaric acid dibutylester (SADBE), 
minoxidil, pimecrolimus, tacrolimus 
1 month 
Phototherapy, Laser Therapy, Excimer Laser 
3 months 
  
16. Participation in an investigational drug or device trial in which administration of an 
investigational drug or device occurred within 30 days or 5 half-lives (whichever is longer) of 
Screening (Visit 1).  Subjects who have participated in a study of an investigational drug, device 
or biologic agent for alopecia areata within 1 year of screening will be eligible to participate only 
with individual permission from the Medical Monitor. 
17. Sensitivity to any of the ingredients in the study medications. 
18. History of or current alcohol or drug abuse within 2 years of assessment for study enrollment. 
19. Unwillingness to refrain from weaves, hair extensions, or shaving of the scalp for at least one 
week or longer prior to each study visit, as determined by the investigator based on visible scalp 
hair growth for the duration of the study. 
20. Screening ECG findings of: 
• 
QTcF >450msec for males or >470msec for females (use of the ECG algorithm is 
acceptable for this purpose) 
• 
Clinically Significant Heart rate < 45 or Heart Rate > 100 beats/minute 
• 
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 
 
Open-Label Extension 
Inclusion Criteria: 
1. Subject must be able to comprehend and willing to sign the OLE Informed Consent/Assent 
Form (ICF). 
2. Subject must continue to meet the entry criteria from the double-blind period.  The SALT score 
and duration of disease are based on the double-blind period baseline visit. 
3. Subject has not experienced any clinically significant AEs, SAEs or tolerability issues that met 
study discontinuation criteria in the double-blind period. 
4. Subject is capable of regrowing scalp hair in the opinion of the investigator. 
5. WOCBP must have a negative UPT at entry into OLE. 
 
Duration of Treatment 
Double-blind Period 
The duration of the screening period could be up to 30 days.  Once randomized, the maximum duration 
of study treatment is from Baseline (Visit 2) to the Post-treatment follow-up visit at Week 28 (Visit 11) 
is anticipated to be a maximum of 200 days (197 days + 3-day window). 
 
 
 


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Page 10 of 82 
Version 9.0, Date: 09APR2019 
Open-Label Extension 
The maximum duration of the of study treatment in the OLE is 176 days (169 days + 7-day window).  
The maximum duration of the study participation from entry into the OLE to completion of the post-
treatment follow up visit is 204 days.   
 
Endpoints 
 
Primary Efficacy: 
• 
Percent change from baseline in the Severity of Alopecia Tool (SALT) score at Week 24 (Visit 
10), also described as mean percent regrowth   
Secondary Efficacy: 
• 
Percent change from baseline in the Alopecia Density and Extent Score (ALODEX) score at Week 
24 (Visit 10), also described as mean percent regrowth 
• 
Mean change from baseline in SALT score at Week 24 (Visit 10) 
• 
Mean change from baseline in ALODEX score at Week 24 (Visit 10) 
• 
Proportion of subjects in each treatment arm achieving ≥ 50% hair regrowth compared with baseline 
using a separate model for SALT and for ALODEX scores 
• 
Change from baseline in the Alopecia Scalp Appearance Assessment (AAA) for Patchy AA 
(Patient-reported outcome [PRO]) at Week 24 (Visit 10)  
• 
Change from baseline in the Alopecia Scalp Appearance Assessment (AAA) for Patchy AA 
(Clinician-reported outcome [ClinRO]) at Week 24 (Visit 10) 
• 
Change from baseline in the Physicians Global Impression of Severity (PhGIS) of Patchy AA at 
Week 24 (Visit 10)  
• 
Change from baseline in the Subject Global Impression of Severity (SGIS) of Patchy AA at 
Week 24 (Visit 10) 
• 
Change from baseline in the subject reported Alopecia Impact Assessment (AIA) at Week 24 
(Visit 10) 
• 
Subject Global Impression of Treatment Satisfaction at Week 24 (Visit 10) 
• 
Change in Dermatology Life Quality Index (DLQI) total score between Baseline and Week 24 
(Visit 10) 
• 
Global Impression of Change (Clinician and Subject) at Week 24 (Visit 10) 
Exploratory: 
• 
At select clinical sites, the change from baseline in the effects of ATI-50002 induced Janus kinase 
(JAK) 1/3 inhibition on the ALADIN scores, peribulbar infiltrate and other inflammatory 
biomarkers 
 
Safety: 
• 
Safety variables to be assessed include: adverse events, clinical laboratory tests (hematology, 
clinical chemistry, and urinalysis), vital sign measurements (systolic and diastolic blood pressures, 
respiration rate, heart rate, and oral body temperature), and electrocardiograms. 
Long-term: 
• 
Safety variables, efficacy variables [(change from baseline in SALT, ALODEX at long-term 
visits), (change from baseline in AAA-SR, AAA-CR, SGITS)].  
 
Study Medication Administration 
Subjects will apply up to a maximum of 4 mL of topical solution to the entire scalp twice-daily as 
directed.  
Prior to amendment 5, subjects were instructed to treat patches of active alopecia areata and not the 
entire scalp.  Subjects who signed the ICF prior to amendment 5 and do not consent to twice-daily 
applications to the entire scalp may continue in the study.  These subjects should be given the option to 


Protocol: ATI-50002-AA-201 
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Page 11 of 82 
Version 9.0, Date: 09APR2019 
apply the study medication to the entire scalp at night only, and the patchy areas during the day or to 
the patchy alopecia areas and a ½” margin around the areas twice-daily.  The areas being treated must 
be identified in the source documentation and the eCRF as; patchy areas only twice-daily, entire scalp 
twice-daily or patchy areas only once-daily, and entire scalp once-daily. 
In the OLE, in addition to applying study medication to the entire scalp twice-daily (or patchy areas 
with a ½” margin if the subject did not agree to apply to the entire scalp) subjects with eyebrow loss 
will be allowed to apply a thin film of study medication twice-daily to the affected eyebrow(s) as 
directed. 
 
Statistical Methods 
The primary analysis will be conducted when all subjects have completed the double-blind period. 
 
Sample Size/ Power Calculations 
The planned sample size is 120 subjects.  Sincethis is the first multicenter study evaluating the effect of 
ATI-50002 Topical Solution in subjects with stable patchy alopecia areata, the sample size was based 
upon feasibility issue rather than on a formal power calculation.  However, data from 120 subjects (40 
per group), utilizing LOCF for missing data, provides 80% power to detect a 24-point difference 
in percent change from baseline in SALT score between any two treatment groups.  This power 
computation was based upon the assumed standard deviation of 38%.  Data from a previous 
study NCT02197455 showed that the standard deviation in percent change from baseline in the 
SALT score is 30.3%.  The 38% standard deviation assumption used for this power computation 
was chosen to account for the increase in variance due to the lower baseline SALT entry criteria 
for this study as compared to NCT02197455. 
 
 
Statistical Methods 
The primary efficacy variable will be the percent change from baseline in the SALT score at Week 24 
(Visit 10).  This represents the percentage of hair regrowth.  It will be calculated as the mean of the 
changes from baseline (Visit 2) SALT score to Week 24 (Visit 10) SALT score, divided by the baseline 
SALT score and expressed as a percentage.  Missing data for the primary endpoint will be imputed using 
Last Observation Carried Forward (LOCF) methodology.  The analysis will be conducted on the relative 
percent change from baseline over time including all visits using a mixed effect modelrepeated measures 
(MMRM).  The adjusted mean (LS Mean) for percent change from baseline in the SALT score at each 
visit, estimated from the MMRM, with the estimated standard error and 95% confidence interval (CI), 
will be presented in tabular and graphic format. The difference in the adjusted means between treatment 
groups and the associated 95% CI of the difference will be provided.  No adjustment for multiplicity will 
be made.  The model will include fixed effect terms for treatment, study visit, baseline SALT score group 
(<50, >=50), and treatment by SALT group interaction.  The primary analysis will be based on the Intent-
to-Treat (ITT) population.  Statistical significance for primary efficacy endpoint will be declared if at 
least one treatment group comparison at the Week 24 visit has a two-sided p-value less than or equal to 
0.05. 
    
Secondary Efficacy Analyses 
The secondary efficacy endpoints include: the percent change from baseline in the ALODEX score 
(percent regrowth); the mean change from baseline in SALT and the mean change from baseline in 
ALODEX, the proportion of subjects achieving a ≥ 50% hair regrowth compared with baseline using a 
separate model for SALT and for ALODEX scores; change from baseline in the AAA (Clinician and 
Subject), PhGIS, SGIS, AIA, treatment satisfaction questionnaires; and DLQI.  Global Impression of 
Change (Clinician and Subject) at Week 24 (Visit 10) will be used in the psychometric evaluation of the 
scores from the AAA (CR and SR), respectively.  The mean percent change in ALODEX score analysis 


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will use the same methodology as specified for the primary efficacy analysis.  Other parameters will be 
analyzed as detailed in the statistical analysis plan.  
  
Data collected in this trial will be used to evaluate the psychometric properties of the newly developed 
patient-reported and clinician-reported outcome (PRO and ClinRO) questionnaires.  A measurement-
focused statistical analysis plan will detail the data analytic strategy used to achieve the measurement 
property and score interpretation objectives. The anticipated psychometric evaluation analyses for the 
newly developed PRO and ClinRO questionnaires may include the following: score description, score 
reliability, score construct-related validity and score interpretation. 
 
 
Exploratory Biomarker Analyses (Select Sites Only) 
ALADIN Scores (Select Sites Only)           
The cytotoxic T lymphocyte infiltration (CTL), Interferon (IFN-gamma), and hair keratin (KRT) 
ALADIN scores will be calculated for each scalp biopsy sample as described in Xing et al, 2014, 
Jabbari 2016.  Change in ALADIN scores within individual subjects will be assessed between Baseline 
(Visit 2) and Week 4 (Visit 5), and Week 24 (Visit 10).   
 
Histology (Select Sites Only) 
Scalp punch-biopsies will be formalin-fixed and paraffin-embedded and will be sectioned both vertically 
and horizontally by a qualified dermatopathologist.  Specimens will be stained with hematoxylin and 
eosin (H&E) for routine histopathologic evaluation that will include (but is not limited to) diagnosis and 
evaluation of the presence, quantity, location, and quality of any hair, hair follicles, and inflammatory 
infiltrate present.  Additionally, immunohistochemical (IHC) stains will be employed to identify immune 
cell populations (e.g., Lymphocytes, cytotoxic T-lymphocytes [CTLs]), and hair-specific keratins.  IHC 
stains to assess inflammatory responses will include (but not be limited to) CD8, HLA-DR and ICAM-
1.  Data will be presented as percent change from baseline in the number of cells/ high power field in 
regions of interest (peribulbar areas) and in percent change from baseline in the number of cells/mm2. 
 
Blood for Immunology (Select Sites Only) 
Blood samples will be stained with cell surface antibodies for fluorescence acquisition cell sorting 
(FACS) analysis.  FACS experiments will allow for assessment of the subset and activation status of 
immune cells involved in AA.  
 
Clinical Correlative Studies (Select Sites Only) 
Previous studies in human AA have reported increased NKG2DL expression and augmented 
expression of IFN response genes in the target hair follicle end organ, and elevated NKG2D expression 
in circulating CD8 T-cells and NK cells (Ito et al, 2008; Petukhova et al, 2010). 
 
The study will include assessment of AA biomarkers at baseline and during treatment to correlate 
treatment and disease status with: 
1. Histological improvement with reduced T-cell peribulbar infiltrates. 
2. Declines in circulating and peribulbar CD8+NKG2D+ infiltration and in hair follicle NKG2DL 
expression. 
3. Reduced IFN inflammatory biomarkers in the skin and blood. 
 
Safety Data 
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 treatment and Medical Dictionary for Regulatory Activities (MedDRA) System Organ 


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Class. Vital signs and clinically significant abnormal laboratory results will also be tabulated and 
presented by treatment group.  
 
Data from all randomized and treated subjects will be presented and summarized. Safety summaries by 
study treatment group will include listings by study medication of adverse events incidences within 
each MedDRA System Organ Class, and changes from pre-application values in vital signs. Adverse 
event summaries will be presented by study medication showing the proportion of subjects 
experiencing adverse events, both overall and by MedDRA System Organ Class.  
 
 
 
 


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TABLE OF CONTENTS 
 
SYNOPSIS ......................................................................................................................... 6 
 
INTRODUCTION ........................................................................................................... 21 
 
Summary ....................................................................................................................................... 21 
 
STUDY RATIONALE .................................................................................................... 24 
 
Study Rationale ............................................................................................................................. 24 
 
STUDY OBJECTIVES ................................................................................................... 26 
 
Primary Objective ........................................................................................................................ 26 
 
Secondary Objectives ................................................................................................................... 26 
 
Exploratory (Select Sites Only): .................................................................................................. 27 
 
Long-term Objective .................................................................................................................... 27 
 
SELECTION AND DISPOSITION OF STUDY POPULATION .............................. 27 
 
Number of Subjects and Study Sites ........................................................................................... 27 
 
Study Population Characteristics ................................................................................................ 27 
 
Double-Blind Inclusion Criteria .................................................................................................. 27 
 
Double-Blind Exclusion Criteria ................................................................................................. 28 
 
Open-Label Extension .................................................................................................................. 30 
5.5.1. 
OLE Entry Criteria ................................................................................................................... 30 
 
Previous and Concomitant Medications and Therapies ........................................................... 30 
5.6.1. 
Permitted Concomitant Medications and Over the Counter Products (OTC) .................... 31 
5.6.2. 
Prohibited and/ or Restricted Medications .............................................................................. 31 
 
Subject Identifier (SI) ................................................................................................................... 32 
 
Replacement Subjects ................................................................................................................... 32 
 
Subject Withdrawal Criteria ....................................................................................................... 32 
 
Study Termination ........................................................................................................................ 33 
 
INVESTIGATIONAL PLAN ......................................................................................... 33 
 
Overall Study Design .................................................................................................................... 33 
 
STUDY PROCEDURES .............................................................................................................. 33 
 
Schedule of Assessments .............................................................................................................. 34 
 
Duration of the Study ................................................................................................................... 38 
 
STUDY TREATMENT .................................................................................................. 38 
 
Investigational Study Medication ................................................................................................ 38 
 
Subject Randomization ................................................................................................................ 38 
 
Application of Study Medication ................................................................................................. 39 


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7.3.1. 
Subjects Who Signed Consent Prior to Amendment 5 ........................................................... 40 
 
Study Medication Weights ........................................................................................................... 40 
 
Treatment Compliance ................................................................................................................. 40 
 
Dose Modification ......................................................................................................................... 40 
 
Study Medication Accountability ................................................................................................ 41 
 
Other Study Supplies.................................................................................................................... 41 
 
Blinding ......................................................................................................................................... 41 
7.9.1. 
Unblinding the Study Medication ............................................................................................. 41 
 
Study Medication Packaging, Labeling, Storage and Security ................................................ 42 
 
STUDY ASSESSMENTS ............................................................................................... 42 
 
Assessments of Efficacy ................................................................................................................ 43 
8.1.1. 
Severity Alopecia Tool (SALT) Score ...................................................................................... 43 
8.1.2. 
Alopecia Density and Extent Score (ALODEX) ...................................................................... 43 
8.1.3. 
Alopecia Target Scalp Patch Identification ............................................................................. 43 
8.1.4. 
Alopecia Appearance Assessment (AAA) for Patchy AA: Clinician and Subject ................ 43 
8.1.5. 
Global Impression of Severity ................................................................................................... 44 
8.1.6. 
Global Impression of Change.................................................................................................... 44 
8.1.7. 
Hair Quality Assessments .......................................................................................................... 45 
8.1.7.1 
Hair Pull Test ........................................................................................................................... 45 
 
Biomarker Assessment (Selected Sites only) .............................................................................. 45 
8.2.1. 
Scalp Biopsy (Selected Sites Only) ............................................................................................ 46 
8.2.2. 
Blood for Immunologic Evaluation (T-cells) (Selected Sites Only) ....................................... 46 
 
Assessment of Subject Satisfaction and Patchy AA Impact ..................................................... 46 
8.3.1. 
Subject Global Impression of Treatment Satisfaction ............................................................ 46 
8.3.2. 
Alopecia Impact Assessment (AIA):  Subject Rating ............................................................. 46 
8.3.3. 
Dermatology Life Quality Index (DLQI) ................................................................................. 46 
 
Assessment of Safety ..................................................................................................................... 46 
8.4.1. 
Vital signs .................................................................................................................................... 47 
8.4.2. 
Physical Examination ................................................................................................................ 47 
8.4.3. 
Clinical Laboratory Assessments ............................................................................................. 47 
8.4.4. 
Pregnancy tests ........................................................................................................................... 48 
8.4.5. 
ECGs ........................................................................................................................................... 48 
 
Other Assessments ........................................................................................................................ 49 
8.5.1. 
Demographics, Medical History and Alopecia Areata History.............................................. 49 


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8.5.2. 
Photographic Assessment .......................................................................................................... 49 
 
ADVERSE EVENTS ....................................................................................................... 49 
 
Definitions ..................................................................................................................................... 50 
9.1.1. 
Adverse events (AE) ................................................................................................................... 50 
9.1.2. 
Serious adverse event (SAE) ..................................................................................................... 50 
9.1.3. 
Unexpected adverse event ......................................................................................................... 51 
9.1.4. 
Adverse event reporting period ................................................................................................ 51 
9.1.5. 
Severity........................................................................................................................................ 51 
9.1.6. 
Relationship to study medication .............................................................................................. 51 
 
Reporting Procedures ................................................................................................................... 52 
9.2.1. 
Procedures for reporting adverse events ................................................................................. 52 
9.2.2. 
Procedure for reporting a serious adverse event .................................................................... 52 
9.2.3. 
Safety Monitoring Discontinuation Criteria ............................................................................ 53 
9.2.4. 
Study Medication Interruption and Discontinuation Criteria ............................................... 54 
9.2.4.1 
Study Medication Interruption .............................................................................................. 54 
9.2.4.2 
Study Medication Discontinuation ......................................................................................... 54 
 
PREGNANCY ................................................................................................................. 55 
 
Definition of Women of Child Bearing Potential (WOCBP) .................................................... 55 
 
Highly Effective Methods of Birth Control ................................................................................ 55 
 
STATISTICAL ANALYSES ......................................................................................... 56 
 
Sample Size and Power Calculations .......................................................................................... 57 
 
Analysis Populations..................................................................................................................... 57 
 
Demographic and Baseline Characteristics ................................................................................ 57 
 
Efficacy Analyses .......................................................................................................................... 57 
11.4.1. 
Primary Efficacy Analyses ........................................................................................................ 57 
11.4.2. 
Secondary Efficacy Analyses ..................................................................................................... 58 
 
Safety Analyses ............................................................................................................................. 58 
 
Open-Label Extension Analyses .................................................................................................. 58 
 
Exploratory Biomarker Analyses (Select Sites Only) ................................................................ 59 
11.7.1. 
ALADIN Scores (Select Sites Only) .......................................................................................... 59 
11.7.2. 
Scalp Biopsy for Histology and Immunology (Select Sites Only) .......................................... 59 
11.7.3. 
Blood for Immunology (Select Sites Only) ............................................................................... 59 
11.7.4. 
Clinical Correlative Studies (Select Sites Only) ...................................................................... 59 
 
TRAINING, MONITORING, DATA MANAGEMENT AND QUALITY 
ASSURANCE .............................................................................................................................. 59 


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Training ......................................................................................................................................... 59 
 
Monitoring ..................................................................................................................................... 60 
 
Data Management......................................................................................................................... 60 
 
Quality Assurance......................................................................................................................... 60 
 
ETHICS AND GENERAL STUDY CONDUCT CONSIDERATIONS .................... 61 
 
Institutional Review Board (IRB)/Ethics Committee (EC) ....................................................... 61 
 
Ethical Conduct of the Study ....................................................................................................... 61 
 
Subject Information and Consent/ Assent .................................................................................. 61 
 
Study Conduct and Protocol Amendments ................................................................................ 61 
 
Regulatory Documents ................................................................................................................. 62 
 
Contractual Requirements ........................................................................................................... 62 
 
Data Collection and Archiving .................................................................................................... 62 
13.7.1. 
Data collection ............................................................................................................................ 62 
13.7.2. 
Source documentation ............................................................................................................... 62 
13.7.3. 
Archiving .................................................................................................................................... 62 
 
REFERENCES ................................................................................................................ 64 
:  Subject Instructions for Study Medication Application to the 
Patchy Areas of the Scalp ........................................................................................................... 66 
:  Parent/ Subject Instructions for Study Medication Application to 
the Entire Scalp ........................................................................................................................... 68 
:  Parent/ Subject Instructions for Study Medication Application to 
the Eyebrow during the Open-Label Extension ....................................................................... 70 
:  Alopecia Areata History .................................................................................. 72 
:  Fitzpatrick’s Skin Type Chart ........................................................................ 73 
:  Alopecia Scalp Appearance Assessment for AA Patchy (AAA) 
(Subject) 
........................................................................................................................... 74 
:  GLOBAL IMPRESSION OF SEVERITY - Subject .................................... 75 
:  SUBJECT SATISFACTION QUESTIONNAIRE........................................ 76 
:  ALOPECIA IMPACT ASSESSMENT .......................................................... 77 
:  DERMATOLOGY LIFE QUALITY INDEX ............................................. 79 
:  Select Sites Only- Scalp Biopsy ..................................................................... 81 
:  Subject Global Impression of Change (SGIC) ............................................ 82 
 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Term 
AA 
Alopecia Areata 
AAA 
Alopecia Scalp Appearance Assessment 
Ab 
Antibody 
AE  
Adverse Event 
Ag 
Antigen 
AGA 
Androgenic Alopecia 
AIA 
Alopecia Impact Assessment 
ALADIN 
Alopecia Areata Disease Activity Index 
ALODEX 
Alopecia Density and Extent Score 
ALT 
Alanine aminotransferase 
ANC 
Absolute Neutrophil Count 
ANOVA 
Analysis of Variance 
AST 
Aspartate Aminotransferase 
AT 
Alopecia Totalis 
AU 
Alopecia Universalis 
BCC 
Basal Cell Carcinoma 
BID, b.i.d. 
Twice-daily 
BUN 
Blood Urea Nitrogen 
°C 
Degrees Centigrade 
CD 
Cluster of Differentiation 
CI 
Confidence Interval 
ClinRO 
Clinician Reported Outcome 
CMV 
Cytomegalovirus 
CR 
Clinician Rating 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
CTL 
Cytotoxic T-lymphocytes 
dL 
deciliter 
DLQI 
Dermatology Life Quality Index 
DMARDs 
Disease Modifying Anti-Rheumatic Drugs 
DMSO 
Dimethyl Sulfoxide 
DPCP 
Diphenylcyclopropenone 
e.g.  
for example (Latin; exempla gratia) 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
°F 
Degrees Fahrenheit 


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Abbreviation 
Term 
FACS 
Fluorescence Acquisition Cell Sorting 
FDA 
Food and Drug Administration 
G/g 
Gram 
GCP 
Good Clinical Practice 
HCl 
Hydrochloride 
HDL 
High Density Lipoprotein 
HepB 
Hepatitis B 
HCV 
Hepatitis C Virus 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
Human Immunodeficiency Virus 
H&E 
Hematoxylin and Eosin 
HLA-DR 
Human Leukocyte Antigen- antigen D Related 
ICAM-1 
Intercellular Adhesion Molecule 1 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization  
i.e.  
that is (Latin; id est) 
IFN 
Interferon 
IHC 
Immunohistochemical  
IL 
Interleukin 
IUD 
Intrauterine Device 
IUS 
Intrauterine Hormone Releasing System 
ITT 
Intent-to-Treat 
IRB 
Institutional Review Board 
JAK 
Janus Kinase  
KER 
Hair keratin panel 
KRT 
Hair Keratin 
LDH 
Lactate dehydrogenase 
LDL 
Low density lipoprotein 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHC 
Major Histocompatibility Complex 
mL 
Milliliter 
Mm 
Millimeter 
MMRM 
Mixed Effect Model Repeated Measures 
NCS 
Not Clinically Significant 
NK/ NKG 
Natural Killer/ Natural Killer Group 
NKG2D 
A Transmembrane Protein 
NMSC 
Nonmelanoma Skin Cancer 
OTC 
Over-The-Counter 
PDT 
Photodynamic Therapy 


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Abbreviation 
Term 
PEG 
Polyethylene glycol 
PhGIC 
Physician Global Impression of Change 
PhGIS 
Physicians Global Impression of Severity 
PP 
Per-protocol 
PRO 
Patient-Reported Outcome 
PUVA 
Psoralen and Ultraviolet A 
SADBE 
Squaric Acid Dibutyl Ester 
SAE 
Serious Adverse Event 
SALT 
Severity of Alopecia Tool 
SCC 
Squamous Cell Carcinoma 
SGIC 
Subject Global Impression of Change 
SGIS 
Subject Global Impression of Severity 
SGITS 
Subject Global Impression of Treatment Satisfaction 
SI 
Subject identifier 
SN 
Subject Number 
SOP 
Standard Operating Procedure 
SR 
Subject Rating 
STAT 
Signal Transducer and Activator of Transcription 
T3, T4, TSH 
Triiodothyronine, Thyroxine, Thyroid Stimulating Hormone 
TIBC 
Total Iron Binding Capacity 
TEAE 
Treatment Emergent Adverse Event 
TNF 
Tumor Necrosis Factor 
Tyk2 
Tyrosine Kinase 2 
UPT 
Urine Pregnancy Test 
US 
United States 
UVA 
Ultraviolet A  
UVB 
Ultraviolet B 
WBC 
White Blood Cell 
WOCBP 
Women of childbearing potential  


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INTRODUCTION 
Aclaris Therapeutics, Inc. is developing ATI-50002 Topical Solution for the treatment of stable 
patchy alopecia areata.  ATI-50002 is a potent highly selective inhibitor of Janus kinase 1 (JAK1) 
and Janus kinase 3 (JAK3). 
 
 
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, 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 assessments (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 
topical immunotherapy- typically with the topical contact sensitizers diphenylcycloprophenone 
(DPCP), squaric acid dibutyl ester (SADBE), or treatment with topical anthralin.  While these 


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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 patients. 
 
Immunopathology & Pathophysiology of AA 
Alopecia areata (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 sparser 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 previously 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 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 major histocompatibility complex (MHC) molecules and NKG2D ligands.  


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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 HF 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 and 2017, 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 patchy AA.  Aclaris is also developing ATI-50001 for the treatment of alopecia 
universalis (AU) and alopecia totalis (AT).  ATI-50001 is an oral prodrug that is rapidly converted 
presystemically to ATI-50002, a potent highly selective inhibitor of Janus kinase 1 (JAK1) and 
Janus kinase 3 (JAK3).  This study will evaluate whether or not the topically applied JAK1/JAK3 
inhibitor, ATI-50002, will attenuate both IL-15 and IFN-gamma signaling, thereby blocking re-
activation of CD8+NKG2D+ memory T-cells, and aborting the cytotoxic T-cell inflammatory 
response underlying AA. 
 
In a previous Phase 1 study in healthy volunteers, single ascending oral doses of ATI-50001 of 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 > 1% 
of subjects were abdominal pain (10%), flatulence (7%), diarrhea (6%) and headache (6%).   


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Three subjects showed mildly elevated ALT or AST concentrations, which in two subjects were 
considered not clinically significant.  For the other subject, the mild ALT elevation was reported 
as a treatment emergent adverse event possibly related to the study drug.  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.   
 
 
STUDY RATIONALE  
 
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.   
 
Topical treatment with ATI-50002 Topical Solution on the areas of a patient’s scalp with alopecic 
patches only may result in undertreatment of disease and potentially lead to sub-optimal efficacy.  
Discussion with experts in the treatment of alopecia has led Aclaris to the conclusion that by only 
treating sites of visible disease, areas of sub-clinical, but active disease may be untreated.  These 
sub-clinical patches may either (a) develop into new patches of disease, or (b) harbor a focus of 
inflammation that impacts other sites on the scalp. 
 
Patchy Alopecia Areata can be a frustrating disease, both to the patient and prescriber.  Physicians 
tell of disease that they describe as “whack a mole”, meaning that treatment can be successful in 
one patch, only for new patches to emerge elsewhere.  Reviews describe how regrowth in one 
region of the scalp may be associated with expanding areas of alopecia elsewhere (Pratt, 2017).   
This dynamic picture of disease suggests that areas of seemingly non-active disease likely have 
sub-clinical ongoing auto-immune inflammation.   


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If areas of untreated inflammation are present, the question is whether they can impact the health 
of other areas of scalp. The C3H/HeJ mouse model of alopecia provides strong evidence that 
disease in one area of skin can indeed impact another (McElwee, 1998).  In this model, an alopecia 
phenotype is transmitted when skin from alopecia affected mice is grafted onto normal C3H/HeJ 
mice.  This implies that the inflammatory process at one site can spread and lead to disease at 
another.   Consequently, subjects in this study will be instructed to apply study medication to the 
entire scalp twice-daily to increase the probability that patients with patchy alopecia in ATI-50002-
AA-201 will achieve good efficacy. 
 
This study will evaluate the safety, tolerability and efficacy of ATI-50002 Topical Solution, 0.12% 
and 0.46% compared to vehicle solution applied twice-daily to the entire scalp for 6 months.  In 
addition, at select clinical sites, the study will explore the effects of ATI-50002 induced Janus 
kinase (JAK)1/3 inhibition on the ALADIN scores, peribulbar infiltrate and other inflammatory 
biomarkers from scalp biopsies and blood samples.  The Alopecia Areata Disease Activity Index 
(ALADIN) is a three-dimensional quantitative composite gene expression score that will be used 
in this study to track disease severity and explore signs of response to treatment (Xing et al 2014).  
 
Subjects with patchy scalp hair loss due to AA ranging from 15% to 95% based on the SALT score 
will be included in this study.  In prior published studies, assessment of efficacy of treatment of 
AA was based on hair regrowth as determined by changes in the SALT score (Olsen 2016).  Both 
the SALT and ALODEX scores will be measured electronically using an iPad. The SALT score is 
a measurement based on the SALT I diagram, that quantifies the amount of scalp without any 
hair.  The ALODEX score is a measurement of the amount of scalp with hair loss and is based on 
the SALT II diagram (Olsen, submitted).  The SALT II diagram breaks the scalp surface area from 
the SALT I diagram into 1% scalp surface areas and allows the investigator to assign a density 
rating to each area from 0 = no hair loss to 100 = complete baldness. The ALODEX score is a 
summation of all density ratings in each 1% scalp area.  By assessing hair density in each of the 
1% scalp areas, the use of the SALT II visual aid allows the following to be tracked: amount of 
absolute hair loss (ALODEX score), specific areas of baldness (all 1% areas are numbered), small 
changes in density that may otherwise go undetected with original SALT I score, percentage of 
scalp surface involved with any hair loss and thus needing to be treated topically, new areas of hair 
loss present since baseline of any given treatment, and lesional scoring by identifying target areas.  
 
Hair loss will be quantified using both the SALT and ALODEX assessments at baseline and 
monthly during treatment. The change from baseline in the SALT and ALODEX scores will be 
used to determine hair regrowth.   In addition to the SALT and ALODEX assessment tools, Aclaris 
is developing Clinician and Patient Reported outcome tools (ClinRO and PRO) to assess hair 
regrowth that is clinically meaningful to subjects.  
 
These ClinRO and PRO tools will measure the signs, symptoms, and impacts of AA for use as 
secondary efficacy endpoints.  The following PRO and ClinRO questionnaires designed to 
measure the scalp appearance, the impact and the global satisfaction with treatment from the 
perspective of the patient and the clinician, where appropriate, are included in the protocol: 
• Scalp based appearance PRO and ClinRO 
o Alopecia Scalp Appearance Assessment (AAA) for Patchy AA: Subject Rating 
[SR] 


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o Alopecia Scalp Appearance Assessment (AAA) for Patchy AA: Clinician Rating 
[CR] 
• Impact of alopecia PRO 
o Alopecia Impact Assessment (AIA) 
• Satisfaction with treatment PRO 
o Subject Global Impression of Treatment Satisfaction (SGITS) 
 
Subjects will be enrolled with a range of 15% to 95% hair loss over the entire scalp surface area 
based on the SALT score at baseline.  A baseline ALODEX score will also be obtained but will 
not be used as an inclusion criterion.  The scalp appearance assessments in development (ClinRO 
and PRO) will assess hair loss on a scale from “no hair” to a “full head of hair”.  A target patch 
(identified by the subject as their most bothersome area of hair loss) will be identified at baseline.  
By identifying a target patch, subjects with less extensive hair loss overall can be enrolled using 
the same rating on the Alopecia Scalp Appearance Assessment of “no hair” or “a little hair” at 
baseline.  In addition to the ClinRO and PRO assessments being completed for a target patch, the 
same scalp appearance assessments will be completed for hair loss over a subject’s entire scalp 
surface area. 
 
Because this trial will not be stratified in terms of ethnic background or gender of subjects, there 
is no consistent measure of hair color, caliber, growth rate or hair density that can be used across 
such a diverse population of subjects.  Each of these parameters is intrinsically determined within 
a given subject, and in subjects with more severe hair loss, there will be little to no normal hair at 
the start of the study. Therefore, it will be impossible to establish each subject’s individual baseline 
measure of healthy hair in order to monitor restoration of these parameters over the study.  Further, 
it is not possible to compare these parameters across individuals in the study.   
 
The ALODEX and SALT assessments are based on terminal hair growth.  Another parameter that 
will be considered will be the normalization of exclamation point hairs.  These two features should 
be trackable irrespective of the subjects' intrinsic hair color, caliber or density, and should give a 
meaningful indicator of response to treatment.   
 
The 6-month topical treatment period is supported by the results of 26-week mouse and 39-week 
dog oral toxicity studies with systemic administration and a 6-month update from the 9-month 
minipig study with dermal administration. 
 
 
STUDY OBJECTIVES 
 
Primary Objective 
The primary objective is to assess the safety, tolerability and efficacy of ATI-50002 Topical 
Solution, 0.46% and 0.12% compared to vehicle in subjects with stable patchy alopecia areata 
(AA). 
 
 
Secondary Objectives 
Secondary objectives are: 


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• To evaluate the psychometric performance of the key clinical outcome assessments 
questionnaires with respect to reliability, construct-related validity, and sensitivity to change 
• To generate score interpretation estimates for the clinical outcome assessments to guide the 
definition of responders in pivotal trials 
 
 
Exploratory (Select Sites Only): 
At select clinical sites, to explore the effects of ATI-50002 induced Janus kinase (JAK) 1/3 
inhibition on the ALADIN scores, peribulbar infiltrate and other inflammatory biomarkers. 
 
 
Long-term Objective 
To assess the safety, tolerability and efficacy of ATI-50002 Topical Solution, 0.46% in subjects 
with stable patchy alopecia areata. 
 
 
SELECTION AND DISPOSITION OF STUDY POPULATION 
 
Number of Subjects and Study Sites 
A total of 120 subjects will be enrolled at approximately 27 US sites.  
 
 
Study Population Characteristics 
Male and female subjects, 12 years of age or older, with a clinical diagnosis of stable patchy 
alopecia areata of the scalp, who meet all the inclusion criteria and none of the exclusion criteria, 
will be eligible to enroll in this study.  
 
Double-Blind Inclusion Criteria 
Subjects must meet the following criteria to be eligible for participation in the study: 
1. Able to comprehend and willing to sign an Informed Consent/Assent Form (ICF). 
2. Male or non-pregnant, non-nursing female ≥ 12 years old at the time of informed consent/ 
assent. 
3. Have a clinical diagnosis of stable patchy alopecia areata (AA) defined as no current areas of 
spontaneous regrowth. 
4. Have a Severity of Alopecia Tool (SALT) score of at least 15% up to 95% total scalp hair 
loss determined by the study investigator at baseline. 
5. Have an assessment of “no hair” or “a little hair” in the target scalp patch based on both the 
Clinician and Subject Alopecia Scalp Appearance Assessment (AAA). 
6. Have a duration of the current episode of scalp hair loss of a minimum of 6 months and a 
maximum of 12 years.  
7. If a woman of childbearing potential (WOCBP), must have a negative serum pregnancy test 
at Screening (Visit 1) and a negative urine pregnancy test at Baseline (Visit 2) and agree to: 
use a highly effective method of birth control for the duration of the study; not be planning a 
pregnancy during the study duration and use contraception for 30 days after last application 
of study medication. (Refer to Section 10). 


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8. Be in good general health and free of any known disease state or physical condition which, in 
the investigator’s opinion, might impair evaluation of the subject or which might expose the 
subject to an unacceptable risk by study participation. 
9. Be willing to maintain the same hair style throughout the study period. Subjects who shave 
their scalp must be willing to refrain from shaving their scalp for at least one week or longer 
prior to each study visit, as determined by the investigator based on visible scalp hair growth. 
Hair trimming outside the treatment areas to maintain the current hair style is permitted. 
10. Be willing and able to follow all study instructions and to attend all study visits. 
11. Subjects taking hormonal replacement therapies must be on stable doses for 6 months prior to 
enrollment and remain on the same maintenance dose throughout the study.  
12. Subjects taking thyroid replacement medication must be on stable doses for 6 months prior to 
enrollment and remain on the same maintenance dose throughout the study.  
13. 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. 
 
 
Double-Blind Exclusion Criteria 
Subjects are excluded from this study if any 1 or more of the following criteria is met: 
1. Females who are nursing, pregnant, or planning to become pregnant for the duration of the 
study and up to 30 days after the last application of study medication. 
2. Diffuse alopecia areata. 
3. Concomitant hair loss disorder (by history or physical exam) such as androgenetic alopecia, 
or scarring alopecia (e.g., cicatricial alopecia, frontal fibrosing alopecia, etc.).  Subjects 
without prior known history of androgenic alopecia (AGA) or other patterned hair loss 
disorder, who exhibit AGA or other patterned hair loss with regrowth during the study, will 
be allowed to continue in the study. 
4. Active skin disease on the scalp (such as psoriasis or seborrheic dermatitis) or a history of 
skin disease on the scalp that in the opinion of the investigator would interfere with the study 
assessments of efficacy or safety. 
5. Active scalp trauma or other condition affecting the scalp that, in the investigator’s opinion, 
may affect the course of AA or interfere with the study conduct or evaluations. 
6. The presence of a permanent or difficult to remove hairpiece or wig that will, in the opinion of 
the investigator, interfere with study assessments if not removed at each visit.   
7. History of, or current, severe, progressive or uncontrolled renal, hepatic, gastrointestinal, 
pulmonary, cardiovascular, genitourinary (renal disease) or hematological disease, 
neurologic or cerebral disorders, infectious disease or coagulation disorders that, as 
determined by the Investigator, would preclude participation in and completion of study 
assessments. 
8. History of, current or suspected systemic or cutaneous malignancy and /or 
lymphoproliferative disease, other than subjects with: a history of adequately treated and well 
healed and completely cleared non-melanoma skin cancers (basal or squamous cell 
carcinoma) treated successfully at least 1 year prior to study entry with no evidence of 
disease.   
9. Evidence of active or latent bacterial (including tuberculosis) or viral infections at the time of 
enrollment or history of incompletely treated or untreated tuberculosis.  Subjects who have 
completed therapy for latent tuberculosis may participate. 


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10. History of a serious local infection (e.g., cellulitis, abscess) or systemic infection including 
but not limited to a history of treated infection (e.g., pneumonia, septicemia) within 3 months 
prior to Baseline (Visit 2). Subjects on an antibiotic for a nonserious, acute local infection 
must complete the course prior to enrollment into the study. 
11. Positive for HIV, Hepatitis B or C.  Subjects with serologic evidence of Hepatitis B 
vaccination (Hep B surface Ab without the presence of Hep B sAg) will be allowed to 
participate. 
12. Herpes zoster or cytomegalovirus (CMV) that resolved less than 2 months before study 
enrollment. Subjects with a history of frequent outbreaks of Herpes Simplex Virus (defined 
as 4 or more outbreaks a year). 
13. Clinically significant laboratory abnormalities at screening that, in the opinion of the 
Investigator, would make the subject a poor candidate for the study.  
14. Subjects with absolute neutrophil count <1,800/mL or platelet count <130,000/mL.  
15. Subject unable to comply with the following required washout periods: 
 
Therapy/Medication 
Washout Period 
Systemic Therapies 
Disease Modifying Anti-Rheumatic Drugs 
(DMARDS), Biologics or immunosuppressants, such 
as: anakinra, adalimumab, azathioprine, 
corticosteroids, cyclosporine, etanercept, infliximab, 
methotrexate, TNF inhibitors, ustekinumab 
1 month or 5 half-lives whichever is greater 
Plaquenil 
2 months 
 
JAK inhibitors (oral or topical) 
6 months 
Intralesional Steroids (Scalp) 
1 month 
 
Topical Treatments on the Scalp 
 
Anthralin, bimatoprost, corticosteroids, 
diphencyprone, diphenylcycloprophenone (DPCP), 
Squaric acid dibutylester (SADBE), minoxidil, 
pimecrolimus, tacrolimus 
1 month 
Phototherapy, Laser Therapy, Excimer Laser 
3 months 
 
16. Participation 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) of Screening (Visit 1). Subjects who have participated in a study of an investigational 
drug, device or biologic agent for alopecia areata within 1 year of screening will be eligible 
to participate only with individual permission from the Medical Monitor. 
17. Sensitivity to any of the ingredients in the study medications. 
18. History of or current alcohol or drug abuse within 2 years of assessment for study enrollment. 
19. Unwillingness to refrain from weaves, hair extensions, or shaving of the scalp for at least one 
week or longer prior to each study visit, as determined by the investigator based on visible 
scalp hair growth the duration of the study. 


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20. Screening ECG findings of: 
• QTcF >450msec for males or >470msec for females (use of the ECG algorithm is 
acceptable for this purpose) 
• Clinically significant Heart rate < 45 or Heart Rate > 100 beats/minute 
• 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. 
 
Open-Label Extension 
At Week 24 (Visit 10) or Week 28 (Visit 11), the subject may be given the option to move into the 
OLE treatment if the subject meets the OLE entry criteria in Section 5.5.1. 
• 
If the subject declines the OLE, Visit 11 (Post-treatment) will be the last double-blind study 
visit.  
• 
If the subject chooses to continue into the OLE, she/he must sign an OLE ICF/Assent, 
complete Visit 10 or Visit 11, as appropriate, and OLE Visit 1, prior to being dispensed 
open-label drug and receiving continued study medication application instructions. The 
subject will be scheduled for OLE Visit 2.   
• 
If the subject enrolls in open-label treatment within 30 days of completion of Week 24 
(Visit 10) or Week 28 (Visit 11), OLE Visit 1 will be conducted to obtain consent/assent 
and perform the procedures in the Schedule of Assessments. This will be considered the 
official date that the subject initiated OLE treatment.  
• If the subject enrolls in open-label treatment > 30 days after completion of Week 28, OLE 
Visit 1 will be conducted in order to obtain consent/ assent, and complete the procedures 
detailed in the Scheduled of Events. This will be considered the official date that the subject 
initiated OLE treatment and the scheduling of subsequent visits will be based on this date. 
 
5.5.1. 
OLE Entry Criteria 
1. Subject must be able to comprehend and willing to sign the OLE Informed Consent/Assent 
Form (ICF). 
2. Subject must continue to meet the entry criteria from the double-blind period.  The SALT 
score and duration of disease are based on the double-blind period baseline visit. 
3. Subject has not experienced any clinically significant AEs, SAEs or tolerability issues that 
met the study discontinuation criteria in the double-blind period. 
4. Subject is capable of regrowing scalp hair in the opinion of the investigator. 
5. WOCBP must have a negative UPT at entry into OLE. 
 
 
Previous and Concomitant Medications and Therapies 
At Screening (Visit 1), the Investigator or designee will question the subject to ensure they have 
not used any excluded therapies (Section 5.6.2). 


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5.6.1. 
Permitted Concomitant Medications and Over the Counter Products (OTC) 
 
Concomitant therapies are any new or existing therapies received from Screening (Visit 1) until 
Week 28 (Visit 11).  Concomitant therapies include drug (e.g. prescription and over the counter 
[OTC]), and non-drug (e.g., chiropractic, physical therapy, energy-based treatments).  
Subjects will be allowed to take medications not restricted by the protocol as long as 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 hair and scalp products (shampoos, conditioners, styling products) should be reviewed by 
the Investigator and are permitted if, in the Investigator’s opinion, they will not affect the safety 
or efficacy of the subject during the study. Use of hair dyes is permitted during the study if the 
subject uses the same hair dye throughout the study.  If in the opinion of the Investigator, the hair 
dye interferes with study assessments the subject may be directed to wait until after the study visit 
to dye his or her hair.  Efforts should be made to keep the hair care regimen the same throughout 
the duration of the study. 
Topical therapies such as topical corticosteroids are permitted if they are not applied on or near 
the scalp. Inhaled or intranasal corticosteroids are allowed in the study. 
 
Prior permitted concomitant medications taken within 30 days of beginning treatment with 
ATI-50002 Topical Solution will be documented in the subject’s source document and eCRF.  In 
addition, any new permitted medications administered during protocol treatment and through end 
of study (Week 28 (Visit 11) or OLE Visit 6) will be documented in the subject’s source document 
and eCRF.   
 
5.6.2. 
Prohibited and/ or Restricted Medications 
Any medication, shampoo or hair product known to affect hair growth in AA is prohibited 
throughout the study period.  Subjects who are on a chronic stable dose of finasteride for benign 
prostatic hypertrophy for greater than 1 year are eligible for enrollment in the study as long as they 
maintain the same stable dose throughout the study.  Since subjects with known AGA are excluded 
from the study, treatment with finasteride for alopecia during the study or within one year prior to 
study enrollment is prohibited.  A list of medications and therapies that require a specific washout 
period prior to study entry and are not permitted during the study is in Table 1.   
 
Table 1:  Prohibited Medications 
Therapy/Medication 
Washout Period 
Systemic Therapies 
Disease Modifying Anti-Rheumatic Drugs 
(DMARDS), Biologics or immunosuppressants, 
such as: anakinra, adalimumab, azathioprine, 
corticosteroids, cyclosporine, etanercept, infliximab, 
methotrexate, TNF inhibitors, ustekinumab 
1 month or 5 half-lives whichever is greater 
Plaquenil 
2 months 


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JAK inhibitors (oral or topical) 
6 months 
Intralesional Steroids on the Scalp 
1 month 
Topical Treatments on the Scalp 
 
Anthralin, bimatoprost, corticosteroids, 
diphencyprone, diphenylcycloprophenone (DPCP), 
Squaric acid dibutylester (SADBE), minoxidil, 
pimecrolimus, tacrolimus 
1 month 
Phototherapy, Laser Therapy, Excimer Laser 
3 months 
 
 
Subject Identifier (SI) 
The Investigator will assign a unique five-digit subject identifier (SI) to each subject at Screening 
(Visit 1).  
The SI format will be NN-NNN, using leading zeroes as appropriate, where: 
• The first 2 digits are the investigational center site number assigned by Aclaris 
• The final 3 digits are the subject number (SN), assigned in ascending numerical order by 
the Investigator or designee, without omitting or repeating any number, starting with 001.  
For example, the SI for the twenty-third subject that signs an informed consent/ assent form at site 
number 01 would be 01-023. The subject will be identified using the SI in all study documentation 
for the duration of the study. 
 
 
Replacement Subjects 
Subject enrollment will continue until approximately 120 subjects have been randomized.  
Subjects who are randomized and do not complete the study will not be replaced. 
 
 
Subject Withdrawal Criteria 
Subjects will be informed that they are free to withdraw from the study at any time and for any 
reason. The investigator may remove a subject from the study if, in the investigator's opinion, it is 
not in the best interest of the subject to continue the study. Examples of other reasons subjects may 
be discontinued from the study are: a change in compliance with an inclusion or exclusion 
criterion, occurrence of AEs, occurrence of pregnancy, use of a prohibited therapy or subject is 
unwilling or refuses to continue with the protocol defined study visits and/or subject withdraws 
consent/ assent (Refer to Section 9.2.4 for study medication discontinuation or termination 
criteria).  
 
In case of premature discontinuation from double-blind study participation, all efforts will be made 
to perform all Visit 10 (Week 24) assessments. For premature discontinuations occurring in the 
OLE, all efforts will be made to perform all OLE Visit 6 assessments.  The date the subject is 
withdrawn from the study and the reason for discontinuation must be recorded in the subject’s 
electronic case report forms (eCRFs). All withdrawn subjects with ongoing AEs will be followed 
until the event has resolved or stabilized, until the subject is referred to the care of a local health 
care professional, or until a determination of a cause unrelated to the study medication or study 
procedures is made. 


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Study Termination 
This study may be terminated prematurely in whole or in part due to a change in the benefit/risk 
profile for ATI-50002 Topical Solution such that continuation of the study would not be justified 
on medical or ethical grounds.  This determination may be made by the Study Investigators in 
conjunction with the Sponsor, or by IRB or the U.S. Food and Drug Administration (FDA).  The 
Sponsor may also elect to terminate the study if enrollment is sufficiently slow to prevent the 
completion of the study in an acceptable timeframe, or if ATI-50002 development is discontinued. 
If the study is terminated prematurely, the Sponsor will notify the Study Investigators and the 
FDA. The Investigator must promptly notify all enrolled subjects and the IRB of study termination. 
 
 
INVESTIGATIONAL PLAN 
 
Overall Study Design 
This Phase 2, multicenter, randomized study is designed to evaluate the safety, tolerability and 
efficacy of ATI-50002 Topical Solution in subjects with stable patchy alopecia areata (AA).  
Subjects will be required to have a clinical diagnosis of alopecia areata (AA) with at least 15% 
up to 95% total scalp hair loss for a duration of the current episode of scalp hair loss of a 
minimum of 6 months and a maximum of 12 years.  
 
During the screening period, subjects will be assessed for eligibility into the study.  Subjects will 
apply up to a maximum of 4 mLs of study medication to the entire scalp twice a day for up to 24 
weeks in the double-blind period. Subjects who continue onto the OLE will apply ATI-50002-
Topical Solution, 0.46% twice-daily for 24 weeks to the scalp and if applicable to eyebrow(s).  
Assessment of response to treatment will be performed at Week 4 (Visit 5), Week 8 (Visit 6), 
Week 12 (Visit 7), Week 16 (Visit 8), Week 20 (Visit 9), Week 24 (Visit 10), post-treatment 
Week 28 (Visit 11, if applicable), and OLE Visits 3-6.  Safety and tolerability will be evaluated 
at each study visit by assessment of adverse events and vital signs, and at select visits, ECGs and 
clinical laboratory tests. 
 
 
STUDY PROCEDURES 
The investigator, a designated and appropriately trained staff member, or the subject will 
perform the study assessments according to the schedule of assessments (Section 6.3). The same 
staff member should perform the assessments for a given subject throughout the study. If this 
becomes impossible, an appropriate designee with overlapping experience with the subject and 
study should perform the assessments. The same lighting conditions and subject positioning 
should be used for all evaluations for a given subject. 
 


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Schedule of Assessments 
Double-Blind Period 
Screening 
Baseline 
Treatment 
Post-
Treatment 
Visit 1 
Visit 2 
 
Visit 
3 
Visit 
4 
 
Visit 
5 
 
Visit 
6 
 
Visit 
7 
 
Visit 
8 
Visit 
9 
 
Visit 
1014 
Visit  
1114 
 
Week 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
Treatment Day 
-30 to 0 
1 
8 
15 
29 
57 
85 
113 
141 
169 
197 
Treatment Window(days) 
N/A 
N/A 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Informed consent/ assent1 
X 
 
 
 
 
 
 
 
 
X14 
X14 
Inclusion/exclusion criteria  
X 
X 
 
 
 
 
 
 
 
 
 
Physical exam2 
X 
 
 
 
 
 
 
 
 
X 
 
Demographics & medical history 
X 
 
 
 
 
 
 
 
 
 
 
Alopecia Areata History  
X 
 
 
 
 
 
 
 
 
 
 
Vital signs3  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical CBC, Chemistry, Virology, Serum Pregnancy, 
Urinalysis4 
X4 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test5 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
ECG  
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
SALT Score (prior to ALODEX)6 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
ALODEX Score (after SALT)7 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Target Scalp Patch Identification8 
 
X 
 
 
 
 
 
 
 
 
 
Assessment of hair quality9 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Alopecia Appearance Assessment (AAA): Clinician Rating (CR)  
All Patches, Target Patch10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Alopecia Appearance Assessment (AAA): Subject Rating (SR)  
All Patches, Target Patch10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Physician Global Impression of Severity (PhGIS)10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Physician Global Impression of Change (PhGIC) 
 
 
 
 
 
 
 
 
 
X 
 
Subject Global Impression of Severity (SGIS) 10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Subject Global Impression of Change (SGIC) 
 
 
 
 
 
 
 
 
 
X 
 
Subject Global Impression Treatment Satisfaction (SGITS) 
 
 
 
 
 
 
X 
 
 
X 
 
DLQI10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Alopecia Impact Assessment (AIA):  Subject Rating10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Photography (complete scalp and target patch) 10 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Subject randomization 
 
X 
 
 
 
 
 
 
 
 
 
Subject instructions11  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Dispense, collect, weigh study medication, assess compliance 12  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
In office study medication application13 
 
X 
 
 
 
 
 
 
 
 
 
Concomitant therapies 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol: ATI-50002-AA-201 
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Version 9.0, Date: 09APR2019 
Double-Blind Period 
Screening 
Baseline 
Treatment 
Post-
Treatment 
Visit 1 
Visit 2 
 
Visit 
3 
Visit 
4 
 
Visit 
5 
 
Visit 
6 
 
Visit 
7 
 
Visit 
8 
Visit 
9 
 
Visit 
1014 
Visit  
1114 
 
Week 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
Treatment Day 
-30 to 0 
1 
8 
15 
29 
57 
85 
113 
141 
169 
197 
Treatment Window(days) 
N/A 
N/A 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Select Sites Only16 
4 mm Punch biopsy17 
 
X 
 
 
X 
 
 
 
 
X 
 
Suture removal, if applicable18 
(Approximately 2-weeks after punch biopsy) 
 
 
 
X 
X16 
 
 
 
 
X16 
 
Blood for immunologic studies19 
 
X 
 
 
X 
 
 
 
 
X 
 
Schedule Telephone Call to occur the Day Prior to Visit 5, and 
Visit 1020 
 
 
 
X 
 
 
 
 
X 
 
 


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1A written, signed ICF/ assent must be obtained from each subject prior to performing any study related procedure (i.e., prior to performing vital signs, standardized photography, 
biopsies, clinical laboratory sampling or urine pregnancy tests.)  An OLE ICF must be obtained prior to performing any OLE assessments. 
2 A physical exam includes: general appearance, extremities, examination of head, eyes, ears, nose and throat, respiratory, cardiovascular, abdominal, neurological, musculoskeletal, 
lymphatic and skin assessment. 
3Vitals signs include: oral or ear temperature, blood pressure, heart rate, respiration rate (height and weight at baseline only). 
4 Clinical laboratory sampling include: CBC, Chemistry with lipids, Urinalysis.  Quantiferon Gold, HIV, Hepatitis B and C, and Serum Pregnancy should be done at screening visit 
only. 
Open-Label Extension 
Open-Label Treatment 
Post-Treatment 
OLE Visit 1 
OLE 
Visit 2 
 
OLE 
Visit 3 
OLE 
Visit 4 
 
OLE 
Visit 5 
OLE 
Visit 6 
 
Week 
OLE Visit 1 
occurs at Visit 
10 or 11 
Visit 11 (Week28) 
was: 
2 
4 
12 
24 
28 
Treatment Day 
≤ 30 
Days 
> 30 Days 
15 
29 
85 
169 
197 
Treatment Window(days) 
NA 
NA 
NA 
± 3 
± 3 
± 7 
± 7 
± 7 
Informed Consent/ Assent 
X 
X 
X 
 
 
 
 
 
Inclusion/exclusion criteria  
X 
X 
X 
 
 
 
 
 
Physical exam2 
 
 
X 
 
 
 
 
X 
Medical History Update 
 
 
X 
 
 
 
 
 
Vital signs3  
 
X 
X 
X 
X 
X 
X 
X 
Clinical CBC, Chemistry, Virology, Serum Pregnancy, 
Urinalysis4 
 
 
X 
X 
X 
X 
X 
X 
Urine pregnancy test5 
 
X 
X 
X 
X 
X 
X 
X 
ECG  
 
 
 
 
 
 
 
X 
SALT Score (prior to ALODEX)6 
 
X15 
X 
 
X 
X 
X 
X 
ALODEX Score (after SALT)7 
 
X15 
X 
 
X 
X 
X 
X 
Alopecia Appearance Assessment (AAA): Clinician 
Rating (CR)  
All Patches, Target Patch 
 
 
 
 
X 
X 
X 
Alopecia Appearance Assessment (AAA): Subject 
Rating (SR)  
All Patches, Target Patch 
 
 
 
 
X 
X 
X 
Subject Global Impression Treatment Satisfaction 
(SGITS) 
 
 
 
 
 
X 
 
Photography (complete scalp and target patch)  
 
   X15 
 
X 
X 
X 
X 
Subject instructions11  
X 
X 
X 
X 
X 
X 
 
Dispense and weigh study medication12  
X 
X 
X 
X 
X 
X 
(Weigh only) 
 
Collect study medication, assess compliance 
 
 
X 
X 
X 
X 
 
Concomitant therapies 
 
X 
X 
X 
X 
X 
X 
Adverse events  
 
X 
X 
X 
X 
X 
X 


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Page 37 of 82 
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5 UPT must be performed in WOCBP prior to randomization at Baseline (Visit 2) and must be negative for the subject to continue in the study.  UPTs in WOCBP must also be obtained 
at Visits 5, 6, 7, 8, 9, 10, 11 and if applicable, OLE Visit 1, and OLE Visit 2-6.  WOCBP must have a negative serum pregnancy test at Screening (Visit 1) and a negative UPT at 
baseline (Visit 2) prior to randomization. WOCBP must have a negative UPT prior to continuation into the OLE. 
6 SALT score must be determined prior to ALODEX using device provided.  At Baseline (Visit 2), SALT score should be determined prior to application of study medication. 
7 ALODEX score determined after SALT score using device provided. At Baseline (Visit 2), ALODEX score should be determined prior to application of study medication. 
8 The subject will be instructed to identify the most bothersome patchy area- this will be the Target Patch. At Baseline (Visit 2), the Target Patch should be identified prior to application 
of study medication. 
9 The investigator will assess active hair loss through the hair pull test and the presence of exclamation point hairs.  At Baseline (Visit 2), the assessment should be determined prior to 
application of study medication. 
10 At Baseline (Visit 2), study assessments must be performed prior to application of study medication. 
11 The study staff must instruct the subject to apply study medication according to the instructions in APPENDIX 1, 2 and 3. 
12 The study staff must weigh the study medication bottle(s) with cap prior to dispensing to the subject and after the study medication bottles are returned to the investigational site.  
Staff should review the usage based on the weight of the bottle and counsel the subject as necessary. 
13 At Baseline (Visit 2), the first application of study medication should be performed by the subject under the supervision of the study staff and the subject should be observed for 20 
minutes after the initial application. 
14At Week 24 (Visit 10) or Week 28 (Visit 11), the subject may be given the option to move into the OLE treatment. 
• 
If the subject declines the OLE, Visit 11 (Post-treatment) will be the last double-blind study visit.  
• 
If the subject chooses to continue into the OLE, she/he must sign an OLE ICF, complete Visit 10 or Visit 11 as appropriate and OLE Visit 1, prior to being dispensed open-
label drug and receiving study medication application instructions. The subject will be scheduled for OLE Visit 2.   
• 
If the subject enrolls in open-label treatment within 30 days of completion of Week 24 (Visit 10) or Week 28 (Visit 11), OLE Visit 1 will be conducted to obtain consent/assent 
and perform the procedures in the Schedule of Assessments. This will be considered the official date that the subject initiated OLE treatment.  
• 
If the subject enrolls in open-label treatment > 30 days after completion of Week 28, OLE Visit 1 will be conducted to obtain consent/ assent, and complete the procedures 
detailed in the Scheduled of Events. This will be considered the official date that the subject initiated OLE treatment and the scheduling of subsequent visits will be based on 
this date.  
15 SALT, ALODEX and Photography is performed at OLE Visit 1 (if Week 28 is < 30 days) only if there is a significant change from the last double-blind study visit. 
Select Sites Only16 
16 At Baseline (Visit 2) the scalp biopsy and blood samples for immunologic evaluations must be performed prior to study medication application. At Week 4 (Visit 5), and Week 24 
(Visit 10), the scalp biopsy and blood samples for immunologic evaluations must be performed prior to study medication application.  The evening prior to the Week 4 (Visit 5), and 
Week 24 (Visit 10) visits, the subject should be instructed to apply study medication approximately 12 hours prior to Week 4 (Visit 5), and Week 24 (Visit 10) visit time and to note 
the time of application.  Subjects should be instructed not to apply study medication before the Week 4 (Visit 5), and Week 24 (Visit 10) visits. 
17 The biopsy will be performed by the investigator or designee using a 4mm punch biopsy per instructions in APPENDIX 11. The Baseline/Day 1 (Visit 2) biopsy must be obtained 
prior to the first application of study medication. Subjects must be instructed not to apply study medication to the biopsy site until instructed to by the investigator or designee. Study 
assessments including photography should be completed prior to the biopsy. (Select sites only)  
18 Sutures will be removed approximately 2 weeks following biopsy unless absorbable sutures are used precluding the need for suture removal. (Select sites only) 
19 Blood samples for immunologic studies will be obtained prior to study medication application on Baseline (Day 1/ Visit 2), Week 4 (Visit 5), and Week 24 (Visit 10).  (Select sites 
only) 
20 A member of the study staff should schedule a reminder call with the subject to occur on the day before Week 4 (Visit 5), Week 8 (Visit 7), and Week 24 (Visit 10) to remind the 
subject to apply the study medication approximately 12 hours prior to the visit and to hold the morning dose of study medication.  The subject should be instructed to document the 
time of application and quantity of the dose applied.  


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Duration of the Study 
Double-blind Period 
The anticipated time for study enrollment is 6 months.  The duration of the screening period could 
be up to 30 days.  Once randomized, the maximum duration of double-blind study treatment from 
Baseline (Visit 2) to the post-treatment follow-up visit at Week 28 (Visit 11) is anticipated to be a 
maximum of 200 days (197 days + 3-day window). 
 
Open-Label Extension 
The maximum duration of the of study treatment in the OLE is 176 days (168 days + 7-day 
window).  The maximum duration of the study participation from entry into the OLE to completion 
of the post-treatment follow up visit is 204 days.   
 
 
STUDY TREATMENT 
 
Investigational Study Medication 
The study medications for this study are ATI-50002 Topical Solution in dosage strengths of 0.46% 
and 0.12% and Vehicle Topical Solution. The study medications are formulated as thin clear 
solutions that are indistinguishable as packaged and labelled.  The inactive ingredients include: 
water, transcutol P, propylene glycol, PEG400, dimethyl sulfoxide (DMSO), kolliphor CS 20, 
benzyl alcohol, poloxamer 188, and povidone K30. 
 
STUDY MEDICATION INFORMATION 
Study medication 
name 
Double-Blind Period 
Open-Label Period 
ATI-50002 
ATI-50002 
Vehicle 
ATI-50002 
Dosage Strength 
0.46% 
0.12% 
- 
0.46% 
Manufacturer 
PMRS, Inc., Horsham, PA 
Pharmaceutical 
Form 
Topical Solution 
Container 
Amber Glass Bottle, 120 mL with screw cap  
Storage Conditions 
59°F to 77°F (15°C to 25°C)  
Dose regimen 
Route 
Topical 
Frequency 
Twice-daily 
Duration of 
administration 
24 weeks 
24 Weeks 
Other supplies 
Disposable, single-use droppers will be provided. 
 
 
Subject Randomization 
Prior to the start of the study, Aclaris Therapeutics, Inc. or a designated third party will generate a 
list of randomization numbers that shall be transmitted to the assigned clinical packaging 
organization for study medication labeling.  The randomization list will be stored with access 
limited to designated personnel for study medication labeling.  The randomization list will be made 
available, as appropriate, to unblind the database.   
 


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In the double-blind period, subjects will be assigned to 1 of the 3 treatment groups in a random 
manner and at a 1:1:1 ratio. At Baseline (Visit 2), an investigational center staff member will assign 
study medication to eligible subjects by selecting an appropriate Subject Kit.  The staff member 
must select Subject Kits in chronological sequence and in an ascending numerical order starting 
with the lowest available Subject Kit number.  No Subject Kit number may be omitted or reused.  
The Subject Kit number is the randomization number.   
 
The investigational staff member randomizing the subject will enter the subject identifier, subject 
initials, and date randomized on both parts of the Subject Kit label, remove the tear-off part, attach 
it to the subject’s study medication eCRF label page and record the Subject Kit number in the 
subject’s eCRF. 
 
In the open-label period, all subjects will receive the dosage strength of 0.46%.  
 
 
Application of Study Medication 
For participants < 18 years of age, the parent and study staff should assess the subject’s ability to 
apply study medication to the scalp for the duration of the study.  For subjects who are not able to 
apply study medication to their scalp, a parent will apply the study medication using gloves.  
Subjects or their parents will be instructed to apply a thin film of ATI-50002 Topical Solution or 
matching vehicle up to 4-mLs, twice-daily; once in the morning and approximately 12 hours later 
to the entire scalp following the instructions in APPENDIX 1.  The subject or parent must wash 
her/his hands thoroughly before and after each study drug application. At each study visit, subjects 
should bring the study medication including unused bottles back to the site.  The disposable 
droppers should be disposed of at the subject’s home. 
 
Following review of study medication instructions, subjects or their parents will apply the first 
dose of study medication in the office under the instruction and supervision of the study staff.   
During the Baseline visit (Visit 2), the study staff member will: 
• Dispense the appropriate study medication bottle. 
• Weigh the bottle with the cap prior to the first study medication application. 
• Instruct the subject on the appropriate application technique following instructions in 
APPENDIX 1. 
• For select sites only:  Instruct the subject not to apply study medication to the biopsy site. 
• Observe the subject’s first study medication application to ensure proper coverage and 
monitor the subject for at least 20 minutes after application.   
• Record the quantity in mLs of study medication the subject applied to cover the entire scalp 
in the source document, eCRF and on the subject instruction sheet. 
• After the first application, the study staff should weigh the study bottle with the cap.   
• Provide feedback on the application procedure, if needed.  
 
In the OLE, in addition to applying study medication to the entire scalp twice-daily (or 
patchy areas with a ½” margin if the subject did not agree to apply to the entire scalp) 
subjects with eyebrow loss will be allowed to apply a thin film of study medication twice-
daily to the affected eyebrow(s) as detailed in APPENDIX 3.  Subjects should be instructed 
to apply the study medication to the entire natural eyebrow(s) and not just the patches. 


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Version 9.0, Date: 09APR2019 
7.3.1. 
Subjects Who Signed Consent Prior to Amendment 5 
Subjects who signed the ICF prior to amendment 5 and do not consent to twice-daily 
applications to the entire scalp may continue in the study.  These subjects should be given the 
option to apply the study medication to the entire scalp at night only, and the patchy areas 
during the day or to the patchy alopecia areas and a ½” margin around the areas twice-daily.  
The areas being treated must be identified in the source documentation and the eCRF as: 
• patchy areas only twice-daily,  
• entire scalp twice-daily or  
• patchy areas only once-daily, and entire scalp once-daily. 
 
 If the subject develops a new patch of hair loss during the study (e.g. areas of the scalp with active 
shedding) the investigator will instruct the subject to treat the new area of hair loss.  The 
investigator must incorporate the new area of hair loss, once it is clinically evident, into the SALT 
and ALODEX score assessments.  The investigator must determine if additional study medication 
is required to cover the new patchy area(s) and if applicable, document the new amount of study 
medication to be applied in the source documents and on the subject instruction sheet.  If a subject 
believes symptoms indicate a new area of impending hair loss, but no hair loss is clinically 
apparent, the area will be noted in the source document, but will not be treated or included in SALT 
or ALODEX assessment until clinically apparent as either thinned or alopecic patch.  New patches 
of hair loss that develop during the study are not considered an adverse event. 
 
 
Study Medication Weights 
A study staff member will weigh the study medication bottles with the cap prior to dispensing to 
the subject and after collection of the study medication bottles during study treatment visits.  
Bottles that are not dispensed to the subject do not need to be weighed. 
 
Treatment Compliance 
The investigator or designee will be responsible for monitoring subject compliance through 
questioning the subject, documenting missed doses, if any, weighing the bottle before dispensing 
and after return and visual inspection of the quantity in the study medication bottles (used and 
unused).  Study staff will counsel the subjects, as required to make sure subjects are compliant 
with study medication applications. 
 
 
Dose Modification  
If the subject experiences application site AE(s), study medication may be stopped for up to a total 
of 3 days or the frequency of study medication application may be reduced from twice-daily to 
once-daily for up to a total of 6 days.  Dose modifications greater than these must be reviewed 
with the Medical Monitor. Refer to Section 9.2.4 for Study Medication Interruption or 
Discontinuation due to related SAEs or specific abnormal laboratory values.   
 


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Study Medication Accountability 
The Principal Investigator or designee is responsible for ensuring accountability for the 
investigational agent, including reconciliation of medications and maintenance of medication 
records.  Upon receipt of study medication, the clinical site will check for accurate delivery and 
acknowledge receipt by signing (or initialing) and dating the documentation provided.  One copy 
of this document will be returned to Aclaris Therapeutics, Inc. (or designee) and one copy will be 
maintained in the study file. In addition, an accurate study medication disposition record will be 
kept, specifying the amount dispensed for each subject and the date of dispensing. This inventory 
record will be available for inspection at any time. At the completion of the study, the original 
inventory record will be available for review by Aclaris Therapeutics, Inc. upon request.  Final 
medication accountability will be performed by the study monitor at the completion of the study 
and all used and unused study medication bottles will be returned to Aclaris Therapeutics, Inc. or 
designee for disposal.  
 
 
Other Study Supplies 
Aclaris Therapeutics, Inc. or a third party vendor will provide: 
• Supplies and instructions for collecting, labeling, shipping and result reporting for the 
clinical laboratory tests and urine pregnancy tests. 
• A scale to weigh the study medication bottles. 
• Equipment, supplies and training for taking standardized photographs. 
• An iPad for recording the SALT and ALODEX score. 
• Hair clips and Insulated lunch bags. 
• Equipment, supplies and training for performing standardized ECGs. 
• Select sites only:  Supplies and instructions for collecting the scalp biopsies and blood tests. 
• Gloves 
 
 
Blinding 
Blinding of study medication is important for validity of this study.  This double-blind period of 
the study uses a double-blind design.  The study medications are indistinguishable in appearance, 
as packaged and labeled.  
7.9.1. 
Unblinding the Study Medication 
During the double-blind period, the blinding may be broken ONLY in the event of a medical 
emergency, in which knowledge of the study medication identity is critical to the management of 
the subject’s course of treatment.  Before breaking the blind, the investigator shall determine that 
the information is necessary (i.e., that is, will alter the subject’s immediate course of treatment).  
In many cases, particularly when the emergency is clearly not study medication-related, the 
problem may be effectively managed by assuming that the subject is receiving an active study 
medication without the need for unblinding.   
 
If the investigator deems it necessary to break the blind for a study subject, he/she will attempt to 
contact the Medical Monitor (protocol page 1) to obtain permission.  If it is not possible to contact 
the Medical Monitor beforehand, contact her/him as soon as possible after breaking the blind for 
a subject.   


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Page 42 of 82 
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To identify a subject’s study medication, locate the second panel of the tear-off label from the 
Subject Kit attached to the subject’s study medication label page and follow the instructions on the 
label.  Record the date of unblinding, the reason for unblinding, and the initials of the 
investigational staff member who performed the unblinding on the subject’s study medication label 
page.  Any subject whose blind has been broken must be discontinued from the study (Section 5.9). 
 
At the end of the study, the original study medication label pages will be returned to Aclaris 
Therapeutics, Inc. with a photocopy placed in the investigator’s study file.  The original study 
medication label pages will be available, upon request, to the site if needed to respond to a 
regulatory audit. 
 
 
Study Medication Packaging, Labeling, Storage and Security 
The study medication must be used by the study subjects only.  Investigational site staff will 
explain the application of the study medication to subjects.   
 
Study medication will be provided by Aclaris Therapeutics, Inc. and labeled according to 
regulations.  Study medications must be stored in a secure area with limited access under 
appropriately controlled and monitored storage conditions.  Study medication should be stored at 
controlled room temperature 59°F - 77°F (15°C – 25°C).  Subjects will be instructed to store the 
study medication in the original glass bottle (in the carton provided) at room temperature, away 
from heat, moisture, direct light, and to keep it from freezing and out of the reach of children. 
 
The study medication will be supplied in amber glass 120 mL bottles.  Disposable droppers with 
1 mL calibration mark will be provided in the study kits.   
 
For the double-blind period, two Subject Kit boxes will be provided.  Each Subject Kit box will 
contain 15 bottles in individual boxes and disposable droppers.  Each kit will be labelled with a 
two-part, three panel, double blind label.  One part (one-panel) of the label remains attached to the 
Subject Kit, the other part (two-panel tear-off) is separated and attached to the subject’s study 
medication eCRF label page when the subject is randomized.  Each box and bottle will be labeled 
with a single panel label.   
 
For the open-label period, subjects will receive approximately 1-3 bottles of ATI-50002-Topical 
Solution, 0.46% per month.  Each bottle is numbered and packaged in a carton and both the bottle 
and carton will be labelled with a single-panel label. 
 
STUDY ASSESSMENTS 
Note that all subject evaluations (Alopecia Appearance Assessment, Global Impression of Severity 
and questionnaires) should be performed prior to any investigator assessments.  However, the 
investigator may assist in determining the location of the target patch prior to subject assessments. 
 


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Page 43 of 82 
Version 9.0, Date: 09APR2019 
 
Assessments of Efficacy 
8.1.1. 
Severity Alopecia Tool (SALT) Score 
The SALT score is a measurement of the amount of scalp without any terminal hair. The 
investigator will assess the SALT score using an iPad provided by Aclaris at baseline and monthly 
during the study. The SALT score must be determined prior to the ALODEX score.  At the baseline 
visit (Visit 2), the SALT score must be determined prior to randomization and the score must be 
at least 15% to 95% total scalp hair loss.  Equipment, supplies, training and the detailed Reference 
Guide will be provided to the investigational site prior to the initiation of subject enrollment. 
 
8.1.2. 
Alopecia Density and Extent Score (ALODEX) 
The ALODEX score is a measurement of the amount of scalp with terminal hair loss.  The 
investigator will calculate the ALODEX score using the iPad provided by Aclaris at baseline and 
monthly during the study.  The ALODEX score must be determined after the SALT score.  At the 
baseline visit (Visit 2), the ALODEX score must be determined prior to randomization.  
Equipment, supplies, training and the detailed Reference Guide will be provided to the 
investigational site prior to the initiation of subject enrollment. 
 
8.1.3. 
Alopecia Target Scalp Patch Identification 
At the baseline visit (Visit 2), the investigator will ask the subject to identify the most bothersome 
scalp patchy area, which will be identified as the target patch.  The target patch must be assessed 
by the subject as “no hair” or “a little hair” at Baseline (Visit 2). In subjects with extensive hair 
loss, the target patch may be a large scalp surface area. The target scalp patch must be identified 
prior to study medication application.  The target patch will be documented photographically at 
baseline and monthly throughout the study. Equipment, supplies, training and the detailed 
Reference Guide will be provided to the investigational site prior to the initiation of subject 
enrollment. 
 
8.1.4. 
Alopecia Appearance Assessment (AAA) for Patchy AA: Clinician and Subject 
The appearance of the subject’s patchy AA for both the target scalp patch and all affected patchy 
areas on the scalp will be assessed using the AAA by both the investigator and the subject at 
baseline (prior to study medication application) and at Day 29 (Visit 5), Day 85 (Visit 7),  Day 169 
(Visit 10), and OLE Visits 4-6 during study treatment.  At the baseline visit, both the Clinician’s 
and the Subject’s AAA should be assessed as “no hair” or “a little hair”.  The Clinician’s AAA is 
below and the Subject’s AAA is in APPENDIX 6. 
 
 
Alopecia Scalp Appearance Assessment for AA Patchy: Clinician Rating (CR) 
 
Instructions for item 1: Please mark an “X” in the box (☒) that best describes the appearance 
of the subject’s target patch right now.  Please select the one response that best represents your 
answer. 
Full hair, scalp of the target patch completely covered with hair 
Most hair, scalp of the target patch mostly covered with hair 


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Some hair, scalp of the target patch somewhat covered with hair 
A little hair, scalp of the target patch mostly exposed 
No hair, scalp of the target patch completely exposed 
 
Instructions for item 2: Please mark an “X” in the box (☒) that best describes the appearance 
of the subject’s whole scalp right now.  Please select the one response that best represents your 
answer. 
Full hair, whole scalp completely covered with hair 
Most hair, whole scalp mostly covered with hair 
Some hair, whole scalp somewhat covered with hair 
A little hair, whole scalp mostly exposed 
No hair, whole scalp completely exposed 
 
8.1.5. 
Global Impression of Severity 
The severity of the subject’s patchy AA will be assessed at baseline (Visit 2) (prior to study 
medication application) and at Week 4 (Visit 5), Week 12 (Visit 7), and Week 24 (Visit 10) during 
study treatment by both the investigator and the subject using the Global Impression of Severity 
Questionnaires.  The Physician’s scale is below and the subject’s scale is in APPENDIX 7. 
 
PHYSICIAN GLOBAL IMPRESSION OF SEVERITY (PhGIS) 
Please mark an “X” in the box (
) that best describes the severity of the patient’s patchy 
alopecia areata right now. 
Overall, how severe is the patient’s patchy alopecia areata right now? 
☐ Mild 
☐ Moderate 
☐ Severe 
☐ Very Severe 
☐ Extremely Severe 
 
8.1.6. 
Global Impression of Change 
The investigator will assess their overall impression of change for the subject’s alopecia at Week 
24 (Visit 10) using the 7-point Physician Global Impression of Change (PhGIC) detailed below. 
Compared to the subject's hair loss at Baseline [prior to study medication initiation], the subject's 
AA, AT or AU is (Please mark an “X” in the box (
):  
1=Very much improved since the initiation of treatment;  
2=Much improved;  
3=Minimally improved;  
4=No change from baseline (the initiation of treatment);  
5=Minimally worse;  
6= Much worse;  


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7=Very much worse since the initiation of treatment. 
 
The investigator or study staff will instruct subjects to answer the Subject Global Impression of 
Change (SGIC) questionnaire at their final study visit to report their overall impression of change 
for their condition. Subjects will assess change in the severity of their condition on a 7-point scale 
from Very much improved to Very much worse; the SGIC can be found in APPENDIX 12. 
 
8.1.7. 
Hair Quality Assessments 
Hair quality will be assessed by the investigator using the hair pull test including the presence of 
exclamation point hairs at baseline (prior to study medication application) and then monthly during 
the double-blind period study.   
 
8.1.7.1 
Hair Pull Test 
The hair pull test is performed at the edge of the alopecic patch as follows: 
• Pinch 25 to 50 hairs between non-gloved thumb and forefinger and exert slow, 
gentle traction while sliding fingers up. 
• Resulting extracted hairs should be examined with magnification and counted. 
 
Normal: 1 to 2 hairs dislodged 
 
Abnormal: > 2 hairs dislodged 
 
Broken hairs (structural disorder) 
 
Broken-off hair at the borders of an alopecic patch that are easily removable 
(in alopecia areata) 
 
 
Biomarker Assessment (Selected Sites only) 
Scalp biopsies and blood samples for immunologic evaluation will be obtained prior to study 
medication application at Baseline (Visit 2), Week 4 (Visit 5), and Week 24 (Visit 10).  The timing 
of the Week 4 (Visit 5), and Week 24 (Visit 10) samples should be approximately 12 hours after 
the previous evening study medication application.  The study staff should instruct the subject not 
to apply the study medication the morning of the Week 4 (Visit 5), and Week 24 (Visit 10) visits 
and to apply the study medication approximately 12 hours prior to the study visit. The subject 
should also be instructed to record the dose applied and the time. All study assessments (i.e. SALT 
and ALODEX score, AAA, PhGIS, SGIS, DLQI, AIA and photography) should be performed 
prior to the scalp biopsies. 
 


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8.2.1. 
Scalp Biopsy (Selected Sites Only) 
Scalp biopsies will be obtained at Baseline (Visit 2) before study medication application and at 
Week 4 (Visit 5), and Week 24 (Visit 10) 12 hours after the evening dose of study medication for 
histology and RNA sequencing (APPENDIX 11).  An additional unscheduled biopsy may be 
obtained with the subject’s consent/ assent based on the investigator’s assessment of worsening of 
alopecia or other clinically significant finding. The study staff should call the subject on the day 
prior to the Week 4 (Visit 5), and Week 24 (Visit 10) visits to instruct the subject to apply the 
study medication in the evening approximately 12 hours prior to the Week 4 (Visit 5), and Week 24 
(Visit 10) visits.  The subject should also be instructed to record the dose applied and the time. 
 
8.2.2. 
Blood for Immunologic Evaluation (T-cells) (Selected Sites Only) 
The blood samples for immunologic evaluation will be obtained at Baseline (Visit 2) and at Week 4 
(Visit 5), and Week 24 (Visit 10) for measurement of the following tests including: 
• T, B, NK lymphocytes, CD4+, CD8+ T-cells 
• T-regulatory and T-cell subtypes 
• RNA seq 
• TCR seq 
 
Assessment of Subject Satisfaction and Patchy AA Impact  
8.3.1. 
Subject Global Impression of Treatment Satisfaction 
The investigator or study staff will instruct the subject to answer this questionnaire in relation to 
their satisfaction with the outcome of the study medication response.  Subjects will assess their 
satisfaction with the outcome of the study treatment in all treated patchy areas on a 7-point 
satisfaction scale from extremely satisfied to extremely dissatisfied at Week 12 (Visit 7) Week 24 
(Visit 10), and if continuing in the open label extension, OLE Visit 5. 
 (APPENDIX 8). 
8.3.2. 
Alopecia Impact Assessment (AIA):  Subject Rating 
The Investigator or study staff will instruct the subject to answer the AIA questionnaire during the 
study visit at Baseline (Visit 2), Week 4 (Visit 5), Week 12 (Visit 7), and Week 24 (Visit 10) 
(APPENDIX 9). 
 
8.3.3. 
Dermatology Life Quality Index (DLQI) 
The impact of patchy AA on the quality of life of subject will be assessed using the DLQI 
(APPENDIX 10) at Baseline (Visit 2), Week 4 (Visit 5), Week 12 (Visit 7), and Week 24 
(Visit 10).  The investigator or study staff will instruct the subject to answer the questions based 
on the scalp hair loss instead of skin. 
 
 
Assessment of Safety 
Safety will be assessed throughout the study by the investigator or a designated and appropriately 
trained staff member. 
 


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8.4.1. 
Vital signs 
Vital signs will be measured at each visit during the study. The following items will be measured: 
• Body temperature, (oral or ear) 
• Pulse rate 
• Respiration rate 
• Blood pressure (systolic and diastolic) after the subject sits quietly for at least 5 minutes 
• Height (at Visit 2 only) 
• Weight (at Visit 2 only) 
 
Any measure that is, in the opinion of the investigator, abnormal AND clinically significant (CS) 
must be recorded as history if found prior to the first study medication application, or as an AE if 
found after the first study medication application begins.  
 
A systolic blood pressure >140mm Hg or a diastolic blood pressure >90 mmHg is considered 
abnormal and therefore must be defined as CS or not clinically significant (NCS) in the eCRF.  A 
weight >300 lbs. is considered abnormal and therefore must be defined as CS or NCS in the eCRF.  
 
8.4.2. 
Physical Examination 
The investigator or designee will perform a physical examination for all body systems (general 
appearance, extremities, examination of head, eyes, ears, nose and throat, respiratory, 
cardiovascular, abdominal, neurological, musculoskeletal, lymphatic and skin assessment) at 
Screening (Visit 1), end of study Week 24 (Visit 10) and if applicable, OLE Visit 1 and OLE Visit 
6. 
 
8.4.3. 
Clinical Laboratory Assessments 
A qualified staff member will collect non-fasting samples for clinical laboratory analysis at 
screening and baseline and then monthly throughout the study. Samples will be sent to ACM 
Global Laboratories for analysis.  Refer to the study specific laboratory manual for handling and 
shipping instructions. The following tests 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 
 


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Total bilirubin 
Urinalysis 
Total protein 
 
Uric acid 
Total cholesterol, LDL, HDL, 
Triglycerides 
Creatine Phosphokinase (CPK) 
Screening Only 
Virology (HepB, HCV, HIV) 
Quantiferon Gold 
Total Iron Binding Capacity (TIBC) 
Serum iron 
Serum Ferritin 
T3/T4, TSH 
Serum pregnancy 
 
 
The following clinical laboratory tests:  TIBC, serum iron, serum ferritin, T3/T4, TSH are drawn 
at screening to rule out any underlying conditions that could be causing alopecia. The results of 
the clinical laboratory tests will be reported on ACM Global Laboratory’s standard reports. The 
investigator must note NCS or CS to define the clinical relevance of any result that is outside the 
normal range for the laboratory. The investigator must date and initial every laboratory report.  
The investigator or subinvestigator must review all the Screening (Visit 1) laboratory test results 
against the study entry criteria for each subject prior to Baseline (Visit 2). The investigator must 
report all laboratory results that are BOTH outside the normal range for the laboratory AND, in 
the opinion of the investigator, CS as medical history if found prior to the first study medication 
treatment or as an AE if found after the first study medication treatment begins. Throughout the 
study, the investigator must review all laboratory reports in a timely manner. 
8.4.4. 
Pregnancy tests 
Subjects who are WOCBP must have a negative serum pregnancy test result at Screening (Visit 1) 
to continue in the study, and a negative UPT at Baseline (Visit 2) prior to randomization.  In 
addition, the investigator or designee will perform a urine pregnancy test for subjects who are 
WOCBP at monthly visits during the double-blind portion of the study and during the OLE at OLE 
Visit 1 (if Visit 28 > 30 days from entry to OLE), and OLE 2-6. The UPT kits provided by ACM 
Global Laboratories have a minimum sensitivity of 25-mIU ß-HCG/milliliter (mL) of urine. If the 
result of any post-treatment urine pregnancy test is positive, the subject will be withdrawn from 
the study and the subject’s pregnancy documented and followed. 
 
8.4.5. 
ECGs 
Standard 12-lead ECGs will be performed by a qualified staff member at Screening (Visit 1), 
Baseline (Visit 2), Day 15 (Visit 4) and monthly visits during the double-blind period study and if 
subject is continuing in the OLE, at OLE Visit 6.  The ECGs must be obtained using a standard 
12-lead ECG with a 10mm/mV amplitude, at 25mm/sec and a 5 to 10-second duration. To ensure 
a steady heart rate the subject must rest quietly in the supine position for at least 5 minutes prior 
to performing the ECG.  
 


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A central lab, eResearch Technology, Inc. (ERT), will provide ECG equipment, supplies and site 
training.  In addition, ERT will process ECGs received by the sites and report results via a secure 
study portal.  The ECG results will be interpreted by a qualified health professional (evaluator) 
and the interpretation reported either directly on the tracing or in a separate report.   The evaluator 
will interpret the results of every ECG and define the ECG as “normal” or “abnormal”.  Variations 
such as minor ST changes (i.e., <0.5mm depression) and early re-polarization are considered 
normal.  
 
The investigator must review the evaluator’s interpretation of each subject’s screening ECG prior 
to Baseline (Visit 2). The investigator will review the evaluator’s interpretation of all ECG reports 
in a timely manner and comment on the clinical relevance of any result that is defined by the 
evaluator as abnormal.  
 
Any abnormalities that are, in the opinion of the investigator, clinically significant, must be 
reported as history if found prior to the start of the first study medication application or as an AE 
if found after the start of the first study medication application (see Section 9.1.1). 
 
 
Other Assessments 
8.5.1. 
Demographics, Medical History and Alopecia Areata History 
During the screening visit, the investigator or designee will interview each subject to obtain 
demographic information including date of birth, sex at birth, Fitzpatrick skin type, race and, if 
appropriate, ethnicity. The investigator or designee will interview each subject to obtain medical 
history information related to all medical conditions, surgeries and disease states that, at screening: 
are ongoing, require concomitant therapy or are, in the opinion of the investigator, relevant to the 
subject’s study participation.  In addition, the medical history of women who are not of 
childbearing potential should reflect the reason e.g. post-menopausal for 1 year or greater, bilateral 
tubal ligation, or hysterectomy.  The investigator or designee will also obtain an AA history at 
screening (APPENDIX 2). 
8.5.2. 
Photographic Assessment 
A qualified investigational staff member will take standardized photographs of the scalp at baseline 
and then monthly during the double-blind period and if the subject is continuing in the OLE, OLE 
Visits 3-6 and OLE Visit 1 (according to the Schedule of Assessments), if there is a significant 
change from the last double-blind study visit.  The photographs are to document the baseline hair 
loss and hair growth during treatment.  In addition, a target patch will be identified and 
photographed.  Equipment, supplies, training and detailed instructions for obtaining and managing 
photographs will be provided by Canfield Scientific to the investigational center prior to the 
initiation of subject enrollment. 
 
 
ADVERSE EVENTS 
Adverse events will be monitored throughout the study and reported on the appropriate Aclaris 
Therapeutics, Inc. AE eCRF.   
 


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Definitions 
9.1.1. 
Adverse events (AE) 
An AE is any untoward medical occurrence in a subject administered a study medication(s) and 
which does not necessarily have a causal relationship with the study medication.  An AE can 
therefore be any unfavorable and unintended sign or symptom associated with the use of a study 
medication (including an abnormal laboratory finding), whether or not related to the study 
medication.  
 
Thus, any new, clinically significant worsening of an existing sign, symptom or disease, should be 
considered an AE.  
 
Every new episode or clinically significant worsening of a chronic condition (e.g., headaches, 
seasonal allergies, depression, or 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 treatment should be reported as 
medical history, not as an AE. 
 
9.1.2. 
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 were 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 


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emergency room or at home for allergic bronchospasm, blood dyscrasia or convulsions that do not 
result in hospitalization. 
 
9.1.3. 
Unexpected adverse event 
An AE is considered unexpected if it is not listed in the Investigator Brochure or is not listed at 
the specificity or severity that has been observed. 
 
9.1.4. 
Adverse event reporting period 
The investigator must start reporting non-serious AEs with the subject’s first study medication 
application and continue reporting until the end of the subject’s last study visit. Reporting for SAEs 
must start when the subject signs the ICF and continue until the end of the subject’s last visit. 
 
9.1.5. 
Severity 
The investigator is to define the severity of each AE using the following definitions as a guideline. 
The investigator will consider the range of the possible severity of the event and identify the 
severity that is the most appropriate according to her/his medical judgment. 
 
Mild – Awareness of signs or symptom, but easily tolerated 
Moderate – Discomfort, enough to cause interference with usual activity 
Severe – Incapacitating with inability to perform usual activity. 
9.1.6. 
Relationship to study medication 
The investigator will determine if there is a reasonable causal relationship between the study 
medication and an AE or not. The investigator will use her/his best medical judgment and consider 
all relevant factors (e.g., temporal relationship, location of the event, the subject’s relevant medical 
history, concomitant therapies and concurrent conditions) to determine the relationship of the AE 
to the study medication. The investigator will define the relationship of an AE to the study 
medication by selecting one of the following categories: 
 
Related – There is a reasonable causal relationship between the study medication and the 
AE. 
 
Not Related – There is not a reasonable causal relationship between the study medication 
and the AE. 
The expression “reasonable causal relationship” is meant to convey in general that there are facts 
(evidence) or arguments to suggest a causal relationship (International Conference on 
Harmonization [ICH] E2A). 
 


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Reporting Procedures 
9.2.1. 
Procedures for reporting adverse events 
At each post-enrollment visit, the investigator will question the subject to elicit AEs using a non-
directive question such as “Has there been any change in your health since the previous study 
visit?”  If appropriate, based on the subject’s response to non-directed questioning to elicit AEs, 
the investigator will follow-up with directed questions and appropriate evaluations.  
 
Any AE noted during the reporting period must be reported in the source documents and on the 
appropriate AE eCRF. AEs that are defined as “Not Related” to the study medications will be 
followed until they are resolved or until the subject’s last study visit. AEs that are defined as 
“Related” to the study medications will be followed until they are resolved or, if not resolved 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. 
 
9.2.2. 
Procedure for reporting a serious adverse event 
Upon becoming aware of a SAE occurring during the AE reporting period, whether or not related 
to the study medications, the investigator must: 
 
1. 
Take the appropriate medical action to ensure the subject’s safety. 
2. 
Immediately inform the 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). 
 


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9.2.3. 
Safety Monitoring Discontinuation Criteria 
Any subject who develops any of the following ECG findings during the active treatment phase 
will be instructed to stop study medication and will be withdrawn from the study: 
• A post-study medication ECG result where the evaluator’s interpretation shows any of the 
following: 
o Clinically significant rhythm disturbance other than sinus rhythm or ectopic 
supraventricular rhythm (ectopic atrial rhythm) 
o Clinically significant conduction disturbance including PR >240msec, pre-
excitation (delta wave and PR <120msec), second degree or higher AV block  
o New finding of QRS>120ms (if not present at screen.  For example, subjects with 
Right Bundle Branch Block at screening would not need to be withdrawn from the 
study if their subsequent ECGs remained unchanged). 
o Evidence of QT-interval prolongation, defined as an increase in the QTcF 
interval>60ms from Visit 1 
o Acute signs of ischemia or infarction 
o Any ECG abnormality which may, in the opinion of the investigator, represent a 
new medical issue of concern 
Site staff must perform protocol-required procedures for trial discontinuation and follow-up.  
 
 


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9.2.4. 
Study Medication Interruption and Discontinuation Criteria 
9.2.4.1 
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 2. 
 
Table 2:  Study Medication Interruption Criteria 
Laboratory Test 
Hold Study Medication if: 
Resume Study Medication if: 
WBC count 
< 2 x 109/L 
≥ 2.5 x 109/L 
ANC 
< 1 x 109/L 
≥ 1.5 x 109/L 
Lymphocyte count < 0.5 x 109/L 
≥ 0.75 x 109/L  
Platelet count 
< 75 x 109/L 
≥ 100 x 109/L 
Hemoglobin 
< 8 g/dL or a decrease > 2g/dL 
≥ 10 g/dL 
AST or ALT 
> 3 x ULN 
< 2 x ULN or within 20% of Baseline values 
Serum creatinine 
>2 x ULN 
<1.5 x ULN or within 10% of Baseline value 
 
If a subject has one or more of the abnormal laboratory values noted in Table 2, the investigator 
or designee upon receipt and review of the central laboratory report should instruct the subject to 
hold study medication applications. The investigator or designee should ask the subject about 
symptoms, concomitant illnesses and medications and repeat the test(s) as soon as possible.  The 
Medical Monitor must be notified of dose interruptions due to SAEs considered related to study 
medication or laboratory abnormalities noted in Table 2.  
If the retest confirms the abnormal laboratory value, then the study medication should continue to 
be held followed by repeat testing once a week or sooner at the discretion of the investigator.  The 
subject should be followed until the laboratory abnormality(s) return to normal or to baseline 
values.    
9.2.4.2 
Study Medication Discontinuation 
Study medication should be permanently discontinued in the event of any of the following: 
• Severe infection requiring parental antimicrobial therapy or hospitalization 
• Symptomatic herpes zoster 
• Malignancy – except for non-melanoma skin cancer (SCC or BCC) not in or near the 
treatment area 
• Anaphylactic or severe allergic reaction 
• WBC Count: < 1 x 109/L or second occurrence of < 2 x 109/L 
• ANC:< 0.5 x 109/L or second occurrence of < 1 x 109/L 
• Lymphocyte count:< 0.3 x 109/L or second occurrence of < 0.5 x 109/L  
• Platelet count: < 50 x 109/L or second event of < 75 x 109/L - in each case, value should be 
confirmed by retesting before treatment discontinuation 


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• Hemoglobin: < 6.5 g/dL or second occurrence of < 8 g/dL - in each case, value should be 
confirmed by retesting before treatment discontinuation 
• AST or ALT: 
o > 5 x ULN persisting for 2 weeks of study medication interruption or second 
event of > 5 x ULN 
o > 3 x ULN with total bilirubin >2 x ULN or symptoms of hepatocellular  
injury (fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, 
rash and/ or eosinophilia (>5%). 
• 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. 
 
PREGNANCY 
 
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 and a negative UPT at baseline prior to randomization. 
 
 
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- 
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) 
• intrauterine hormone-releasing system (IUS) 
• vasectomized partner1 
• sexual abstinence2 


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1Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner 
of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical 
success.  
2 Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study treatments. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle 
of the subject. 
 
WOCBP must be on a highly effective method of birth control for the following timeframes prior 
to study entry:  
• Implants (on a stable dose for ≥30 days) 
• Injectables (on a stable dose for ≥30 days) 
• Patches (on a stable dose for ≥30 days) 
• Combined oral contraceptives (on a stable dose for ≥30 days) 
• Intrauterine devices (inserted for ≥30 days). 
 
Prior to trial enrollment, WOCBP must be advised of the importance of avoiding pregnancy during 
trial participation and of the potential risk factors associated with pregnancy while in the study.  
The subject must sign an informed consent/ assent form documenting this discussion.  During the 
trial, all WOCBP will be instructed to contact the investigator immediately if they suspect they 
might be pregnant (e.g., missed or late menstrual period). 
 
If a subject or investigator suspects that the subject may be pregnant prior to study medication 
administration, the study medication must be withheld until the results of a pregnancy test are 
available.  If pregnancy is confirmed, the subject must not receive study medication and must be 
discharged from the study.  
 
If, following study medication administration, it is determined that the subject may have been or 
was pregnant at the time of study medication exposure (including at least 2 days after study 
medication administration) the investigator must immediately notify the Aclaris Therapeutics, Inc. 
Medical Monitor and record the event on a pregnancy surveillance form. While not an AE or SAE, 
the investigator must report every pregnancy using a pregnancy surveillance form and follow the 
reporting procedures described for SAE reporting. 
Protocol-required procedures for trial discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy (e.g., x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated. In addition, the investigator must report 
to Aclaris Therapeutics, Inc.’s Medical Monitor on the pregnancy surveillance form, follow-up 
information regarding the course of the pregnancy, including perinatal and neonatal outcome. 
Infants should be followed for a minimum of six weeks. 
  
 
STATISTICAL ANALYSES 
The primary analysis will be conducted when all subjects have completed the double-blind period.   


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Sample Size and Power Calculations 
The planned sample size is 120 subjects.  Since this is the first multicenter study evaluating the 
effect of ATI-50002 Topical Solution in subjects with stable patchy alopecia areata, the sample 
size was based upon feasibility issues rather than on a formal power calculation.    However, data 
from 120 subjects (40 per group), utilizing LOCF for missing data, provides 80% power to detect 
a 24-point difference in percent change from baseline in SALT score between any two treatment 
groups.  This power computation was based upon the assumed standard deviation of 38%.  Data 
from a previous study NCT02197455 showed that the standard deviation in percent change from 
baseline in the SALT score is 30.3%.  The 38% standard deviation assumption used for this power 
computation was chosen to account for the increase in variance due to the lower baseline SALT 
entry criteria for this study as compared to NCT02197455. 
 
 
Analysis Populations 
The Intent to Treat (ITT) population is defined as all subjects who are randomized.  The Safety 
population is defined as all randomized subjects who applied at least 1 application of study 
medication. The Per-Protocol (PP) population is defined as all subjects who are randomized and 
do not have any major protocol violations.  Major protocol violations are defined as: 
1. Inclusion or Exclusion criteria not met 
2. Concomitant medications taken during the study that interfere with efficacy 
3. Did not apply at least 75% of study medication  
4. Did not complete Week 24 (Visit 10). 
 
 
Demographic and Baseline Characteristics 
Subject demographic and baseline characteristics, including medical and alopecia history, prior 
medications and therapies and physical examination findings will be summarized using descriptive 
statistics. 
 
For continuous variables, descriptive statistics (number, mean, standard deviation, standard error, 
median, minimum, and maximum) will be provided.  For categorical variables, subject counts and 
percentages will be provided.  Categories for missing data will be presented, if necessary. 
 
 
Efficacy Analyses 
   
11.4.1. 
Primary Efficacy Analyses 
The primary efficacy variable will be the percent change from baseline in the SALT score at Week 
24 (Visit 10).  This represents the percentage of hair regrowth.  It will be calculated as the mean 
of the changes from baseline (Visit 2) SALT score to Week 24 (Visit 10) SALT score, divided by 
the baseline SALT score and expressed as a percentage.  Missing data for the primary endpoint 
will be imputed using Last Observation Carried Forward (LOCF) methodology.  The analysis will 
be conducted on the relative percent change from baseline over time including all visits using a 
mixed effect model repeated measures (MMRM).  The adjusted mean (LS Mean) for percent 
change from baseline in the SALT score at each visit, estimated from the MMRM, with the 
estimated standard error and 95% confidence interval (CI), will be presented in tabular and graphic 


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format. The difference in the adjusted means between treatment groups and the associated 95% CI 
of the difference will be provided.  No adjustment for multiplicity will be made.  The model will 
include fixed effect terms for treatment, study visit, baseline SALT score group (<50, >=50), and 
treatment by SALT group interaction.  The primary analysis will be based on the Intent-to-Treat 
(ITT) population.  Statistical significance for primary efficacy endpoint will be declared if at least 
one treatment group comparison at the Week 24 visit has a two-sided p-value less than or equal to 
0.05.  
 
11.4.2. 
Secondary Efficacy Analyses 
A secondary sensitivity analysis of the primary endpoint will be conducted using the PP 
population.  This analysis will use the same methodology as described for the primary analysis 
just applied to the PP population. 
 
The secondary efficacy endpoints include: the percent change from baseline in the ALODEX score 
(percent regrowth); the mean change from baseline in SALT and the mean change from baseline 
in ALODEX, the proportion of subjects achieving a ≥ 50% hair regrowth compared with baseline 
using a separate model for SALT and for ALODEX scores; change from baseline in the AAA 
(Clinician and Subject), PhGIS, SGIS, AIA, treatment satisfaction questionnaires; and DLQI.  
Various secondary responder efficacy endpoints will be defined based upon the SALT score, the 
ALODEX scores and the AAA (Clinician and Subject) questionnaires.  Details of these responder 
definitions will be specified in the statistical analysis plan (SAP).  Global Impression of Change 
(Clinician and Subject) at Week 24 (Visit 10) will be used in the psychometric evaluation of the 
scores from the AAA (CR and SR), respectively.   All secondary efficacy endpoints will be 
analyzed using the ITT population.    The analysis of the percent change in ALODEX score 
analysis will use the same methodology as specified for the primary efficacy analysis.  Other 
parameters will be analyzed as detailed in the SAP.  
 
 
Safety Analyses 
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 treatment and Medical Dictionary for Regulatory Activities 
(MedDRA) System Organ Class. Vital signs and clinically significant abnormal laboratory 
results will also be tabulated and presented by treatment group.  
 
Data from all randomized subjects will be presented and summarized. Safety summaries by study 
treatment group will include listings by study medication of adverse events incidences within 
each MedDRA System Organ Class, and changes from pre-application values in vital signs. 
Adverse event summaries will be presented by study medication showing the proportion of 
subjects experiencing adverse events, both overall and by MedDRA System Organ Class. 
 
 
Open-Label Extension Analyses 
OLE endpoints will include safety variables, efficacy variables [(change from baseline in SALT, 
ALODEX at long-term visits), (change from baseline in AAA-SR, AAA-CR, and SGITS)].  
 


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Exploratory Biomarker Analyses (Select Sites Only) 
11.7.1. 
ALADIN Scores (Select Sites Only)              
The cytotoxic T-lymphocyte infiltration (CTL), Interferon (IFN-gamma), and hair keratin (KRT) 
ALADIN scores will be calculated for each scalp biopsy sample as described in (Xing et al, 
2014, Jabbari 2016).  Change in ALADIN scores within individual subjects will be assessed 
between Baseline (Visit 2), Week 4 (Visit 5), and Week 24 (Visit 10).   
 
11.7.2. 
Scalp Biopsy for Histology and Immunology (Select Sites Only) 
Scalp punch-biopsies will be formalin-fixed and paraffin-embedded and will be sectioned both 
vertically and horizontally by a qualified dermatopathologist.  Specimens will be stained with 
hematoxylin and eosin (H&E) for “routine” histopathologic evaluation that will include (but is not 
limited to) diagnosis and evaluation of the presence, quantity, location, and quality of any hair, 
hair follicles, and inflammatory infiltrate present.  Additionally, immunohistochemical (IHC) 
stains will be employed to identify immune cell populations (e.g., Lymphocytes, cytotoxic T-
lymphocytes (CTLs)), and hair-specific keratins.  IHC stains to assess inflammatory responses will 
include but not be limited to CD8, HLA-DR and ICAM-1.  Data will be presented as percent 
change from baseline in the number of cells/ high power field in regions of interest (peribulbar 
areas) and in percent change from baseline in the number of cells/mm2. 
 
11.7.3. 
Blood for Immunology (Select Sites Only) 
Blood samples will be stained with cell surface antibodies for fluorescence acquisition cell sorting 
(FAC) analysis.  FACS experiments will allow for assessment of the subset and activation status 
of immune cells involved in AA. 
 
11.7.4. 
Clinical Correlative Studies (Select Sites Only) 
Previous studies in human AA have reported increased NKG2DL expression and augmented 
expression of IFN response genes in the target hair follicle end organ, and elevated NKG2D 
expression in circulating CD8 T-cells and NK cells (Ito et al, 2008; Petukhova et al, 2010). 
 
The study will include assessment at select sites of AA biomarkers at baseline and during treatment 
to correlate treatment and disease status with: 
1. Histological improvement with reduced T-cell peribulbar infiltrates. 
2. Declines in circulating and peribulbar CD8+NKG2D+ infiltration and in follicular hair 
follicle NKG2DL expression. 
3. Reduced IFN inflammatory biomarkers in the skin and blood. 
 
 
TRAINING, MONITORING, DATA MANAGEMENT AND QUALITY 
ASSURANCE 
 
Training 
For each investigational center, there will be an initiation visit prior to enrolling any study subjects. 
 


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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. 
 
 
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. representative’s designee and/or 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. 
 
 
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. 
 
 
Quality Assurance 
The study is conducted under the sponsorship of Aclaris Therapeutics, Inc. in compliance with the 
applicable regulatory requirements as well as applicable ICH guidelines, Declaration of Helsinki, 
and in respect of the Aclaris Therapeutics, Inc. and/or sub-contractor SOPs for study conduct and 
monitoring. 
 
Audits may be carried out by Aclaris Therapeutics, Inc. or Aclaris Therapeutics, Inc.’s 
representatives, and inspections may be performed by regulatory authorities or IRB/ECs before, 
during or after the study.  The investigator will provide the auditing/inspecting group direct access 
to all study records (e.g., eCRFs, subject medical records, study medication dispensing records) 
and the investigational center study facilities. The investigator and study staff will be available and 
will assist the auditing/inspecting groups as appropriate.  
 


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ETHICS AND GENERAL STUDY CONDUCT CONSIDERATIONS 
 
Institutional Review Board (IRB)/Ethics Committee (EC) 
This protocol, informed consent/ assent 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. 
 
 
Ethical Conduct of the Study 
The rights, safety and well-being of the subjects are the most important considerations in this study 
and take priority over the interests of society and science.  
 
This study will be conducted in accordance with the ethical principles originating from the 
Declaration of Helsinki, the ICH E6 GCP guideline, local regulatory requirements and, at US 
investigational centers, in compliance with the HIPAA. The study will be conducted in compliance 
with the IRB/EC approved version of the protocol and any applicable amendments. 
 
 
Subject Information and Consent/ Assent 
All subjects who participate in this study must be fully informed about the study in accordance 
with the GCPs, federal regulations, local regulations and, at US investigational centers, with 
HIPAA.  The ICF/ Assent will contain all the required elements in compliance with the current 
ICH E6 GCP guideline and local regulatory requirements. The investigator must have a defined 
process for obtaining voluntary informed consent from every subject.  
 
The ICF/ Assent Form, approved by an IRB/EC, will be fully explained to the subject and the 
parent/ legal guardian, if applicable.  Prior to any study related procedures, including washout from 
therapies, the subject will voluntarily sign and date the ICF/ Assent Form. The investigator must 
maintain each subject’s ICF/ and if applicable the Assent Form in the investigational center’s study 
file and must provide each subject and if applicable parent/ legal guardian with a copy of the signed 
and dated ICF/ Assent Form. 
 
 
Study Conduct and Protocol Amendments 
With the exception of eliminating an immediate hazard to a subject, the investigator should not 
deviate from the protocol or implement any changes without prior written approval from the 
Aclaris Therapeutics, Inc.’s representative or designee and prior review and documented approval 
from the IRB/EC. 
 
Changes that involve only logistical or administrative changes are allowed.  The investigator 
should document and explain any deviation from the protocol.  A protocol deviation is a non-
adherence to protocol-specific study procedures or schedules that does not increase the risk to a 
study subject and does not affect the scientific integrity of the study.   
 


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A protocol violation is defined as any divergence from the protocol-specific study procedures or 
schedules that may results 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. 
 
 
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. 
 
 
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. 
 
 
Data Collection and Archiving 
13.7.1. 
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. 
 
13.7.2. 
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/ 
assent.  Any AEs must be completely documented. Source documentation includes results of any 
diagnostic tests conducted during the study.   
 
13.7.3. 
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. 
 


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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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REFERENCES 
ATI-50002 Topical Solution Investigator Brochure.  Data on File at Aclaris Therapeutics, Inc. 
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.  
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. 
Ito, T., Ito, N., Saatoff, M., Hashizume, H., Fukamizu, H., et al. Maintenance of hair 
follicle immune privilege is linked to prevention of NK cell attack. J. Investig Dermatol. 
2008:128; 1196–1206. 
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.  
McElwee KJ, Boggess D, King, B, Sundbrg JP.  Experimental Induction of Alopecia Areata-Like 
Hair Loss in C3H/HeJ Mice Using Full-Thickness Skin Grafts.  J Invest Dermatol. 1998. 
111:797–803. 
 


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Olsen EA.  Investigative guidelines for alopecia areata.  Dermatol Ther. 2011:24;311-319. 
Olsen EA and Canfield D.  SALT II: A New Take on the Severity of Alopecia Tool (SALT) for 
Determining Scalp Hair Loss.  J Am Acad Dermatol. 2016;75(6):1268-1270.  
Olsen EA, Green C, Hordinsky M, Bergfeld W, McMichael A, Callender V, Washenik K, 
Cotsarelis G, Shapiro J, Roberts J, Wolfe S, Cherill D, Canfield D.  Alopecia Density and Extent 
(ALODEX):  A new method for assessing severity of hair loss in alopecia areata.  Submitted for 
publication. 
Petukhova, L., Duvic, M., Hordinsky, M., Norris, D., Price, V., et al.  Genome-wide 
association study in alopecia areata implicates both innate and adaptive immunity. 
Nature. 2010:466, 113–117.  
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. 
Pratt CH, King LE Jr, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. 
Nat Rev Dis Primers. 2017 16;3:17011. 
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. 
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., 2003a. Histopathologic features of alopecia areata: a new look. Arch. 
Dermatol. 139, 1555–1559.  
Whiting, D.A., 2003b. Histopathologic features of alopecia areata. 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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:  Subject Instructions for Study Medication Application to the Patchy Areas 
of the Scalp 
Preparation and General Instructions:  
1. Gather a clean washcloth and towel, the study medication bottle, and disposable dropper. 
1. Hair and scalp should be clean (free of any hair and scalp styling products), and dry or at least 
towel-dried before applying study medication.  Ensure that your scalp is as dry as possible.  A 
clean scalp will allow the study medication to penetrate down into the scalp to ensure you are 
getting the best application.  The treatment areas of the scalp should be washed using your normal 
cleansing products at least an hour prior to study medication application, at least once a day to 
prevent accumulation of study medication on your skin.    
2. Wash your hands with soap and water before and after using this study medication.  
3. You will apply a thin layer of study medication to each area of scalp hair loss as instructed by the 
study doctor or the study staff.  Keep applying study medication to the areas of hair loss 
throughout the study, even if scalp hair is regrowing in these areas. If you experience new areas 
of scalp hair loss (for example, areas of the scalp with active hair shedding and abnormal 
sensations that in your experience is a sign of scalp hair loss) discuss these new areas with the 
study Doctor so they can be appropriately documented before applying study medication. 
4. The amount of study medication you will apply during one treatment is a total of __ mL (__ 
-1mL droppers).   
5. Avoid study medication contact with the eye.  If the study medication gets on any part of your 
body other than your scalp, rinse the area well with water.  
6. You will apply study medication twice-a-day, approximately 8 to 12 hours apart.   
7. Remember to bring your study medication bottles both used and unused to each study visit. 
Instructions For Select Sites Only:   
8. Apply your study medication in the evening before your Week 4, and Week 24 visits and note the 
time.  Do not apply your morning dose of study medication until after your office visit. 
9. Do not apply study medication to the area where the biopsy was performed until the study doctor 
indicates you are allowed. 
 
Study Medication Application: 
1. Draw up exactly 1 mL of study medication into the dropper. The medication level should be at 
the 1mL line.  
2. During study medication application, keep your head tilted back to avoid any study medication 
running into your eyes.   
3. Starting with your Target Patch, squeeze a few drops of study medication onto the center of the 
patch of your scalp and gently rub the study medication into your scalp.  Keep applying a few 
drops and rubbing into your scalp until the entire Target patch and about ½” margin around 
the patch is covered with a thin film of study medication. 
4. Draw up additional study medication in the dropper – 1mL at a time to cover the entire patchy 
areas on your scalp with hair loss. 
5. Select the next area of hair loss, squeeze a few drops of study medication onto the center of the 
patchy area of hair loss, and gently rub the medication into your scalp. Keep applying a few drops 
until the entire patch of scalp hair loss and about a ½ inch margin around the patch is 
covered with a thin film of study medication. Repeat until all affected areas are covered with a 
thin film of medication using one dropper per treatment application. 
6. Replace the screw top cap and make sure it is closed tightly.  Dispose of the used dropper(s). 
7. It is important to continue to apply study medication to the areas of hair loss throughout the study, 
even if there is hair growth in the area(s).   
8. Wash your hands after using this product to prevent any residue being left on your hands. 


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9. Allow the study medication to dry for at least 15 minutes before you apply any styling products to 
the hair.  All topical products applied to the hair and scalp must be reviewed and approved by 
your study doctor before use. 
10. If you missed a dose or doses, record on your subject compliance record and tell the study staff at 
your next visit.     
11. Do not wash your hair or scalp for at least 6 hours after applying study medication.  
Wigs and Hairpieces 
1. Wigs and hairpieces may be worn while participating in the study but must be appropriately 
managed. 
2. Wigs or hairpieces should not be worn until the study medication is completely dry on the scalp.  
Thus, wigs or hairpieces should not be reapplied for at least 15 minutes after the study drug has 
been applied.  
3. Wigs and hairpieces will need to be removed at each study visit to allow the study doctor to 
evaluate your scalp and hair loss.  Any hairpieces that may be difficult to remove will prevent you 
from participating in the study.  Do not have semi-permanent or difficult to remove hairpieces 
placed during the study.  Hair “weaves” that only involve areas of the scalp that continue to have 
hair may be accepted on a case by case basis. 
4. If scalp irritation develops during the study, it may be necessary to temporarily stop wearing of a 
hairpiece or wig.  The study doctor will discuss this with you should scalp irritation develop. 
Missed Doses: If you miss a dose of this study medicine, apply it as soon as possible. However, if it is 
almost time for your next dose, skip the missed dose, and go back to your regular dosing schedule. 
 
Storage: Store the medicine in the original glass bottle, in the carton provided, at room temperature, away 
from heat, moisture, and direct light. Keep from freezing.  Keep study medication and used droppers out 
of the reach of children. 


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:  Parent/ Subject Instructions for Study Medication Application to the 
Entire Scalp 
Preparation and General Instructions:  
2. Gather a clean washcloth and towel, the study medication bottle, disposable dropper and gloves 
(parent application only).  Parents must wear gloves when applying study medication to their 
child’s scalp.  
3. Hair and scalp should be clean (free of any hair and scalp styling products), and dry or at least 
towel-dried before applying study medication.  Ensure that your scalp is as dry as possible.  A 
clean scalp will allow the study medication to penetrate down into the scalp to ensure you are 
getting the best application.  The scalp should be washed using your normal cleansing products at 
least an hour prior to study medication application, at least once a day to prevent accumulation of 
study medication on your skin.    
4. Wash your hands with soap and water before and after using this study medication.   
5. You will apply a thin layer of study medication to the entire scalp as instructed by the study 
doctor or the study staff.  Once medication has been applied to all current patchy areas, part hair 
into approximately 4 sections (from front to back). Take each section one by one and apply up to 
1mL to the scalp part and massage the study medication into the scalp from the part to the sides 
until the entire scalp is covered in a thin film of study medication.  Keep applying study 
medication throughout the study, even if scalp hair is regrowing. If you experience new areas of 
scalp hair loss (for example, areas of the scalp with active hair shedding and abnormal sensations 
that in your experience is a sign of scalp hair loss) discuss these new areas with the study Doctor 
so they can be appropriately documented. 
6. The amount of study medication you will apply during one treatment is a total of __ mL (__ 
-1mL droppers).   
7. Avoid study medication contact with the eye.  If the study medication gets on any part of your 
body other than your scalp, rinse the area well with water.  
8. You will apply study medication twice-a-day, approximately 8 to 12 hours apart.   
9. Remember to bring your study medication bottles both used and unused to each study visit. 
Instructions For Select Sites Only:   
10. Apply your study medication in the evening before your Week 4, and Week 24 visits and note the 
time.  Do not apply your morning dose of study medication until after your office visit. 
11. Do not apply study medication to the area where the biopsy was performed until the study doctor 
indicates you are allowed. 
 
Study Medication Application: 
1. Draw up exactly 1 mL of study medication into the dropper. The medication level should be at 
the 1mL line.  
2. During study medication application, keep your head tilted back to avoid any study medication 
running into your eyes.   
3. Starting with your Target Patch, squeeze a few drops of study medication onto the center of the 
patch of your scalp and gently rub the study medication into your scalp. Once medication has 
been applied to all current patchy areas, part hair into approximately 4 sections (from front to 
back). Apply up to 1 mL to the scalp of each parted section from front to back and massage the 
study medication into the scalp from the part to extending to the sides until the entire scalp is 
covered in a thin film of study medication.     
4. Replace the screw top cap and make sure it is closed tightly.  Dispose of the used dropper(s). 
5. It is important to continue to apply study medication to the entire scalp throughout the study, even 
if there is hair growth.   
6. Wash your hands after using this product to prevent any residue being left on your hands. 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 69 of 82 
Version 9.0, Date: 09APR2019 
7. Allow the study medication to dry for at least 15 minutes before you apply any styling products to 
the hair.  All topical products applied to the hair and scalp must be reviewed and approved by 
your study doctor before use. 
8. If you missed a dose or doses, record on your subject compliance record and tell the study staff at 
your next visit.     
9. Do not wash your hair or scalp for at least 6 hours after applying study medication.  
Wigs and Hairpieces 
1. Wigs and hairpieces may be worn while participating in the study but must be appropriately 
managed. 
2. Wigs or hairpieces should not be worn until the study medication is completely dry on the scalp.  
Thus, wigs or hairpieces should not be reapplied for at least 15 minutes after the study drug has 
been applied.  
3. Wigs and hairpieces will need to be removed at each study visit to allow the study doctor to 
evaluate your scalp and hair loss.  Any hairpieces that may be difficult to remove will prevent you 
from participating in the study.  Do not have semi-permanent or difficult to remove hairpieces 
placed during the study.  Hair “weaves” that only involve areas of the scalp that continue to have 
hair may be accepted on a case by case basis. 
4. If scalp irritation develops during the study, it may be necessary to temporarily stop wearing of a 
hairpiece or wig.  The study doctor will discuss this with you should scalp irritation develop. 
Missed Doses: If you miss a dose of this study medicine, apply it as soon as possible. However, if it is 
almost time for your next dose, skip the missed dose, and go back to your regular dosing schedule. 
 
Storage: Store the medicine in the original glass bottle, in the carton provided, at room temperature, away 
from heat, moisture, and direct light. Keep from freezing.  Keep study medication and used droppers out 
of the reach of children. 
  


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 70 of 82 
Version 9.0, Date: 09APR2019 
 :  Parent/ Subject Instructions for Study Medication Application to the 
Eyebrow during the Open-Label Extension 
General Instructions: 
1. Before application of study medication, your 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 60 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 eyebrow areas, 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. 
 
 
 


Protocol: ATI-50002-AA-201 
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Page 71 of 82 
Version 9.0, Date: 09APR2019 
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. 
 
 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 72 of 82 
Version 9.0, Date: 09APR2019 
:  Alopecia Areata History  
The following AA history will be obtained: 
 
1. Onset date of alopecia 
 
2. Onset date of current episode of patchy alopecia areata 
 
3. Did the subject use previous therapies for Patchy AA? 
 
a. If Yes, indicate which therapies 
1. Topical immunotherapy 
2. Corticosteroids 
3. Systemic Steroids 
4. DMARDS 
5. Biologics or immunosuppressants 
6. Plaquenil 
7. PDT 
8. Janus kinase inhibitors 
9. Phototherapy 
10. Laser therapy 
11. Narrow-band UVB 
12. Other 
 
 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 73 of 82 
Version 9.0, Date: 09APR2019 
:  Fitzpatrick’s Skin Type Chart 
Fitzpatrick Skin Type 
Description (Sunburn & Tanning History According to Skin Type) 
Skin Type 
Always Burns; never tans (pale white skin) 
I 
Burns easily; tans minimally (white skin) 
II 
Burns moderately; tans uniformly (light brown skin) 
III 
Burns minimally; always tans (moderate brown skin) 
IV 
Rarely burns; tans profusely (dark brown skin)  
V 
Never burns; deeply pigmented (dark black Skin) 
VI 
 
 
 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 74 of 82 
Version 9.0, Date: 09APR2019 
:  Alopecia Scalp Appearance Assessment for AA Patchy (AAA) (Subject) 
Prior to administering the questionnaires to the subject, review the target patch identified at 
baseline.  Subject should be provided a handheld mirror to adequately view the target patch.  
Ensure that the subject clearly understands the full location of the target area (especially in cases 
where the patch may have regrown hair). 
 
Alopecia Scalp Appearance Assessment for Patchy AA: Subject Rating (SR) 
 
Instructions for item 1: Please mark an “X” in the box (☒) that best describes the appearance 
of the target patch right now.  Please select the one response that best represents your answer. 
 
Full hair, scalp of the target patch completely covered with hair 
Most hair, scalp of the target patch mostly covered with hair 
Some hair, scalp of the target patch somewhat covered with hair 
A little hair, scalp of the target patch mostly exposed 
No hair, scalp of the target patch completely exposed 
 
Instructions for item 2: Please mark an “X” in the box (☒) that best describes the appearance 
of your whole scalp right now.  Please select the one response that best represents your answer. 
 
Full hair, whole scalp completely covered with hair 
Most hair, whole scalp mostly covered with hair 
Some hair, whole scalp somewhat covered with hair 
A little hair, whole scalp mostly exposed 
No hair, whole scalp completely exposed 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 75 of 82 
Version 9.0, Date: 09APR2019 
:  GLOBAL IMPRESSION OF SEVERITY - Subject 
SUBJECT GLOBAL IMPRESSION OF SEVERITY (SGIS) 
 
Please mark an “X” in the box (
) that best describes the severity of your patchy alopecia areata 
right now. 
 
Overall, how severe is your patchy alopecia areata right now? 
☐ Mild 
☐ Moderate 
☐ Severe 
☐ Very Severe 
☐ Extremely Severe 
 
 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 76 of 82 
Version 9.0, Date: 09APR2019 
:  SUBJECT SATISFACTION QUESTIONNAIRE 
The investigator or study staff will review with the subject that this questionnaire is related to 
satisfaction with the outcome of the treatment (study medication). 
 
GLOBAL IMPRESSION OF TREATMENT SATISFACTION 
 
Please mark an “X” in the box (
) that best describes how satisfied you are with the treatment 
you received in this study for your patchy alopecia areata. 
 
How satisfied or dissatisfied are you with the treatment you received in this study for your 
patchy alopecia areata? 
 
☐ Extremely satisfied 
☐ Moderately satisfied 
☐ A little satisfied 
☐ Neither satisfied or dissatisfied 
☐ A little dissatisfied 
☐ Moderately dissatisfied 
☐ Extremely dissatisfied 
 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 77 of 82 
Version 9.0, Date: 09APR2019 
:  ALOPECIA IMPACT ASSESSMENT 
Alopecia Impact Assessment (AIA) 
Instructions: The following questions are about your alopecia.  For each question, please select the box 
(☒) below the number that best describes your experience with alopecia during the past seven days.  
There are no right or wrong answers. 
1. During the past seven 
days, how bothersome 
was it to cover your hair 
loss (e.g., wearing a wig, 
using makeup to fill in 
eyebrows, wearing hats)? 
Not at all 
bothersome 
 
Extremely 
bothersome 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2. During the past seven 
days, how worried were 
you about your 
appearance due to your 
hair loss? 
Not at all 
worried 
 
Extremely 
worried 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3. During the past seven 
days, how sad did you feel 
due to your hair loss? 
Not at all  
sad 
 
Extremely  
sad 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. During the past seven 
days, how much did your 
hair loss impact your 
confidence? 
Not at all 
impacted 
 
Extremely 
impacted 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. During the past seven 
days, how self-conscious 
did you feel due to your 
hair loss (e.g., feeling 
uncomfortable with 
hair/hair loss in public)? 
Not at all self-
conscious 
 
Extremely 
self-
conscious 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. During the past seven 
days, how embarrassed 
did you feel due to your 
hair loss (e.g., feeling 
awkward about, or 
ashamed of, hair loss)? 
Not at all 
embarrassed 
 
Extremely 
embarrassed 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 78 of 82 
Version 9.0, Date: 09APR2019 
7. During the past seven 
days, how unattractive did 
you feel due to your hair 
loss? 
Did not feel 
unattractive at all 
 
Felt 
extremely 
unattractive 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8. During the past seven 
days, how much did your 
hair loss limit your social 
activities (e.g., spending 
time with friends, going to 
a social event)? 
Not at all 
limited 
 
Extremely 
limited 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9. During the past seven 
days, how much did your 
hair loss limit your 
physical activities (e.g., 
going to the gym, 
swimming, playing 
sports)? 
Not at all 
limited 
 
Extremely 
limited 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10. During the past seven 
days, how bothersome 
was unwanted or negative 
attention from others due 
to your hair loss (e.g., 
staring, questions)? 
Not at all 
bothersome 
 
Extremely 
bothersome 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11. During the past seven 
days, how bothersome 
was your experience of 
getting sweat in your eyes 
due to your hair loss? 
Not at all 
bothersome 
 
Extremely 
bothersome 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12. During the past seven 
days, how bothersome 
was your experience of 
getting debris in your eyes 
due to your hair loss? 
Not at all 
bothersome 
 
Extremely 
bothersome 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
13. During the past seven 
days, how bothersome 
was your experience 
getting debris in your 
nose due to your hair 
loss? 
Not at all 
bothersome 
 
Extremely 
bothersome 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 79 of 82 
Version 9.0, Date: 09APR2019 
 :  DERMATOLOGY LIFE QUALITY INDEX 
The Investigator or study staff will remind the subject to think of their scalp hair loss instead of 
“skin problem” and “skin” in the questions below.   
 
DERMATOLOGY LIFE QUALITY INDEX 
 
When completing the questionnaire, think of your hair loss in place of “skin problem” and “skin” 
in the questions below. 
 
The aim of this questionnaire is to measure how much your skin problem has affected your life OVER 
THE LAST WEEK.  Please tick  one box for each question. 
 
1. Over the last week, how itchy, sore, painful or stinging has your skin been?  
Very much 
A lot 
A little 
Not at all 
 
2. Over the last week, how embarrassed or self conscious have you been because of your skin? Very 
much 
A lot 
A little 
Not at all 
 
3. Over the last week, how much has your skin interfered with you going shopping or looking after your 
home or garden?   
Very much 
A lot 
A little 
Not at all                                                
Not relevant 
      
4. Over the last week, how much has your skin influenced the clothes  
 
you wear? 
Very much 
A lot 
A little 
Not at all 
Not relevant 
 
 
5. Over the last week, how much has your skin affected any social or leisure activities? 
Very much 
A lot 
A little 
Not at all 
Not relevant 
 
6. Over the last week, how much has your skin made it difficult for you to do any sport? 
             Very much 
             A lot 
             A little 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 80 of 82 
Version 9.0, Date: 09APR2019 
             Not at all 
             Not relevant 
 
7. Over the last week, has your skin prevented you from working or studying? 
Yes, No, or Not relevant 
             If "No", over the last week how much has your skin been a problem at  work or studying? 
              A lot 
             A little 
             Not at all 
 
8. Over the last week, how much has your skin created problems with your partner or any of your close 
friends or relatives?  
             Very much 
             A lot 
             A little 
             Not at all 
             Not relevant 
 
9. Over the last week, how much has your skin caused any sexual difficulties? 
             Very much 
             A lot 
             A little 
             Not at all 
             Not relevant 
 
10. Over the last week, how much of a problem has the treatment for your skin been, for example by 
making your home messy, or by taking up time?  
              Very much 
              A lot 
              A little 
              Not at all 
              Not relevant 
 
 
 
Please check you have answered EVERY question. Thank you.  
AY Finlay, GK Khan, April 1992 www.dermatology.org.uk, this must not be copied without the permission of the authors. 
 
 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 81 of 82 
Version 9.0, Date: 09APR2019 
:  Select Sites Only- Scalp Biopsy 
All scalp punch biopsies will be performed by the investigator in a patchy area (not the Target 
area) at Baseline (Visit 2), Week 4 (Visit 5), and Week 24 (Visit 10) prior to application of study 
medication.  
 
The biopsy site will be anesthetized with an injection of 1% lidocaine with epinephrine. The 
lidocaine with epinephrine may be neutralized with bicarbonate to prevent stinging.  After 
approximately 1 minute, the physician will apply pressure to the biopsy site using a 4mm diameter 
skin punch (a sterile cylindrical tube with a sharp edge). The punch is twisted until the blade of the 
skin punch has pierced the epidermis and dermis of the skin and enters the subcutaneous fat. 
Depending on the thickness of the skin in the area being biopsied, the cylindrical blade may be 
buried to the hub (approximately 6mm in depth). After the blade has sufficiently cored or carved 
out a cylinder of skin, the skin punch is removed. Nontraumatic forceps are used to gently grasp 
the cored skin, pulling upward to remove the core and reveal the subcutaneous fat. Scissors are 
used to cut the cored tissue free from the underlying subcutaneous fat. Care should be taken to 
ensure that the specimen is cut well below the level of the hair follicle.  The specimen is placed 
immediately into the appropriate media. Once the specimen has been removed, pressure is applied 
to the biopsy site with a sterile 2 x 2 gauze. The biopsy site is then closed with several simple 
interrupted sutures. Either an absorbable or nonabsorbable suture may be used at the investigator’s 
discretion. Antibiotic ointment is applied and the area is covered with a standard Band-Aid or 
sterile gauze and paper tape. If the presence of adjacent hair makes adhesion of a bandage difficult, 
antibiotic ointment will be used without a covering. When necessary, a small pressure dressing 
may be applied. Subjects will be instructed in wound care, to avoid applying study medication to 
the biopsy site until the sutures are removed and will be advised to call the research unit if they 
have any concerning signs or symptoms during healing.  A follow-up visit will be scheduled 
approximately 2 weeks later, to remove sutures and examine the healing process of the biopsy site 
to ensure it is healing appropriately. 
 
 


Protocol: ATI-50002-AA-201 
Aclaris Therapeutics, Inc. 
 
 
Page 82 of 82 
Version 9.0, Date: 09APR2019 
:  Subject Global Impression of Change (SGIC) 
 (Please mark an “X” in the box ():  
 
1. Compared to your hair loss at the beginning of the study [before starting study 
medication], your alopecia is? 
 
1=Very much improved since starting study medication 
 
2=Much improved 
 
3=A little improved 
 
4=No change since starting study medication 
 
5=A little worse 
 
6= Much worse 
 
7=Very much worse since starting study medication 
 
 
 
 
 

SAP_000.pdf: 
Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-50002-AA-201  
Version Date: 19APR2019 
 
 
 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
Study Title:  
A Randomized, Double-Blind, Vehicle-Controlled Multicenter 
Study to Evaluate the Safety, Tolerability and Efficacy of ATI-
50002 Topical Solution Administered Twice-Daily for 6 Months 
in Adolescents and Adult Subjects with Stable Patchy Alopecia 
Areata with Optional Long-Term Open-Label Extension 
 
 
Phase: 
II 
 
 
Protocol No.: 
ATI-50002-AA-201  
 
 
Protocol Date(s): 
Version 1.0, 12JUL2017 
Version 2.0, 26JUL2017 
Version 3.0, 04JAN2018 
Version 4.0, 26APR2018 
Version 5.0, 11JUN2018 
Version 6.0, 08AUG2018 
Version 7.0, 10AUG2018 
Version 8.0, 26SEP2018 
Version 9.0, 09APR2019 
 
 
 
 
Analysis Plan Version and 
Date: 
Version 2.0, Final 19APR2019 
 
 
Prepared By: 
Vikki Roy, MS 
PharPoint Research, Inc. 
5003 S. Miami Blvd. 
Suite 100 
Durham, NC 27703 
 
 
 
Prepared For: 
Aclaris Therapeutics, Inc.  
640 Lee Rd  
Suite 200  
Wayne, PA 19087  
 
 
CONFIDENTIAL AND PROPRIETARY INFORMATION


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-50002-AA-201  
Version Date: 19APR2019 
 
 
 
 
CONFIDENTIAL 
Page 2 
19APR2019 
 
STATISTICAL ANALYSIS PLAN REVIEW AND APPROVAL 
 
This Statistical Analysis Plan has been prepared in accordance with team reviewers’ specifications.   
 
Prepared by: 
 
Vikki Roy, MS 
Senior Manager, Biostatistics 
PharPoint Research, Inc. 
 
Date 
 
 
Review:  
 
 
 
 
Amy Flynt, PhD 
Sr. Director, Consulting Operations, Biostatistics 
PharPoint Research, Inc. 
 
Date 
 
 
 
 
David Burt 
Sr. Director, Biostatistics 
Aclaris Therapeutics, Inc. 
 
Date 




Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-50002-AA-201  
Version Date: 19APR2019 
 
 
 
 
CONFIDENTIAL 
Page 3 
19APR2019 
 
TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN REVIEW AND APPROVAL .............................................. 2 
GLOSSARY OF ABBREVIATIONS ............................................................................................. 5 
1. 
INTRODUCTION .................................................................................................................... 6 
1.1. 
STUDY OVERVIEW .......................................................................................................... 6 
1.2. 
SCHEDULE OF ASSESSMENTS ..................................................................................... 8 
2. 
OBJECTIVES ......................................................................................................................... 11 
3. 
GENERAL STATISTICAL CONSIDERATIONS ............................................................. 12 
3.1. 
SAMPLE SIZE AND POWER ......................................................................................... 12 
3.2. 
RANDOMIZATION AND MASKING ........................................................................... 12 
3.3. 
HANDLING OF DATA .................................................................................................... 13 
3.3.1. Strata and Covariates ................................................................................................... 13 
3.3.2. Examination of Subject Subsets ................................................................................... 13 
3.3.3. Multiple Testing and Comparisons .............................................................................. 13 
3.3.4. Missing Data and Outliers ............................................................................................ 13 
3.3.5. Imputation of Incomplete Dates ................................................................................... 13 
3.3.6. Definitions and Terminology ........................................................................................ 14 
3.3.7. Presentations by Study Visit ......................................................................................... 16 
3.4. 
TIMING OF ANALYSES ................................................................................................. 17 
3.4.1. Interim Analysis ............................................................................................................ 17 
3.4.2. End of Open Label Analysis ......................................................................................... 17 
4. 
ANALYSIS POPULATIONS ................................................................................................ 17 
4.1. 
INTENT-TO-TREAT (ITT) POPULATION .................................................................. 17 
4.2. 
SAFETY POPULATION .................................................................................................. 17 
4.3. 
PER PROTOCOL (PP) POPULATION ......................................................................... 17 
5. 
STATISTICAL METHODS .................................................................................................. 18 


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5.1. 
SUBJECT DISPOSITION, DEMOGRAPHIC AND BASELINE 
CHARACTERISTICS ................................................................................................................... 18 
5.2. 
EFFICACY ANALYSIS ................................................................................................... 19 
5.2.1. Primary Efficacy Endpoint........................................................................................... 19 
5.2.2. Primary Efficacy Analysis ............................................................................................ 19 
5.2.3. Additional Analyses of the Primary Endpoint ............................................................ 20 
5.2.4. Secondary Efficacy Endpoints ..................................................................................... 20 
5.2.5. Secondary Efficacy Analysis ......................................................................................... 20 
5.2.6. Other Efficacy ................................................................................................................ 21 
5.2.7. Subset Analyses ............................................................................................................. 21 
5.2.8. Graphical Displays ........................................................................................................ 22 
5.2.9. Open-Label Extension ................................................................................................... 22 
5.3. 
SAFETY ............................................................................................................................. 23 
5.3.1. Adverse Events .............................................................................................................. 23 
5.3.2. Clinical Laboratory Assessments, Vital Signs, and Physical Examination Findings
 
24 
5.3.3. Other Safety Analyses ................................................................................................... 24 
5.3.4. Open-Label Extension Safety Analyses ....................................................................... 24 
6. 
CHANGES IN THE PROTOCOL-SPECIFIED ANALYSES ........................................... 25 
7. 
PROGRAMMING CONVENTIONS ................................................................................... 26 
8. 
PROPOSED TABLES, LISTINGS, AND FIGURES ......................................................... 28 
8.1. 
END OF DOUBLE-BLIND TREATMENT PERIOD ANALYSIS .............................. 28 
8.2. 
END OF OPEN LABEL EXTENSION PERIOD ANALYSIS ...................................... 34 
 


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GLOSSARY OF ABBREVIATIONS 
Abbreviation 
Term 
AA 
Alopecia Areata 
AE 
Adverse Event 
AIA-PRO 
Alopecia Impact Assessment-Patient Reported Outcome 
ALODEX 
Alopecia Density and Extent Score 
BID 
Twice daily 
CBC 
Complete Blood Count 
CI 
Confidence Interval 
ClinRO 
Clinician Reported Outcome 
CRF 
Case Report Form 
CR 
Clinician Rating 
DB 
Double-Blind 
DLQI 
Dermatology Life Quality Index 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
ICF 
Informed Consent Form 
ITT 
Intent-to-Treat 
LOCF 
Last Observation Carried Forward 
LS Mean 
Least Squares Mean 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed Effect for Repeated Measures 
mL 
Milliliter 
msec 
Millisecond 
OLE 
Open Label Extension 
PE 
Physical Examination 
PhGIC 
Physician Global Impression of Change 
PhGIS 
Physicians Global Impression of Severity 
PP 
Per- protocol 
PRO 
Patient-Reported Outcome 
SAE 
Serious Adverse Event 
SALT 
Severity of Alopecia Tool 
SAP 
Statistical Analysis Plan 
Scalp-ClinRO 
Item 1 and Item 2 Scalp-ClinRO for AAP1 
Scalp-PRO 
Item 1 and Item 2 Scalp-PRO for AAP2 
SGIC 
Subject Global Impression of Change 
SGIS 
Subject Global Impression of Severity 
SGITS 
Subject Global Impression of Treatment Satisfaction 
TEAE 
Treatment Emergent Adverse Events 
UPT 
Urine Pregnancy Test 
WHO 
World Health Organization 
WOCBP 
Women of Child Bearing Potential 
1This assessment is named Alopecia Scalp Appearance Assessment for Patchy AA-Clinician Rating in the protocol. 
2This assessment is named Alopecia Scalp Appearance Assessment for Patchy AA-Subject Rating in the protocol. 
 


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1. 
INTRODUCTION 
This document describes the statistical methods and data presentations to be used in the summary 
and analysis of data from Protocol ATI-50002-AA-201. Background information is provided for 
the overall study design and objectives.  The reader is referred to the study protocol and case report 
forms (CRFs) for details of study conduct and data collection.  
The scope of this document excludes the analysis of biomarker data being collected at specific sites 
and the evaluation of the psychometric properties of the newly developed patient-reported (PRO) 
and clinician-reported outcome (ClinRO) questionnaires. 
1.1. 
STUDY OVERVIEW 
This Phase 2, multicenter, randomized study is designed to evaluate the safety, tolerability and 
efficacy of ATI-50002 Topical Solution in subjects with stable patchy alopecia areata (AA). 
Subjects will be required to have a clinical diagnosis of AA with at least 15% up to 95% total scalp 
hair loss for a duration of at least 6 months up to and including 12 years. 
 
This study has a double-blind period and an open-label extension period. 
 
Double-blind (DB) Period:   
A total of 120 subjects will be randomized in a 1:1:1 ratio: 
 
Vehicle Topical Solution BID for 24 weeks (6 months) 
 
ATI-50002 Topical Solution, 0.12%, BID for 24 weeks (6 months) 
 
ATI-50002 Topical Solution, 0.46%, BID for 24 weeks (6 months) 
 
During the screening period, subjects will be assessed for eligibility into the study. Subjects will 
apply up to 4 mL of study medication to the entire scalp or patchy areas with a ½” margin twice a 
day for 24 weeks. Assessment of response to treatment will be performed at Week 4 (Visit 5), 
Week 8 (Visit 6), Week 12 (Visit 7), Week 16 (Visit 8), Week 20 (Visit 9), Week 24 (Visit 10), and 
post-treatment Week 28 (Visit 11). Safety and tolerability will be evaluated at each study visit by 
assessment of adverse events and vital signs, and at select visits, ECGs and clinical laboratory tests 
will be completed. The primary analysis will be conducted after all subjects complete Visit 10 or 
Visit 11 of the double-blind period.  
 
Subjects who complete Visit 10 or Visit 11 (Week 24 or 28) will be eligible to enter a 28 week 
OLE. Subjects who decline or are not eligible for the OLE should be seen for the Visit 11 (Post-
treatment) assessments.  
 
Open-Label Extension (OLE):  
In the OLE, safety, tolerability and efficacy will be assessed. All subjects enrolled in the OLE will 
apply ATI-50002 Topical Solution, 0.46% to the entire scalp or patchy areas with a ½” margin, 
twice daily for 24 weeks (6 months). In addition, subjects with eyebrow loss may apply study 


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medication to the entire eyebrow(s) twice daily for 24 weeks. Subjects will be followed for safety, 
tolerability and efficacy as detailed in Section 1.2 Schedule of Assessments. Subjects who entered 
the OLE and for administrative reasons had a gap of > 30 days between completion of Visit 10 or 
Visit 11 and entry into the open-label should return for the OLE Visit 1 and have the procedures 
detailed in the Schedule of Assessments. 


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1.2. 
SCHEDULE OF ASSESSMENTS 
Double-Blind Treatment Period 
Screening 
Baseline 
Treatment 
Post-
Treatment 
 
Visit 1 
Visit 2 
Visit 
3 
Visit 
4 
Visit 
5 
Visit 
6 
Visit 
7 
Visit 
8 
Visit 
9 
Visit 
10 
Visit 11 
Week  
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
Treatment Day 
-30 to 0 
1 
8 
15 
29 
57 
85 
113 
141 
169 
197 
Treatment window (days) 
N/A 
N/A 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Informed consent/assent1 
X 
 
 
 
 
 
 
 
 
X14 
X14 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Physical exam2 
X 
 
 
 
 
 
 
 
 
X 
 
Demographics & medical history 
X 
 
 
 
 
 
 
 
 
 
 
Alopecia Areata History 
X 
 
 
 
 
 
 
 
 
 
 
Vital Signs3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical CBC, Chemistry, Virology, Serum Pregnancy, Urinalysis4 
X4 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test5 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
SALT Score (prior to ALODEX)6 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
ALODEX Score (after SALT)7 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Target Scalp Patch Identification8 
 
X 
 
 
 
 
 
 
 
 
 
Assessment of hair quality9 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Scalp-ClinRO 
All Patches, Target Patch10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Scalp-PRO 
All Patches, Target Patch10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Physician Global Impression of Severity (PhGIS) 10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Physician Global Impression of Change (PhGIC) 
 
 
 
 
 
 
 
 
 
X 
 
Subject Global Impression of Severity (PhGIS) 10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Subject Global Impression of Change (PhGIC) 
 
 
 
 
 
 
 
 
 
X 
 
Subject Global Impression Treatment Satisfaction (SGITS) 
 
 
 
 
 
 
X 
 
 
X 
 
DLQI10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Alopecia Impact Assessment-Patient Reported Outcome (AIA-PRO) 10 
 
X 
 
 
X 
 
X 
 
 
X 
 
Photography (complete scale and target patch) 10 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Subject Randomization 
 
X 
 
 
 
 
 
 
 
 
 
Subject instructions11 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Dispense collect, weigh study medications12 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
In office study medication applications13 
 
X 
 
 
 
 
 
 
 
 
 
Concomitant therapies 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Open-Label Extension 
Open-Label Treatment 
Post 
Treatment 
OLE Visit 1 
  
OLE 
Visit 2 
OLE 
Visit 3 
OLE 
Visit 4 
OLE  
Visit 5 
OLE  
Visit 6 
Week  
OLE Visit 1 occurs 
at Visit 10 or 11 
Visit 11 (Week 28) was: 
2 
4 
12 
24 
28 
Treatment Day 
≤ 30 Days 
>30 Days 
15 
29 
85 
169 
197 
Treatment window (days) 
NA 
NA 
NA 
±3 
±3 
±7 
±7 
±7 
Informed consent/assent1 
X 
X 
X 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
X 
 
 
 
 
 
Physical exam2 
 
 
X 
 
 
 
 
X 
Medical History Update 
 
 
X 
 
 
 
 
 
Vital Signs3 
 
X 
X 
X 
X 
X 
X 
X 
Clinical CBC, Chemistry, Virology, Serum Pregnancy, Urinalysis4 
 
 
X 
X 
X 
X 
X 
X 
Urine pregnancy test5 
 
X 
X 
X 
X 
X 
X 
X 
ECG 
 
 
 
 
 
 
 
X 
SALT Score (prior to ALODEX)6 
 
X15 
X 
 
X 
X 
X 
X 
ALODEX Score (after SALT)7 
 
X15 
X 
 
X 
X 
X 
X 
Scalp-ClinRO (All Patches, Target Patch) 
 
 
 
 
X 
X 
X 
Scalp-PRO (All Patches, Target Patch) 
 
 
 
 
X 
X 
X 
SGITS 
 

 
 
 
X 
 
Photography (complete scalp and target patch) 
 
X15  
 
X 
X 
X 
X 
Subject Instructions11 
X 
X 
X 
X 
X 
X 
 
Dispense and weigh study medication12 
X 
X 
X 
X 
X 
X 
(Weigh 
only) 
 
Collect study medication, assess compliance 
 
 
X 
X 
X 
X 
 
Concomitant therapies 
 
X 
X 
X 
X 
X 
X 
Adverse events 
 
X 
X 
X 
X 
X 
X 
 
1 A written, signed ICF/ assent must be obtained from each subject prior to performing any study related procedure (i.e., prior to performing vital signs, standardized 
photography, biopsies, clinical laboratory sampling or urine pregnancy tests.)  An OLE ICF must be obtained prior to performing any OLE assessments. 
2 A physical exam includes: general appearance, extremities, examination of head, eyes, ears, nose and throat, respiratory, cardiovascular, abdominal, neurological, 
musculoskeletal, lymphatic and skin assessment.  
3 Vital signs include: oral or ear temperature, blood pressure, heart rate, respiration rate (height and weight at baseline only).  
4 Clinical laboratory sampling include: CBC, Chemistry with lipids, Urinalysis.  Quantiferon Gold, HIV, Hepatitis B and C, and Serum Pregnancy  
5 UPT must be performed in WOCBP prior to randomization at Baseline (Visit 2) and must be negative for the subject to continue in the study.  UPTs in WOCBP must also 
be obtained at Visits 5, 6, 7, 8, 9, 10, 11 and if applicable, OLE Visit 1, and OLE Visit 2-6.  WOCBP must have a negative serum pregnancy test at Screening (Visit 1) and a 
negative UPT at baseline (Visit 2) prior to randomization. WOCBP must have a negative UPT prior to continuation into the OLE.  


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6 SALT score must be determined prior to ALODEX using device provided.  At Baseline (Visit 2), SALT score should be determined prior to application of study medication.  
7 ALODEX score determined after SALT score using device provided. At Baseline (Visit 2), ALODEX score should be determined prior to application of study medication.  
8 The subject will be instructed to identify the most bothersome patchy area- this will be the Target Patch. At Baseline (Visit 2), the Target Patch should be identified prior to 
application of study medication.  
9 The investigator will assess active hair loss through the hair pull test and the presence of exclamation point hairs.  At Baseline (Visit 2), the assessment should be determined 
prior to application of study medication.  
10 At Baseline (Visit 2), study assessments must be performed prior to application of study medication.  
11 The study staff must instruct the subject to apply study medication according to the instructions in APPENDIX 1, 2 and 3.  
12 The study staff must weigh the study medication bottle(s) with cap prior to dispensing to the subject and after the study medication bottles are returned to the investigational 
site.  Staff should review the usage based on the weight of the bottle and counsel the subject as necessary. 
13 At Baseline (Visit 2), the first application of study medication should be performed by the subject under the supervision of the study staff and the subject should be 
observed for 20 minutes after the initial application. 
14At Week 24 (Visit 10) or Week 28 (Visit 11), the subject may be given the option to move into the OLE treatment.  
 
If the subject declines the OLE, Visit 11 (Post-treatment) will be the last double-blind study visit.   
 
If the subject chooses to continue into the OLE, she/he must sign an OLE ICF, complete Visit 10 or Visit 11 as appropriate and OLE Visit 1, prior to being dispensed 
openlabel drug and receiving study medication application instructions. The subject will be scheduled for OLE Visit 2.    
 
If the subject enrolls in open-label treatment within 30 days of completion of Week 24 (Visit 10) or Week 28 (Visit 11), OLE Visit 1 will be conducted to obtain 
consent/assent and perform the procedures in the Schedule of Assessments. This will be considered the official date that the subject initiated OLE treatment.   
 
If the subject enrolls in open-label treatment > 30 days after completion of Week 28, OLE Visit 1 will be conducted to obtain consent/ assent, and complete the 
procedures detailed in the Scheduled of Events. This will be considered the official date that the subject initiated OLE treatment and the scheduling of subsequent 
visits will be based on this date.   
15 SALT, ALODEX and Photography is performed at OLE Visit 1 (if Week 28 is < 30 days) only if there is a significant change from the last double-blind study visit. 
 


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2. 
OBJECTIVES 
Primary Objective: 
 
The primary objective of this study is to assess the safety, tolerability and efficacy of ATI-50002 
Topical Solution, 0.46% and 0.12% compared to vehicle in subjects with stable patchy alopecia 
areata (AA). 
 
Efficacy assessments include the following scores and/or scales: 
 
 
Severity Alopecia Tool (SALT) Score 
 
Alopecia Density and Extent Score (ALODEX) 
 
Assessment of Hair Qual 
 
Item 1 and Item 2 Scalp-ClinRO for AAP (Scalp-ClinRO), referred to as Alopecia Scalp 
Appearance Assessment for Patchy AA – Clinician Rating in protocol for target patch and 
entire scalp.  
 
Item 1 and Item 2 Scalp-PRO for AAP (Scalp-PRO), referred to as Alopecia Scalp Appearance 
Assessment for Patchy AA – Subject Rating in protocol for target patch and entire scalp.  
 
Physician Global Impression of Severity (PhGIS) 
 
Subject Global Impression of Severity (SGIS)  
 
Alopecia Impact Assessment – Patient Reported Outcome (AIA-PRO) 
 
Subject Global Impression of Treatment Satisfaction (SGITS) 
 
Dermatology Life Quality Index (DLQI) total score 
 
Physician Global Impression of Change (PhGIC) 
 
Subject Global Impression of Change (SGIC) 
 
Safety assessments include: 
 
Adverse events  
 
Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) 
 
Vital sign measurements (systolic and diastolic blood pressure, respiration rate, heart rate, 
and temperature) 
 
Electrocardiograms 
 
Secondary Objective: 
 
The secondary objectives are as follows:  
 
To evaluate the psychometric performance of the key clinical outcome assessments 
questionnaires with respect to reliability, construct-related validity, and sensitivity to 
change  
 
To generate score interpretation estimates for the clinical outcome assessments to guide the 
definition of responders in pivotal trials  
 


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The secondary objectives are not within the scope of this SAP.  
Exploratory Objectives (Select Sites Only): At select clinical sites, to explore the effects of ATI-
50002 induced Janus kinase (JAK) 1/3 inhibition on the ALADIN scores, peribulbar infiltrate and 
other inflammatory biomarkers.  
The exploratory objectives are not within the scope of this SAP.  
 Long-term Objective To assess the safety, tolerability and efficacy of ATI-50002 Topical 
Solution, 0.46% in subjects with stable patchy alopecia areata.  
This objective will be assessed at the end of the Open Label Extension period. 
3. 
GENERAL STATISTICAL CONSIDERATIONS 
3.1. 
SAMPLE SIZE AND POWER 
The planned sample size is 120 subjects.  Since this is the first multicenter study evaluating the effect 
of ATI-50002 Topical Solution in subjects with stable patchy alopecia areata, the sample size was 
based upon feasibility issues rather than on a formal power calculation.    However, data from 120 
subjects (40 per group), utilizing LOCF for missing data, provides 80% power to detect a 24-point 
difference in percent change from baseline in SALT score between any two treatment groups.  This 
power computation was based upon the assumed standard deviation of 38%.  Data from a previous 
study NCT02197455 showed that the standard deviation in percent change from baseline in the 
SALT score is 30.3%.  The 38% standard deviation assumption used for this power computation was 
chosen to account for the increase in variance due to the lower baseline SALT entry criteria for this 
study as compared to NCT02197455. 
 
3.2. 
RANDOMIZATION AND MASKING 
 
Prior to the start of the study, Aclaris Therapeutics, Inc. or a designated third party will generate a 
list of randomization numbers that shall be transmitted to the assigned clinical packaging 
organization for study medication labeling.  The randomization list will be stored with access limited 
to designated personnel for study medication labeling.  The randomization list will be made available, 
as appropriate, to unblind the database.  
 
In the double-blind period, subjects will be assigned to 1 of the 3 treatment groups in a random 
manner and at a 1:1:1 ratio. At Baseline (Visit 2), an investigational center staff member will assign 
study medication to eligible subjects by selecting an appropriate Subject Kit.  The staff member must 
select Subject Kits in chronological sequence and in an ascending numerical order starting with the 
lowest available Subject Kit number.  No Subject Kit number may be omitted or reused.  The Subject 
Kit number is the randomization number.    
  
The investigational staff member randomizing the subject will enter the subject identifier, subject 
initials, and date randomized on both parts of the Subject Kit label, remove the tear-off part, attach 


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it to the subject’s study medication eCRF label page and record the Subject Kit number in the 
subject’s eCRF.  
 
3.3. 
HANDLING OF DATA 
3.3.1. 
Strata and Covariates 
The baseline SALT score group (<50, >=50) will be used a stratum in the planned primary efficacy 
models. The strata will not be used in the subset analyses. 
3.3.2. 
Examination of Subject Subsets 
The baseline SALT score group (< 50, >=50) and the subjects who treat the whole scalp will be 
used for subset analyses. The details of the subset analyses are given in the statistical analysis 
section.  
3.3.3. 
Multiple Testing and Comparisons  
There are no planned adjustments for multiple comparisons. 
3.3.4. 
Missing Data and Outliers 
For missing clinical assessments, the method of last observation carried forward (LOCF) will be 
used to impute values. The last non-missing value prior to the missing assessment will replace the 
missing values. For subjects who terminate early, missing assessment after the date of early 
termination will be replaced by the LOCF method. 
 
3.3.5. 
Imputation of Incomplete Dates 
A missing date is one in which the day, month or year are all unknown. For adverse events, if a 
date is missing entirely then the date will be set to equal Day 1.  
An incomplete date is any date for which either the day, month or year is unknown, but all three 
fields are not unknown.  An incomplete date occurs when the exact date an event occurred or ended 
cannot be obtained from a subject.  For many of the analyses, a complete date is necessary in order 
to determine if the event should be included in the analysis (i.e., if the event is treatment-emergent) 
or to establish the duration of an event.  In such cases, incomplete dates will be imputed. 
To minimize bias, the project statistician will impute dates in a systematic, but reasonable manner. 
If the month/year is the same as the Day 1 month/year then the date will be set to the date of Day 1.  
In other cases, missing days will be imputed as the day component of Day 1; missing months/years 
will be imputed as the month/year of Day 1. For nonexistent dates occurring at the end of a month 
created by this imputation method, the first date of the next month will be used (e.g. Day 1 = 
31JAN2017, incomplete date = XXFEB2017 -> imputed date = 01MAR2017). 


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3.3.6. 
Definitions and Terminology  
 
Day 1 (DB) 
Day 1 (DB) is defined as the date of the initial study medication application as reported on the 
study medication usage page of the CRF. 
 
Day 1 (OLE) 
Day 1(OLE) is defined as the date of the Visit 10 assessment for all subjects entering the OLE 
period.  
 
Study Day  
Study Day is defined relative to Day 1(DB).  Thus, the study day of an event is calculated as: 
Study Day = ((event date – date of Day 1(DB)) + 1) for dates on or after Day 1(DB)  
Study Day = (event date – date of Day 1) for dates prior to Day 1(DB) 
Period Day  
Period Day is defined separately for the DB and OLE periods. Period day will be relative to the 
defined Day 1 of each period.   
 
Study Visit 
Study Visit is the nominal visit as recorded on the CRF. 
Days on Study 
Days on Study is calculated as: study discontinuation date - informed consent date + 1 
 
Last Dose of Study Medication 
Last Dose of Study Medication is defined as the last date that the subject applied study medication 
as determined by last date of recorded on the study medication usage page of the CRF. 
Study Medication Exposure (days) in DB 
Study drug exposure is defined as the (date of last DB dose – date of first dose + 1).   
 
Dose Interruptions 
Dose interruption is defined as 2 or more consecutive days where ‘None’ was checked for the 
number of applications per day field on the study medication page of CRF.  
Missed Dose 
A missed dose is defined as a single day where ‘None’ was checked for the number of applications 
per day field on the study medication page of CRF.  
Study medication compliance (%) based on number of applications 
The compliance with the dosing regimen will be calculated based on the subject-specific 
application regimen as, [(study medication exposure days - number of days with less than the 
subject-specific expected number of applications) / (study medication exposure days)] x 100.  


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Age 
The age of a subject is defined as the number of whole calendar years from the subject’s date of 
birth to the date of informed consent. 
Baseline Value 
For purposes of analysis, the baseline value is defined as the last non-missing value obtained prior 
to initiation of study medication. 
 
Change from Baseline  
Change from Baseline for a given endpoint is defined as the value at the analysis visit minus the 
baseline value. 
Duration of alopecia 
Date of Informed Consent minus the original onset date of alopecia as reported on the History of 
Alopecia page of eCRF.   
Duration of current episode of patchy alopecia 
Date of Informed Consent minus the onset date of current episode of Patchy Alopecia as reported 
on the History of Alopecia page of eCRF.   
Prior Medications 
Prior medications are those medications taken prior to the initiation of study medication, regardless 
of whether it continues into the blinded treatment period. 
 
Concomitant Medications 
Concomitant medications are those medications taken on or after the initiation of study medication.  
This definition includes medications started prior to the initiation of study medication but 
continuing concomitantly with the study medication.   
 
DLQI Total Score - The scoring of each question is as follows:  
Very much=scored 3, A lot=scored 2, A little= scored 1, Not at all= scored 0, Not relevant=scored 
0, Question 7, ‘prevented work or studying’=scored 3.  
The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a 
minimum of 0. The higher the score, the more quality of life is impaired. 
 
Adverse Event (AE) 
An AE is any untoward medical occurrence in a subject administered a study medication(s) 
and which does not necessarily have a causal relationship with the study medication. An AE 
can therefore be any unfavorable and unintended sign or symptom associated with the use of a 
study medication (including an abnormal laboratory finding), whether related to the study 
medication. Thus, any new, clinically significant worsening of an existing sign, symptom or 
disease, should be considered an AE. Every new episode or clinically significant worsening of 
a chronic condition (e.g., headaches, seasonal allergies, depression, or hypertension) should be 
reported as a separate AE, even if the condition is reported in the subject’s medical history.  
 


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Treatment-Emergent Adverse Event (TEAE) 
For the interim analysis of the DB treatment period, any recorded AE that occurs on or after the 
initiation of study medication and within 31 days after the date of Visit 10 or after the date of last 
DB dose of study medication will be considered treatment-emergent.  For the OLE period analysis, 
an AE that occurs on or after the initiation of OLE study medication and within 31 days after the 
date of last dose of study medication will be considered treatment-emergent. 
 
Treatment-emergent Laboratory Abnormalities 
A treatment-emergent laboratory abnormality is defined as a result in which the baseline value is 
within normal laboratory limits and the post-baseline value is outside normal laboratory limits. If 
the relevant baseline assessment is missing, then any post-baseline value outside normal laboratory 
limits is treatment-emergent. 
   
3.3.7. 
Presentations by Study Visit 
Results from efficacy assessments and safety will be summarized by study visit and treatment 
group. For the DB period, all assessments will be assigned to an analysis visit window using the 
study day ranges described in Table 1. All study days up to and including Day 1 (DB) are 
considered the baseline eligible analysis visit window. The last non-missing assessment in the 
baseline analysis visit window will be used for the baseline summary presentations. If assessments 
are collected multiple times within a given analysis visit window, the result closest to the target 
study day, regardless of whether scheduled or unscheduled, will be used for summary 
presentations. If two measurements have the same distance to the target study day, the first 
assessment will be used in the summary presentations.  All assessments will be presented in the 
listings.  
Table 1: Visit Windows 
Nominal Visit 
Target Study Day 
Analysis Visit 
Study Day Range 
Screening 
-30 to -1 
Baseline 
<=1 
Day 1 
1 
Week 1 
8 
Week 1 
[2 – 11]  
Week 2 
15 
Week 2 
[12 – 22] 
Week 4 
29 
Week 4 
[23 – 42] 
Week 8 
57 
Week 8 
[43 – 70] 
Week 12 
85 
Week 12 
[71 – 98] 
Week 16 
113 
Week 16 
[99 – 126] 
Week 20 
141 
Week 20 
[127 – 154] 
Week 24 
169 
Week 24 
[155 to 182] 
 
For the OLE, the analyses will be based on the nominal study visit as reported on the CRF.  
 


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3.4. 
TIMING OF ANALYSES 
3.4.1. 
Interim Analysis 
When all subjects have completed the blinded treatment period or terminated early from the 
blinded treatment period and data have been cleaned and forwarded for analysis, the study will be 
unblinded and the safety and efficacy analysis will be performed according to this SAP.  See 
Section 8.1. for the list of proposed summary table and figures and data listings for the End of 
Double-Blind Treatment Period analysis. 
3.4.2. 
End of Open Label Analysis 
A final analysis will also be performed at the end of the open-label extension period.  See Section 
8.2. for the list of proposed summary table and figures and data listings for the End of Open Label 
Period analysis. 
 
4. 
ANALYSIS POPULATIONS 
The populations for analysis will include the intent-to-treat population (ITT), the safety population 
(SAF), and the per protocol (PP) population. 
4.1. 
INTENT-TO-TREAT (ITT) POPULATION 
The ITT population is the population of all subjects who are randomized into a treatment group. 
Subjects in this population will be analyzed according to the treatment group to which they were 
randomized. The ITT population will be used for all efficacy analyses.  
4.2. 
SAFETY POPULATION  
 
The Safety population is defined as all randomized subjects who applied at least 1 application of 
study medication. Subjects in this population will be analyzed according to the treatment which 
they receive. All safety analyses will be based on this population. 
4.3. 
PER PROTOCOL (PP) POPULATION 
The Per-Protocol (PP) population is defined as all subjects who are randomized and do not have 
any major protocol violations. Major protocol violations that will lead to exclusion from the PP are 
defined as: 
1. Inclusion or Exclusion criteria not met 
2. Concomitant medications taken during the study that interfere with efficacy 
3. Did not apply at least 75% of study medication 


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4. Did not complete Week 24 (Visit 10). 
This population will be used for supportive analyses of key efficacy analyses.  
5. 
STATISTICAL METHODS 
Descriptive statistical methods will also be used to summarize the data from this study, with 
hypothesis testing performed for the primary and key secondary efficacy endpoints.  Unless stated 
otherwise, the term “descriptive statistics” refers to number of subjects, mean, median, standard 
deviation, minimum, and maximum for continuous data, and frequencies and percentages for 
categorical data.  For categorical variables, the denominator of percentages will be the number of 
subjects in the treatment group, except for those collected by study visit and/or scheduled time 
point, in which case the denominator of percentages will be the number of subjects with a non-
missing value at the visit and/or the scheduled time point. If a different denominator is used, this 
will be identified in the summary table.  
All data collected during the study will be included in data listings.  Unless otherwise noted, the 
data will be sorted first by treatment group, subject number, and then by date within each subject 
number. Assessments indicated as ‘Not Done’ will not be includes in the listings. 
The term ‘treatment group’ refers to ATI-50002 active groups and matching Vehicle group. 
All statistical testing will be two-sided and will be performed using a significance (alpha) level of 
0.05 unless otherwise stated.  P-values will be presented to three decimal places.  For the efficacy 
endpoints, the ATI-50002 treatment groups will be tested versus vehicle via statistical inference.   
The statistical analyses will be conducted with the SAS® software package version 9.4 or higher.  
All analyses will be subject to formal verification procedures. Specifically, results will be 
independently verified by a second programmer/statistician or independently hand-checked prior to 
issuance of the draft statistical report. All documents will be reviewed by the lead statistician to 
ensure accuracy and consistency. 
5.1. 
SUBJECT DISPOSITION, DEMOGRAPHIC AND BASELINE 
CHARACTERISTICS  
Subject disposition will be presented for all subjects in the ITT population. The number of subjects 
who completed the study or early terminated from the study during the blinded treatment period 
will be provided. The reasons for early termination will be presented by treatment group. 
Additionally, the number of weeks on study will be summarized for all treated subjects.  
Demographic data, including age, gender, race, ethnicity, and Fitzpatrick skin type, and screening 
weight (kg) and height(cm) will be summarized using descriptive statistics by treatment group. 
This information will be reviewed for baseline differences, but no statistical testing will be 
performed. 


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Baseline characteristics, including duration of alopecia, duration of current episode of patchy 
alopecia (continuous and dichotomized (< 2 years, >= 2 years), baseline hair pull test results 
(dislodged hairs and broken hairs), baseline SALT score group (<50%, >50%) and baseline Scalp-
ClinRO and Scalp-PRO will be reported.   
Alopecia treatment history will be summarized. The count and percent of subjects using the 
therapies pre-specified on the History of Alopecia CRF page will be reported.  
Medical history will be summarized using the pre-specified CRF body system categories. The 
count and percent of subjects reporting a condition in the body system will be reported.  
Findings from the baseline physical examination (PE) will also be summarized using the pre-
specified body system categories and include reporting of abnormal not clinically significant and 
abnormal clinically significant.  
Prior and concomitant medications will be coded using the World Health Organization (WHO) 
Drug Dictionary (version WHO-DD – March 2019) for the entire period of the study. Prior and 
concomitant medications will be summarized in tables and may be presented in data listings.   
Study drug exposure and compliance will be summarized by treatment. The study drug duration 
along with summaries of missed doses, dose reductions, and treatment compliance will be reported.   
5.2. 
EFFICACY ANALYSIS 
 
5.2.1. 
Primary Efficacy Endpoint 
The primary efficacy variable will be the mean percent change from baseline in the SALT score at 
Week 24 (Visit 10). 
 
5.2.2. 
Primary Efficacy Analysis 
Descriptive statistics for the SALT score, change, and percent change from baseline will be 
presented for each scheduled analysis visit. Percent change from baseline in SALT over time up to 
Week 24 will be analyzed using a mixed effect for repeated measures (MMRM) model. This 
primary analysis will utilize the score with imputation for LOCF and will be based on the ITT 
population. The model will include fixed effect terms for treatment, study visit, baseline SALT 
score group (<50, >=50), and treatment by SALT group interaction. Within-subject variability will 
be modeled using a compound symmetry covariance structure. The least squares mean (LS Mean) 
percent change from baseline in the SALT score at each visit, estimated from the MMRM model, 
with the estimated standard error and 95% confidence interval (CI), will be presented in tabular and 
graphic format. The difference in the adjusted means between treatment groups and the associated 
95% CI of the difference will be provided.  
 


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5.2.3. 
Additional Analyses of the Primary Endpoint 
The statistical methods for the main analysis will be repeated using the PP population. The analysis 
will also be performed using the observed data without imputation for missing in both the ITT 
population and the PP population. 
 
Another exploratory MMRM analysis for the primary endpoint will be performed with factors for 
the duration of current episode of patchy alopecia (< 2 years, >= 2 years) and the treatment by 
duration of episode interaction replacing the baseline SALT score group and treatment by SALT 
group interaction factors. This analysis will be performed in both the ITT population and the PP 
population using data with LOCF imputation.   
 
5.2.4. 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints include:  
 
Mean percent change from baseline in the ALODEX score at Week 24 (Visit 10), also 
described as mean percent regrowth, 
 
Mean change from baseline in SALT score at Week 24 (Visit 10) 
 
Mean change from baseline in ALODEX score at Week 24 (Visit 10)  
 
Proportion of subjects in each treatment arm achieving ≥ 50% hair regrowth compared with 
baseline using a separate model for SALT and for ALODEX scores 
 
Change from baseline in the Scalp-PRO at Week 24 (Visit 10)  
 
Change from baseline in the Scalp-ClinRO at Week 24 (Visit 10) 
 
Change from baseline in the PhGIS of Patchy AA at Week 24 (Visit 10) 
 
Change from baseline in the SGIS of Patchy AA at Week 24 (Visit 10) 
 
Change from baseline in the subject reported AIA-PRO at Week 24 (Visit 10) 
 
SGITS at Week 24 (Visit 10) 
 
Change in DLQI total score between Baseline and Week 24 (Visit 10) 
 
PhGIC at Week 24 (Visit 10) 
 
SGIC at Week 24 (Visit 10) 
 
5.2.5. 
Secondary Efficacy Analysis 
Descriptive statistics will be presented for all secondary efficacy endpoints.  
The mean percent change from baseline in the ALODEX score (percent regrowth); the mean 
change from baseline in SALT and the mean change from baseline in ALODEX will be analyzed 
using the methods planned for the primary efficacy analysis.  The calculated DLQI total score 
ranges from 0 to 30. This mean change from baseline in DLQI will also utilize the MMRM 
analysis as planned for the primary efficacy analysis. 
Responder-type analyses are planned based on the SALT, ALODEX, Scalp-ClinRO, and Scalp-
PRO. The responder definitions include:  


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 
The proportion of subjects achieving a ≥ 50% hair regrowth compared with baseline for SALT 
and for ALODEX scores  
 
Proportion of subjects achieving an absolute SALT score <= 10 
 
Proportion of subjects with >= 2-point improvement in Scalp-ClinRO for the Target Area 
 
Proportion of subjects with >= 2-point improvement in Scalp-PRO for the Target Area 
 
Proportion of subjects with >= 1-point improvement in Scalp-ClinRO for the entire scalp 
 
Proportion of subjects with >= 1-point improvement in Scalp-PRO for the entire scalp 
The observed proportion of responders and associated 95% CI will be presented. Adjusted rates 
and 95% CI will be obtained from a logistic regression model with factors for treatment and 
baseline SALT score group.  The p-value for the overall global test that = 0 for each factor will be 
presented. The adjusted odds ratios (95% CI) for being a responder (active/vehicle) will be 
presented along with the associated p-value.   
The questionnaires Scalp-PRO, Scalp-ClinRO, PhGIS, and SGIS are collected on a 1-5 scale. The 
frequency of responses for each value will be reported by visit and treatment group. Additionally, 
change status will be categorized as “Better by x points” when the score decreases from baseline by 
x points, and as “Worse by x points” when the score increases by x points. For these scales, a 
stratified Wilcoxon rank sum test will be used at each visit to obtain a p-value to compare the 
change status of each active treatment group to the vehicle.   
For SGITS, PhGIC, and SGIC, the frequency of responses will be summarized for each scheduled 
collection timepoint. A stratified Wilcoxon rank sum test will be used at each visit to obtain a p-
value to compare the results of each active treatment group to the vehicle. 
The AIA-PRO consists of 13 questions each rated on a scale of 1 to 10 and mean total score. The 
mean total score is taken as the average of the 13 items. If any of the items is missing the mean 
total score will not be calculated. Descriptive statistics for actual and change from baseline for the 
mean total score and each individual item will be presented.  
5.2.6. 
Other Efficacy 
Results from the hair pull test at scheduled visits will be summarized. The summary will show the 
shift relative to baseline in the categories of dislodged hairs and broken hairs at each post-baseline 
analysis visit.  
5.2.7. 
Subset Analyses 
Subgroups of Baseline SALT score group (< 50, >=50) 
The primary analysis of the percent change in SALT score over time, the analysis of percent 
change in ALODEX score over time, and all planned responder-type analyses will be repeated in 


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each subgroup.  For these analyses, the baseline SALT score group will be removed from the 
planned MMRM model and logistic regression model. 
Subgroup of subjects who applied Whole Scalp Treatment 
This subset will consist of all subjects who indicated on the End of Blinded Treatment page of the 
eCRF that the whole scalp is treated twice per day. The primary efficacy analysis of the percent 
change in SALT score will be repeated in this subset. 
5.2.8. 
Graphical Displays 
For SALT and ALODEX, the LS mean percent change and 95% CI will be plotted over time by 
treatment group. For the binary efficacy endpoint of proportion of subjects achieving >=50% hair 
regrowth relative to baseline based on the SALT and ALODEX scores, the percentage and 95% CI 
will be plotted over time by treatment group.  
5.2.9. 
Open-Label Extension 
For the open label extension period, efficacy will be evaluated based on the SALT, ALODEX, 
Scalp-ClinRO, Scalp-PRO, and SGITS. Descriptive summary statistics will be reported for the 
following: 
 
SALT score and change from baseline 
 
ALODEX Score and change from baseline 
 
Number (%) of subjects for each category of the Scalp-ClinRO (target patch and entre scalp)  
 
Number (%) of subjects for each category of the Scalp-PRO (target patch and entre scalp)  
 
Number (%) of subjects for each category of SGITS. 
Summaries will include changes from baseline (study day 1) and changes from the end of the DB 
study (Visit 10). All by visit summaries will utilize the normal study visit based on CRF collection. 
The efficacy summaries will be presented for the following subject groups based on the DB 
treatment assignments and the duration since end of DB period:  
 
Subjects who were randomized to Vehicle in the double-blind portion of the study 
 
Subjects who were randomized to ATI-50002 12% in the double-blind portion of the study 
who also entered the OLE less than 7 days from the end of their DB treatment period 
 
Subjects who were randomized to ATI-50002 12% in the double-blind portion of the study 
who also entered the OLE more than 7 days, but less than 60 days from the end of their DB 
treatment period 
 
Subjects who were randomized to ATI-50002 12% in the double-blind portion of the study 
who also entered the OLE at least 60 days from the end of their DB treatment period 
 
Subjects who were randomized to ATI-50002 46% in the double-blind portion of the study 
who also entered the OLE less than 7 days from the end of their DB treatment period 


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 
Subjects who were randomized to ATI-50002 46% in the double-blind portion of the study 
who also entered the OLE more than 7 days, but less than 60 days from the end of their DB 
treatment period 
 
Subjects who were randomized to ATI-50002 46% in the double-blind portion of the study 
who also entered the OLE at least 60 days from the end of their DB treatment period. 
5.3. 
SAFETY 
All safety analyses will be performed on the Safety Population. Values for all safety variables will 
be listed by subject and visit (as applicable). 
5.3.1. 
Adverse Events 
Adverse events will be mapped to a preferred term and system organ classification by Medical 
Dictionary for Regulatory Activities (MedDRA) version 22.0.  
An overall summary will be presented which includes the number of TEAEs and the number and 
percentage of subjects who experienced at least one TEAE.  This summary will also include: 
 
Any TEAE 
 
Any Serious TEAE 
 
Any Mild TEAEs 
 
Any Moderate TEAEs 
 
Any Severe TEAEs 
 
Any Related TEAEs 
 
Any TEAEs leading to discontinuation 
 
Any Related TEAEs leading to discontinuation 
Additional summaries of TEAEs will be provided showing the number and percentage of subjects 
who experienced at least one TEAE.  These summaries will be presented by system organ class 
(SOC), preferred term (PT) and maximum severity. If a participant reports the same PT multiple 
times within the same SOC, that PT will only be counted once within that SOC for that participant.  
As with the PT, if a participant reports multiple conditions within the same SOC, that SOC will 
only be counted once for that participant.  In the summary, SOC will be listed in ascending 
alphabetical order; PTs will be listed in order of descending frequency for all participants within 
each SOC.   
The occurrence of TEAEs related to study medication (possibly/probably) will be tabulated by 
SOC, PT and maximum severity. Serious adverse events (SAE) will be presented by system organ 
class (SOC), preferred term (PT) and maximum severity.  SAE related to study medication will 
also be presented by SOC and PT. 
All AEs reported will be listed by individual subject, showing both verbatim and preferred terms. 
All AEs reported with a start date prior to the initiation of study medication will be excluded from 
the TEAE tables but will be included in the listings.  
Missing onset dates will be imputed as previously outlined in Section 3.3.5 as required to 
determine TEAEs. 


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5.3.2. 
Clinical Laboratory Assessments, Vital Signs, and Physical Examination 
Findings 
Descriptive summaries of quantitative clinical laboratory results (hematology, chemistry, and 
urinalysis) and their change from baseline values will be presented by study visit and treatment 
group.  Observed values of categorical urinalysis data will be displayed with frequencies and 
percentages.  All laboratory data will be listed for individual subjects.  
 
Treatment-emergent abnormal laboratory assessments will be based on the lab provided normal 
ranges. If the baseline laboratory assessment is normal and shifts to Low or High post-baseline, 
then the laboratory value is considered a TE abnormal laboratory value. For each protocol specified 
lab test, the number and percent of subjects reporting a TE abnormal lab will be reported.    
 
All laboratory summaries will be limited to the tests specified in the protocol.   
 
Descriptive summaries of vital signs and their change from baseline will be presented by study visit 
and treatment group and all vital signs will be listed.  
 
Post-baseline PE findings will be listed. 
5.3.3. 
Other Safety Analyses 
ECG measurements will include heart rate, QT interval, Fredericia-corrected QT interval (QTcF), 
PR interval, and QRS interval.  Change from baseline will be summarized descriptively by 
treatment group at each scheduled evaluation and all ECG data will be listed. Proportion of 
subjects with abnormal ECG interpretations will be summarized at each study visit and by 
treatment group. Proportion of subjects who meet each of the following criteria from International 
Conference on Harmonization Guideline E14 “Clinical Evaluation of QT/QTc Interval 
Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs” (October 2005) for QT 
and corrected QT intervals will be summarized across treatment groups: 
 
QT or QTcF >450 msec 
 
QT or QTcF >480 msec 
 
QT or QTcF >500 msec 
 
QT or QTcF increases from baseline by ≥30 msec 
 
QT or QTcF increases from baseline by ≥60 msec 
5.3.4. 
Open-Label Extension Safety Analyses 
Adverse events, laboratory values, and vital signs will be used in the OLE period to assess safety. 
Results occurring in just the OLE period will be reported based on the same treatment groups used 
for reporting during the DB portion of the study. The same analyses planned for the DB period will 
be generated for the OLE.  Additionally, pooled AE displays will be developed.   For the pooled 
analysis, only AEs in the OLE would apply to the patients randomized to vehicle during the DB 


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portion of the study.  For patients randomized to ATI-502 during the DB portion, their complete 
AE profile for the entire study should be summarized in the pooled analysis. 
6. 
CHANGES IN THE PROTOCOL-SPECIFIED ANALYSES 
All analyses specified in the SAP are consistent with those specified in the protocol. Should any 
deviations from the analyses specified in the authorized statistical analysis plan arise, such 
deviations will be documented in the final clinical study report. 


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7. 
PROGRAMMING CONVENTIONS 
 
Page orientation, margins, and fonts: Summary tables, listings, and figures will appear in 
landscape orientation.  There should be a minimum of a 1” boundary on the upper (bound) 
edge, and a minimum of a 1.0” boundary on the remaining three edges.  Output should be 
printed in Courier New with a point size of 8.  Titles may be printed using a larger font (e.g., 
Arial point size 10). 
 
Identification of analysis population: Every summary table and figure should clearly specify 
the analysis population being summarized.  Listings will be prepared for all subjects. 
 
Group headers: In the summary tables, the group headers will identify the summary group and 
the sample size for the indicated analysis population.  Of note, the header’s sample size does 
not necessarily equal the number of subjects summarized within any given summary module; 
some subjects in the analysis population may have missing values and thus may not be 
summarized. 
 
Suppression of percentages corresponding to null categories: When count data are presented as 
category frequencies and corresponding percentages, the percent should be suppressed when 
the count is zero in order to draw attention to the non-zero counts. 
 
Presentation of sample sizes: Summary modules should indicate, in one way or another, the 
number of subjects contributing to the summary statistics presented in any given summary 
module.  As mentioned above, this may be less than the number of subjects in the analysis 
population due to missing data. 
 
In the quantitative modules describing continuous variables (and thus presenting sample 
size, means, and standard deviations), the sample size should be the number of non-
missing observations.   
 
For categorical variables that are presented in frequency tables, the module should present 
the total count in addition to the count in each category.  Percentages should be calculated 
using this total as the denominator, and the percentage corresponding to the sum itself (that 
is, 100%) should be presented to indicate clearly to a reviewer the method of calculation.   
 
Sorting: Listings will be sorted by treatment group, subject number and date, if applicable.   
 
General formatting rules: Rounding for all variables will occur only as the last step, 
immediately prior to presentation in listings, tables, and figures.  No intermediate rounding will 
be performed on derived variables.  The standard rounding practice of rounding numbers 
ending in 0-4 down and numbers ending in 5-9 up will be employed.   
 
Numerical Values: The presentation of numerical values will adhere to the following 
guidelines:  
 
Raw measurements will be reported to the number of significant digits as captured 
electronically or on the CRFs.   
 
Standard deviations will be reported to two decimal places beyond the number of decimal 
places the original parameter is presented. 


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 
Means will be reported to one decimal place beyond the number of significant digits as the 
parameter.  
 
Calculated percentages will be reported to one decimal place. 
 
Dates will be formatted as DDMMMYYYY.  Partial dates will be presented on data listings as 
recorded on CRFs. 
 
Time will be presented according to the 24-hour clock (HH:MM). 


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8. 
PROPOSED TABLES, LISTINGS, AND FIGURES 
8.1. 
END OF DOUBLE-BLIND TREATMENT PERIOD ANALYSIS 
Section 14.1 Accountability and Baseline Characteristics 
1. Table 14.1.1 Subject Disposition and Reasons for Early Termination, ITT Population 
2. Table 14.1.2 Primary Protocol Violations, ITT Population 
3. Table 14.1.3 Analysis Populations, ITT Population 
4. Table 14.1.3.1 Reasons for Exclusion from Per Protocol Population, ITT Population 
5. Table 14.1.4 Demographics, ITT Population 
6. Table 14.1.5 Baseline Characteristics, ITT Population 
7. Table 14.1.6 Previous Therapies for Patchy Alopecia, ITT Population 
8. Table 14.1.6 Medical History, ITT Population 
9. Table 14.1.7 Physical Examination at Screening, ITT Population 
10. Table 14.1.8.1 Prior Medications, Safety Population 
11. Table 14.1.8.2 Concomitant Medications, Safety Population 
12. Table 14.1.9 Study Medication Exposure and Compliance, Safety Population 
Section 14.2 Efficacy 
SALT 
13. Table 14.2.1.1 Summary of SALT Score, Change from Baseline, and Percent Change from 
Baseline by Visit (LOCF), ITT Population 
14.  Table 14.2.1.1a Summary of SALT Score, Change from Baseline, and Percent Change 
from Baseline by Visit (Observed), ITT Population 
15. Table 14.2.1.2 Analysis of Percent Change from Baseline in SALT Score (LOCF), ITT 
Population 
16. Table 14.2.1.3 Analysis of Percent Change from Baseline in SALT Score (LOCF), PP 
Population 
17. Table 14.2.1.4 Analysis of Percent Change from Baseline in SALT Score (Observed), ITT 
Population 
 
18. Table 14.2.1.5 Analysis of Percent Change from Baseline in SALT Score (Observed), PP 
Population 
19. Table 14.2.1.6 Analysis of Percent Change from Baseline in SALT Score (LOCF), 
Exploratory MMRM, ITT Population 
20. Table 14.2.1.7 Analysis of Percent Change from Baseline in SALT Score (LOCF), 
Exploratory MMRM, PP Population 
21. Table 14.2.1.8 Analysis of Change from Baseline in SALT Score (LOCF), ITT Population 
ALODEX 
22. Table 14.2.2.1 Summary of ALODEX Score, Change from Baseline, and Percent Change 
from Baseline by Visit, ITT Population 


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23. Table 14.2.2.2 Analysis of Percent Change from Baseline in ALODEX (LOCF), ITT 
Population 
24. Table 14.2.2.3 Analysis of Change from Baseline in ALODEX Score (LOCF), ITT 
Population 
Responder Endpoints 
25. Table 14.2.3.1 Proportion of Subjects Achieving >=50% Hair Regrowth Based on SALT 
Score, ITT Population 
26. Table 14.2.3.2 Proportion of Subjects Achieving >=50% Hair Regrowth Based on 
ALODEX Score, ITT Population 
27. Table 14.2.3.3 Proportion of Subjects Achieving an Absolute SALT Score <= 10, ITT 
Population 
28. Table 14.2.3.4 Proportion of Subjects with >= 2 Point Improvement in Scalp-ClinRO for 
Target Patch, ITT Population 
29. Table 14.2.3.5 Proportion of Subjects with >= 2 Point Improvement in Scalp-PRO for 
Target Patch, ITT Population 
30. Table 14.2.3.6 Proportion of Subjects with >= 1 Point Improvement in Scalp-ClinRO for 
Entire Scalp, ITT Population 
31. Table 14.2.3.7 Proportion of Subjects with >= 1 Point Improvement in Scalp-PRO for 
Entire Scalp, ITT Population 
Scalp-ClinRO and Scalp-PRO 
32. Table 14.2.4.1 Analysis of Change from Baseline in Scalp-ClinRO for Target Patch, ITT 
Population 
33. Table 14.2.4.2 Analysis of Change from Baseline in Scalp-PRO for Target Patch, ITT 
Population 
34. Table 14.2.4.3 Analysis of Change from Baseline in Scalp-ClinRO for Entire Scalp, ITT 
Population 
35. Table 14.2.4.4 Analysis of Change from Baseline in Scalp-PRO for Entire Scalp, ITT 
Population 
PhGIS and SGIS 
36. Table 14.2.5.1 Analysis of Change from Baseline in Physician Global Impression of 
Severity (PhGIS), ITT Population 
37. Table 14.2.5.2 Analysis of Change from Baseline in Subject Global Impression of Severity 
(SGIS), ITT Population 
PhGIC and SGIC 
38. Table 14.2.6.1   Physician Global Impression of Change (PhGIC) at Week 24, ITT 
Population 
39. Table 14.2.6.2 Subject Global Impression of Change (SGIC) at Week 24, ITT Population 


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Other Efficacy 
40. Table 14.2.7.1   Subject Global Impression of Treatment Satisfaction (SGITS) over Time, 
ITT Population 
41. Table 14.2.8.1   Shift from Baseline to Week 24 in Hair Pull Test Results - Dislodged 
Hairs and Broken Hairs, ITT Population 
42. Table 14.2.9.1 Summary of DLQI Score and Change from Baseline by Visit, ITT 
Population 
43. Table 14.2.9.2 Analysis of Change from Baseline in DLQI Total Score over Time, ITT 
Population 
44. Table 14.2.10.1 AIA–PRO, Total Score, ITT Population  
45. Table 14.2.10.2 AIA–PRO, Cover Hair Loss, ITT Population 
 
46. Table 14.2.10.3 AIA–PRO, Worried about Appearance, ITT Population 
47. Table 14.2.10.4 AIA–PRO, Sad Due to Hair Loss, ITT Population 
48. Table 14.2.10.5 AIA–PRO, Confidence, ITT Population 
49. Table 14.2.10.6 AIA–PRO, Self-Conscious, ITT Population 
50. Table 14.2.10.7 AIA–PRO, Embarrassed, ITT Population 
51. Table 14.2.10.8 AIA–PRO, Unattractive, ITT Population 
52. Table 14.2.10.9 AIA–PRO, Limit Social Activity, ITT Population 
53. Table 14.2.10.10 AIA–PRO, Unwanted Attention, ITT Population 
54. Table 14.2.10.11 AIA–PRO, Sweat in Eyes, ITT Population 
 
55. Table 14.2.10.12 AIA–PRO, Debris in Eyes, ITT Population 
 
56. Table 14.2.10.13 AIA–PRO, Debris in Nose, ITT Population 
Subgroup Analyses 
57. Table 14.2.11.1 Analysis of Percent Change from Baseline in SALT Score (LOCF), ITT 
Population, Baseline SALT < 50 
58. Table 14.2.11.2 Analysis of Percent Change from Baseline in SALT Score (LOCF), ITT 
Population, Baseline SALT ≥ 50 
59. Table 14.2.11.3 Analysis of Percent Change from Baseline in SALT Score (LOCF), ITT 
Population, Whole Scalp Treatment Subgroup 
60. Table 14.2.12.1 Analysis of Percent Change from Baseline in ALODEX Score (LOCF), 
ITT Population, Baseline SALT < 50 
61. Table 14.2.12.2 Analysis of Percent Change from Baseline in ALODEX Score (LOCF), 
ITT Population, Baseline SALT ≥ 50 
62. Table 14.2.13.1 Proportion of Subjects Achieving >=50% Hair Regrowth Based on SALT 
Score, ITT Population, Baseline SALT < 50 
63. Table 14.2.13.2 Proportion of Subjects Achieving >=50% Hair Regrowth Based on 
ALODEX Score, ITT Population, Baseline SALT ≥ 50 


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64. Table 14.2.14.1 Proportion of Subjects Achieving an Absolute SALT Score <= 10, ITT 
Population, Baseline SALT < 50 
65. Table 14.2.14.2 Proportion of Subjects Achieving an Absolute SALT Score <= 10, ITT 
Population, Baseline SALT ≥ 50 
66. Table 14.2.15.1 Proportion of Subjects with >= 2 Point Improvement in Scalp-ClinRO for 
Target Patch, ITT Population, Baseline SALT < 50 
67. Table 14.2.15.2 Proportion of Subjects with >= 2 Point Improvement in Scalp-ClinRO for 
Target Patch, ITT Population, Baseline SALT ≥ 50 
68. Table 14.2.16.1 Proportion of Subjects with >= 2 Point Improvement in Scalp-PRO for 
Target Patch, ITT Population, Baseline SALT < 50 
69. Table 14.2.16.2 Proportion of Subjects with >= 2 Point Improvement in Scalp-PRO for 
Target Patch, ITT Population, Baseline SALT ≥ 50 
70. Table 14.2.17.1 Proportion of Subjects with >= 1 Point Improvement in Scalp-ClinRO for 
Entire Scalp, ITT Population, Baseline SALT < 50 
71. Table 14.2.17.2 Proportion of Subjects with >= 1 Point Improvement in Scalp-ClinRO for 
Entire Scalp, ITT Population, Baseline SALT ≥ 50 
72. Table 14.2.18.1 Proportion of Subjects with >= 1 Point Improvement in Scalp-PRO for 
Entire Scalp, ITT Population, Baseline SALT < 50 
73. Table 14.2.18.2 Proportion of Subjects with >= 1 Point Improvement in Scalp-PRO for 
Entire Scalp, ITT Population, Baseline SALT ≥ 50 
Figures 
74. Figure 14.2.1 LS Mean Percent Change from Baseline (95% CI) in SALT Score Over 
Time by Treatment Group, ITT Population 
75. Figure 14.2.2 LS Mean Percent Change from Baseline (95% CI) in ALODEX Score Over 
Time by Treatment Group, ITT Population 
76. Figure 14.2.3 Proportion of Subjects Achieving a ≥ 50% Hair Regrowth Compared with 
Baseline using SALT Score by Treatment Group, ITT Population 
77. Figure 14.2.4 Proportion of Subjects Achieving a ≥ 50% Hair Regrowth Compared with 
Baseline using ALODEX Score by Treatment Group, ITT Population 
Section 14.3 Safety 
78. Table 14.3.1.1 Overall Summary of Adverse Events, Safety Population 
79. Table 14.3.1.2 Treatment-Emergent Adverse Events by System Organ Classification, 
Preferred Term, and Greatest Severity, Safety Population 
80. Table 14.3.1.3 Treatment-Emergent Adverse Events by System Organ Classification and 
Preferred Term, Safety Population 
81. Table 14.3.1.4 Treatment-Emergent Serious Adverse Events by SOC and PT, Safety 
Population 
82. Table 14.3.1.5 Treatment-Emergent Adverse Events Related to Study Drug by SOC and 
PT, Safety Population 


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83. Table 14.3.1.6 Treatment-Emergent Adverse Events Leading to Discontinuation of Study 
Drug by SOC and PT, Safety Population 
84. Table 14.3.1.7 Study Drug Related Treatment-Emergent Adverse Events Leading to 
Discontinuation of Study Drug by SOC and PT, Safety Population 
85. Table 14.3.4.1.1 Summary of Hematology Results and Change from Baseline by Visit, 
Safety Population 
86. Table 14.3.4.1.2 Summary of Treatment-Emergent Abnormal Hematology by Visit Safety 
Population 
87. Table 14.3.4.2.1 Summary of Serum Chemistry Results and Change from Baseline by 
Visit, Safety Population 
88. Table 14.3.4.2.2 Summary of Treatment-Emergent Abnormal Serum Chemistry by Visit, 
Safety Population 
89. Table 14.3.4.3.1 Summary of Urinalysis Results and Change from Baseline by Visit, 
Safety Population 
90. Table 14.3.4.3.2 Summary of Treatment-Emergent Abnormal Urinalysis by Visit, Safety 
Population 
91. Table 14.3.5.1.1 Summary of ECG Results and Change from Baseline by Visit, Safety 
Population 
92. Table 14.3.5.1.2 Proportion of Subjects with Abnormal ECG Interpretations by Visit, 
Safety Population 
93. Table 14.3.5.2.1 Summary of Vital Signs and Change from Baseline, Safety Population 
 
 


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Section 16.2 Data Listings 
1. Disposition - Early Termination/Study Completion 
2. Protocol Violations 
3. Study Populations 
4. Inclusion/Exclusion Criteria 
5. Demographics 
6. Medical History 
7. History of Alopecia and Previous Therapies for Alopecia 
8. Prior and Concomitant Medications 
9. Study Drug Administration 
10. Study Drug Accountability 
11. SALT Score, ALODEX Score, Scalp-ClinRO, Scalp-PRO 
12. PhGIS and SGIS 
13. PhGIC and SGIC 
14. SGITS 
15. DQLI Questions and Total Score 
16. AIA-PRO Scale Items and Total Score 
17. Hair Quality Assessments – Hair Pull Test 
18. Adverse Events 
19. Serious Adverse Events 
20. Adverse Events Leading to Discontinuation 
21. Laboratory Tests – Panel 
22. Lab Abnormalities 
23. Vital Signs 
24. Physical Examination 
25. ECG 
 
 


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8.2. 
END OF OPEN LABEL EXTENSION PERIOD ANALYSIS 
Section 14.1 Accountability and Baseline Characteristics 
1. Subject Disposition, All Subjects 
2. Demographics, ITT Population 
3. Demographics, PP Population 
4. Updated Medical History, ITT Population  
5. Physical Examination, ITT Population 
6. Concomitant Medications, Safety Population 
7. Study Drug Exposure and Compliance, Safety Population 
Section 14.2 Efficacy  
Tables 
8. Summary of SALT Score, Change, and Percent Change, ITT Population 
9. Summary of ALODEX Score, Change, and Percent Change, ITT Population 
10. Summary of Scalp-ClinRO for Target Patch, ITT Population 
11. Summary of Scalp-ClinRO for Entire Scalp, ITT Population 
12. Summary of Scalp-PRO for Target Patch, ITT Population 
13. Summary of Scalp-PRO for Entire Patch, ITT Population 
14. Summary of Subject Global Impression of Treatment Satisfaction (SGITS), ITT Population 
Figures 
15. Percent Change from Baseline (95% CI) in SALT Score Over Time by Treatment Group, 
ITT Population 
16. Percent Change from Baseline (95% CI) in ALODEX Score Over Time by Treatment 
Group, ITT Population 
Section 14.3 Safety 
17. Overall Summary of Adverse Events, Safety Population 
18. Treatment-Emergent Adverse Events by System Organ Classification, Preferred Term, and 
Greatest Severity, Safety Population 
19. Treatment-Emergent Adverse Events by System Organ Classification and Preferred Term, 
Safety Population 
20. Treatment-Emergent Serious Adverse Events by System Organ Classification and 
Preferred Term, Safety Population 
21. Treatment-Emergent Adverse Events Related to Study Medication by System Organ 
Classification and Preferred Term, Safety Population 
22. Treatment-Emergent Adverse Events Leading to Discontinuation of Study Medication by 
System Organ Classification and Preferred Term, Safety Population 


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23. Overall Summary of Adverse Events, Safety Population (Pooled DB and OLE) 
24. Treatment-Emergent Adverse Events by System Organ Classification, Preferred Term, and 
Greatest Severity, Safety Population (Pooled DB and OLE) 
25. Treatment-Emergent Adverse Events by System Organ Classification and Preferred Term, 
Safety Population Safety Population (Pooled DB and OLE) 
26. Treatment-Emergent Serious Adverse Events by System Organ Classification and 
Preferred Term, Safety Population (Pooled DB and OLE) 
27. Treatment-Emergent Adverse Events Related to Study Medication by System Organ 
Classification and Preferred Term, Safety Population (Pooled DB and OLE) 
28. Treatment-Emergent Adverse Events Leading to Discontinuation of Study Medication by 
System Organ Classification and Preferred Term, Safety Population (Pooled DB and OLE) 
29. Summary of Hematology Results and Change from Baseline by Visit, Safety Population 
30. Summary of Treatment-Emergent Abnormal Hematology by Visit, Safety Population 
31. Summary of Serum Chemistry Results and Change from Baseline by Visit, Safety 
Population 
32. Summary of Treatment-Emergent Abnormal Serum Chemistry by Visit, Safety Population 
33. Summary of Urinalysis by Visit, Safety Population 
34. Summary of Treatment-Emergent Abnormal Urinalysis by Visit, Safety Population 
35. Summary of Vital Signs and Change from Baseline, Safety Population 
 
Section 16.2 Data Listings 
1. Disposition - Early Termination/Study Completion 
2. Protocol Violations 
3. Study Populations 
4. Inclusion/Exclusion Criteria 
5. Demographics 
6. Medical History 
7. Concomitant Medications 
8. Study Drug Administration 
9. Study Drug Accountability 
10. SALT Score, ALODEX Score, Scalp-ClinRO, Scalp-PRO 
11. SGITS 
12. Adverse Events 
13. Serious Adverse Events 
14. Adverse Events Leading to Discontinuation 
15. Laboratory Tests – Panel 
16. Lab Abnormalities 
17. Vital Signs 
18. Physical Examination 
19. ECG