Clinical trial NCT03594227
Conditions: Alopecia
Sponsor: Aclaris Therapeutics, Inc.
Start date: 2018-06-11; Completion date: 2019-06-18
Enrollment: 87 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This Phase 2, multicenter, randomized study will evaluate the safety, tolerability and efficacy of ATI-501 for the treatment of Alopecia Areata (AA), Alopecia Universalis (AU) or Alopecia Totalis (AT) in adult subjects.

Detailed description:
This Phase 2, multicenter, randomized study will evaluate the safety, tolerability and efficacy of ATI-501 for the treatment of Alopecia Areata (AA), Alopecia Universalis (AU) or Alopecia Totalis (AT) in adult subjects. Subjects will be required to have a clinical diagnosis of stable AA, AU, or AT. A total of approximately 80 subjects will be randomized.

Arms: arm 1: ATI-501 low dose - oral administration arm 2: ATI-501 mid dose - oral administration arm 3: ATI-501 high dose - oral administration arm 4: Placebo - oral administration
Interventions: intervention 1: ATI-501 400mg BID (Low dose) intervention 2: ATI-501 600mg BID (Mid dose) intervention 3: ATI-501 800mg BID (High dose) intervention 4: Placebo
Intervention descriptions: intervention 1: ATI-501 400mg BID oral low dose for oral administration intervention 2: ATI-501 600mg BID oral mid dose for oral administration intervention 3: ATI-501 800mg BID high dose for oral administration intervention 4: Placebo - oral administration

Protocol documents:
ICF_002.pdf: 
Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 1 of 14 
INFORMATION AND CONSENT FORM 
 
Study Title: 
A Randomized, Double-Blind, Placebo-Controlled Multicenter Study to Evaluate 
the Safety, Tolerability and Efficacy of ATI-501 Oral Suspension Compared to 
Placebo in Adult Subjects with Alopecia Areata, Alopecia Universalis or Alopecia 
Totalis 
Study #: 
ATI-501-AUAT-201 
Sponsor: 
Aclaris Therapeutics, Inc. 
Study Doctor: 
<<investigator>> 
<<firm name>> 
<<street address>>, <<city>>, <<state>>  <<zip>> 
Telephone Number: <<000-000-0000>> 
After Office Hours: <<000-000-0000>> 
 
The study doctor wants to know if you would like to be part of a research study. 
If you have any questions about or do not understand something in this form, you should ask 
the study doctor or study staff.  You should also discuss your participation with anyone you 
choose in order to better understand this study and your options. 
Participating in a research study is not the same as getting regular medical care.  The purpose 
of regular medical care is to improve your health.  The purpose of a research study is to gather 
information. 
 
WHAT IS THIS STUDY ABOUT? 
Researchers want to find out more about an investigational drug called ATI-501 Oral 
Suspension.  An “investigational” drug is a drug that is being tested as a potential treatment and 
is not approved for sale in the United States by the U.S. Food and Drug Administration (FDA). 
Alopecia is the general medical term for hair loss.  Alopecia areata (AA) starts as mild patchy 
hair loss but can progress. Severe AA occurs in two forms: alopecia totalis (AT) which is total 
hair loss on the scalp (head), or alopecia universalis (AU) which is hair loss of the scalp and the 
rest of the body including eyebrows and eyelashes. 
Alopecia areata is an autoimmune disease. Your body’s immune system protects you from 
disease and infection, but if you have an autoimmune condition or disease, your immune 
system attacks healthy cells in your body by mistake. In AA, the immune system attacks the 
cells in the hair follicles, which causes the hair to stop growing and fall out. 
Currently, there is no proven treatment for AA.  Increases in the understanding of what causes 
AA has led to the development of the new drug ATI-501, which may help to stop the body from 
attacking cells in the hair follicles.  


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 2 of 14 
The main purpose of this study is to see whether ATI-501 Oral Suspension can help regrow hair 
in people with stable patchy alopecia areata, alopecia universalis, or alopecia totalis. 
Researchers also want to find out if the three strengths of ATI-501 Oral Suspension are safe 
and tolerable. 
This study will compare the three strengths of ATI-501 Oral Suspension (400 mg, 600 mg and 
800 mg) with a placebo to see if using ATI-501 Oral Suspension is better than using a placebo.  
The placebo is a substance that looks and tastes like ATI-501 Oral Suspension but has no drug 
in it. 
It is planned that about 120 people with stable patchy alopecia areata, alopecia universalis, or 
alopecia totalis will be in this study. 
Be aware that this form refers to ATI-501 Oral Suspension and the placebo both as “study 
drug.” 
 
HOW DOES ATI-501 ORAL SUSPENSION WORK? 
ATI-501 Oral Suspension is an investigational drug in an oral suspension that is designed to 
allow hair growth to occur again.  ATI-501 Oral Suspension has not been studied in people with 
alopecia areata, and whether or not ATI-501 will work is unknown.  Early signs of hair regrowth 
(if any occurs) may take up to three months. 
 
IS THERE ANYTHING ELSE I CAN DO FOR MY PATCHY ALOPECIA AREATA? 
You do not have to be in this study to get help for your alopecia areata.  Some other things you 
may be able to do are: 
• 
Systemic corticosteroids (anti-inflammatory medications), either topically applied or 
injected into your scalp 
• 
Immunosuppressive treatments (drugs that suppress your immune system) such as:  
o cyclosporine, methotrexate, or etanercept 
• 
Phototherapy such as: 
o phototherapy with psoralen + UVA (PUVA)  
o narrow-band UVB  
o photodynamic therapy (PDT)  
• 
Laser therapy  
• 
Diphenylcyclopropenone (“DPCP”) or squaric acid dibutyl ester (“SADE”) – medications 
that are applied to your scalp to produce an allergic reaction (an approach known as 
topical immunotherapy) 
• 
Topical anthralin (a tar-like topical medication) 
• 
Topical minoxidil (a topical medication approved for male and female pattern baldness) 
Although many products are used for this condition, their effectiveness is uncertain. 
You should discuss your alternatives to participation in this research with the study doctor or 
study staff.  In addition, you may discuss your options with your regular health care provider. 
 


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 3 of 14 
WHO IS PAYING FOR THIS STUDY? 
A company called Aclaris Therapeutics, Inc., the sponsor of the study, is paying for this study. 
<<Quorum may add site-specific conflict-of-interest language to the form based on information 
the site reports to Quorum.>> 
 
WILL IT COST ANYTHING TO BE IN THIS STUDY? 
It will not cost you anything to participate in this study. 
 
HOW LONG WILL I BE IN THE STUDY? 
If you decide to be in this study and the study doctor says you can be in the study, your 
participation will include 10 visits to the study center and will last about 28 weeks, up to a 
maximum of 200 days, with a possibility of up to an additional 30 days for screening results to 
be received. 
You will visit the study center to have the procedures and tests described in this form.  Ask the 
study doctor or study staff about your study visit schedule. 
 
WHAT WILL HAPPEN DURING THIS STUDY? 
If you decide to be in this study, you might have to stop using your regular medication or therapy 
during the entire study.  The study doctor will discuss this with you in detail. 
Each month, the study doctor or study staff will give you a one-month supply of study drug.  You 
will also be given written instructions on how to take the study drug.  Each day you will take one 
single-dose bottle of study drug followed by a full glass of water about 30 minutes after your 
morning meal.  Then 8 to 12 hours later, you will take the second dose of study drug about 30 
minutes after your evening meal followed by a full glass of water.  You should not take the study 
drug on an empty stomach. 
You will be assigned by chance (like flipping a coin) to 1 of the following study groups: 
• 
Group 1:  ATI-501 Oral Suspension, 400mg 
• 
Group 2:  ATI-501 Oral Suspension, 600mg 
• 
Group 3:  ATI-501 Oral Suspension, 800mg 
• 
Group 4:  Placebo Solution (a substance that looks and tastes like a drug, but has no 
drug in it) 
You have an equal chance of being in any of the study groups. 
Neither you nor the study doctor or study staff will be able to pick which study group you are in.  
You will not know, and the study doctor or study staff will not know which study group you are 
in.  The study doctor or study staff can find out if it is necessary to know for your health.  If this 
happens, the study doctor or study staff may not be able to tell you which study group you were 
in until everyone finishes the study. 


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 4 of 14 
While you are in the study, you must: 
• 
Follow the instructions you are given. 
• 
Come to the study center for all visits with the study doctor or study staff. 
• 
Tell the study doctor or study staff about any changes in your health or the way you feel. 
• 
Tell the study doctor or study staff if you want to stop being in the study at any time. 
• 
Use birth control during the study and up to 30 days after the last dose of study drug. 
 
What happens when I come for study visits? 
After you sign this form, the study doctor or study staff will perform the tests and procedures 
listed below when you come in for the study visits.  If you would like more information about 
which tests and procedures will be done at each study visit, ask the study doctor or study staff. 
• 
Demographic Questions:  Ask you to give personal information, such as your name, 
date of birth, sex at birth, and race/ethnicity. 
• 
Health and Medication Questions:  Ask you to answer questions about your health, 
your medical history, your alopecia areata history, and the medications you take. 
• 
Physical Exam:  The study doctor or a member of the study staff will examine your 
overall general appearance, head, eyes, ears, nose, throat, stomach, nervous system, 
muscles and bones, lymphatics, and skin, and will listen to your heart and lungs. 
• 
Vital Signs:  Check your blood pressure by putting a band around your arm (this will 
squeeze your arm for about a minute), check your pulse, listen to you breathe in and out, 
and take your temperature. 
• 
Height, Weight:  See how tall you are, and see how much you weigh.  This will only be 
done at your first visit. 
• 
Blood Testing:  Take some blood through a needle in your arm to do safety and 
laboratory tests.  During the first visit, you will have 6 tubes of blood taken and at other 
visits, you will have 2 tubes of blood drawn. The maximum amount of blood you will have 
taken over 8 months is slightly less than ½ cup for the safety testing.   
o Some of your blood will be used to test for HIV, hepatitis, and tuberculosis. 
 
The study doctor or study staff will tell you if these test results are 
positive. 
 
If required by state law, the study doctor or study staff may report a 
positive test result to the local health department. 
 
The results of these tests must be negative in order for you to be in the 
study. 
• 
Urine Testing:  You will have your urine tested. 
• 
Pregnancy Testing:  Test your blood and/or urine to see if you are pregnant.  You will 
only have pregnancy testing if you are a woman and can have children. 
o The study doctor or study staff will tell you if the pregnancy test results are 
positive. 
o The results of the pregnancy testing must be negative in order for you to be 
enrolled in and continue in the study. 
• 
Electrocardiogram:  An electrocardiogram (ECG) measures the electrical activity of 
your heart. 


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 5 of 14 
• 
Other Questions:  You will be asked about any changes in your health and the 
medications you are taking since the previous study visit. 
• 
Hair Loss Examinations:  The study doctor or study staff will examine your scalp to 
determine the amount of hair loss, the quality of your hair (by gently pulling at hairs at 
the border of areas of hair loss), and the appearance and severity of your hair loss.  The 
study doctor will also assess the amount of hair loss you are experiencing on your face 
[eyebrows, eyelashes, nostrils, and beard (if you are male)] and the rest of your body. 
• 
Questionnaires:  You will be asked to complete a series of questionnaires at different 
visits to describe the appearance & severity of your hair loss and assess the impact of 
hair loss on your life.  You will also be asked at certain visits to rate your satisfaction with 
the study drug results and any changes you may have observed in your hair growth and 
quality. 
• 
Target Patch Identification:  If you have patchy alopecia areata, you will determine 
your most bothersome patchy area on your scalp. 
• 
Photography:  The study doctor or study staff will take pictures of your head and scalp 
(your face will be included in these photographs) to document the hair loss. These 
photographs may be used for research purposes related to the study and for 
presentation to government health authorities, such as the U.S. Food and Drug 
Administration (FDA), at scientific meetings, for scientific publications, for general 
corporate purposes, and may be used for marketing purposes. Your identity will not be 
revealed in these photographs.  Your identifying features, (eyes, mouth, tattoos) will be 
hidden in the photographs.  You do not have to let the study doctor or study staff 
take photographs if you don’t want to; however, if you decline to have these 
pictures taken, you will not be allowed to participate in this study. 
• 
Study Drug:  You will be given a supply of study drug and instructions for how to take 
the study drug. 
• 
Subject Dosing Calendar:  Each month, you will be given a written calendar worksheet 
to document that you have taken your morning and evening doses of study drug. 
 


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 6 of 14 
The following is a schedule of events and tests you will have at each visit: 
 
Events and tests 
Visit 
1 
Visit 
2 
 
Visit 
3 
Visit 
4 
 
Visit 
5 
 
Visit 
6 
 
Visit 
7 
 
Visit 
8 
 
Visit 
9 
Visit 
10 
Informed consent 
 
 
 
 
 
 
 
 
 
 
Physical examination 
 
 
 
 
 
 
 
 
 
 
A discussion about your age, 
birth date, medical, surgical, 
and history of hair loss 
 
 
 
 
 
 
 
 
 
 
Vital Signs 
 
 
 
 
 
 
 
 
 
 
Height and Weight 
 
 
 
 
 
 
 
 
 
 
Blood for safety and urine test 
 
 
 
 
 
 
 
 
 
 
Blood test for pregnancy, if 
you are a woman and can 
have a baby 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test, if you 
are a woman who can have a 
baby 
 
 
 
 
 
 
 
 
 
 
ECG 
 
 
 
 
 
 
 
 
 
 
Scalp examination and 
measurement of hair loss 
 
 
 
 
 
 
 
 
 
 
Identify your most 
bothersome patchy area, if 
applicable 
 
 
 
 
 
 
 
 
 
 
Questionnaire completion 
 
 
 
 
 
 
 
 
 
 
Photographs of your head 
and scalp 
 
 
 
 
 
 
 
 
 
 
Study drug and instructions 
 
 
 
 
 
 
 
 
 
 
Other Questions 
 
 
 
 
 
 
 
 
 
 
 
The results from the tests at Visit 1 will determine whether you are eligible to participate in the 
study.  If you discontinue the study early for any reason, the tests for Visit 9 will be performed. 
 
WILL BEING IN THIS STUDY HELP ME? 
The study drug may help your alopecia areata, but there is no guarantee that being in this study 
will help you.  Your alopecia areata might not get better or may even get worse while you are in 
this study.  You may get placebo, which is a substance that looks and tastes like a drug but has 
no drug in it.  Information from this study might help researchers to better understand alopecia 
areata or come up with new tests or medications to help others in the future. 
 
WHAT ARE THE RISKS TO ME IF I AM IN THIS STUDY? 
This is the first time that ATI-501 has been used on people with alopecia areata.   


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 7 of 14 
In animal testing, the following temporary side effects occurred on the skin where ATI-501 was 
applied: 
• 
Redness 
• 
Swelling 
• 
Skin peeling 
Healthy volunteers took an oral form of ATI-501, and the most frequently reported drug-related 
side effects include: 
• 
Abdominal pain 
• 
Flatulence 
• 
Diarrhea 
• 
Headache 
People who took FDA-approved oral medications similar to ATI-501 experienced: 
• 
Infections (bacterial, viral, fungal, or other infections) 
• 
Abnormal blood tests (decreases in white blood cells and platelets, and increases in liver 
function tests) 
• 
Cancers 
• 
Increased lipids (total cholesterol, high-density lipoprotein cholesterol [also known as 
HDL, the good cholesterol], and low-density lipoprotein cholesterol [also known as LDL, 
the bad cholesterol]) 
Since ATI-501 Oral Suspension is an investigational drug, there may be other risks that are 
unknown.  Please tell the study doctor or study staff right away if you have any side effects.  
Please tell them if you have any other problems with your health or the way you feel during the 
study, whether or not you think these problems are related to the study drug. 
It is possible that using ATI-501 Oral Suspension may change how your regular medications or 
supplements work.  It is very important that you tell the study doctor about any medications or 
supplements before you take them during the study.  You must also avoid receiving any 
vaccinations during the study and for 6 weeks after you take the last dose of study drug.  
Additionally, you should avoid routine contact with children and others who have received recent 
vaccinations during the time you are taking study drug and for 6 weeks following completion of 
the study.   
 
Could I have an allergic reaction? 
Sometimes people have allergic reactions to drugs.  All drugs have a potential risk of an allergic 
reaction, which if not treated promptly, could become life-threatening.  Some things that happen 
during an allergic reaction that could be a sign or symptom of a life-threatening allergic reaction 
(anaphylaxis) are: 
• 
A rash 
• 
A fast pulse 
• 
Sweating 
• 
A feeling of dread 
• 
Swelling around the eyes and mouth 


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 8 of 14 
• 
Swelling of the throat 
• 
Wheezing 
• 
Having a hard time breathing 
• 
A sudden drop in blood pressure (making you feel dizzy or lightheaded) 
• 
Inability to breathe without assistance 
You should get medical help and contact the study doctor or study staff, if you have any of these 
or any other side effects during the study. 
 
What if I am using placebo instead of active drug during the study? 
Some people in the study will get placebo instead of ATI-501 Oral Suspension.  Placebo 
solution is a substance that looks and tastes like a drug but has no drug in it.  If you use placebo 
during the study, it is possible that your alopecia areata may get worse.  Please ask the study 
doctor or study staff if you have any questions about placebo. 
 
If I stop using my regular medication or therapy, what are the risks? 
If you stop your regular medication or therapy to be in the study, your alopecia areata symptoms 
might come back or get worse or your health might get worse. Please tell the study doctor or 
study staff right away if you have any problems when you stop or change your regular 
medication or therapy. 
 
What are the risks of giving blood for this study? 
The study doctor or study staff will take your blood by sticking a needle in your arm.  Some 
problems you might have from this are: 
• 
Pain 
• 
Bruising 
• 
Bleeding or oozing 
• 
Dizziness 
• 
Infection 
 
Risks of study photography 
There are no expected physical risks if the study doctor or study staff takes photos of your head 
and scalp during the study.  It is possible that people who see the study photos will recognize 
you.  
 
Loss of confidentiality 
There is a risk of loss of confidentiality of your information.  You will read more about the 
protection of your information later in this form.  Please ask the study doctor or study staff if you 
would like to know more about how your information will be protected while you are in this study. 


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 9 of 14 
 
What are the risks if I am pregnant or nursing a child during the study? 
If you are a woman who can have a baby, you must not get pregnant during the study or for 
30 days after the last study drug dose.  In animal testing, there were potential toxic effects to 
both the embryo and fetus, indicating a risk to pregnancies.  If you are pregnant or nursing a 
child while using ATI-501 Oral Suspension, there may be risks to you, the embryo, fetus, or 
nursing child.  Nobody knows what all the risks are right now. 
If you are a woman who can have children, the study doctor or study staff will talk to you about 
birth control, which you must use during the study and up to 30 days after the last dose of study 
drug.  
If you think you are pregnant during the study, you must tell the study doctor or study staff 
immediately. 
Women who become pregnant during the study will have to leave the study. The study doctor or 
study staff may ask for information about the pregnancy and the child’s health at birth, and for 
up to 6 weeks after the birth, and may share this information with the sponsor. 
 
What are the risks of fathering a child during the study? 
If you are a sexually active male, you must not father a child during the study or for 30 days 
after the last dose of study drug.  In animal testing, there were potential toxic effects to both the 
embryo and fetus, indicating a risk to pregnancies.  There may be risks to an unborn embryo or 
fetus that you father during or after the study.  Nobody knows what all the risks are right now. 
You must agree to use a barrier method of contraception from the first dose of study drug to at 
least 30 days after the last dose of study drug.   
If you think your partner is pregnant during the study, you must tell the study doctor or study 
staff immediately.  The study doctor or study staff may ask for information about the pregnancy 
and the child’s health at birth, and for up to 6 weeks after the birth, and may share this 
information with the Sponsor. 
 
COULD I HAVE ANY OTHER PROBLEMS WITH MY HEALTH IF I AM IN THIS STUDY? 
It is possible that you could have problems and side effects of ATI-501 Oral Suspension that 
nobody knows about yet, which include your alopecia areata getting worse. 
Ask the study doctor if you have questions about the signs or symptoms of any side effects that 
you read about in this consent form. 
 
WILL I RECEIVE ANY NEW INFORMATION DURING THE STUDY? 
If the study doctor or study staff learns any new information that might change your mind about 
continuing in the study, the study doctor or study staff will tell you about it. 
 


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 10 of 14 
WHAT IF I GET HURT OR SICK WHILE I AM IN THIS STUDY? 
If, during the course of this study, any injury occurs to you as a direct result of the administration 
of the study drug or properly performed procedures, the Sponsor agrees to pay all medical 
expenses necessary to treat such injury: 1) to the extent you are not otherwise reimbursed by 
medical insurance; and 2) provided you have followed the directions of the study doctor. 
The compensation offered by the Sponsor for any injury which occurs to you as a direct result of 
the administration of the study drug or poorly performed procedures by the study doctor or study 
staff, will be paid after the Sponsor receives all appropriate documentation and completes its 
review, to its satisfaction, of all documentation regarding your claim for injury. 
You will not lose or give up any of your legal rights or release the Sponsor, the study doctor, the 
study staff, or study site from liability for negligence or intentional misconduct by signing this 
consent document. 
There are no plans to provide financial compensation for such things as lost wages, disability, or 
discomfort due to injury. 
 
WILL I RECEIVE PAYMENT? 
<<Quorum will add site-specific compensation language to the form based on information the 
site reports to Quorum.>> 
 
DO I HAVE TO BE IN THIS STUDY? 
Your participation in this study is voluntary.  You can decide not to be in the study and you can 
change your mind about being in the study at any time.  There will be no penalty to you, and you 
won’t lose any benefits except for benefits having to do with the study.  If you want to stop being 
in the study, tell the study doctor or study staff. 
The study doctor or study staff or Sponsor can remove you from the study at any time, even if 
you want to stay in the study.  This could happen if, for example: 
• 
The study doctor or study staff believes it is best for you to stop being in the study. 
• 
You do not follow directions about the study. 
• 
The Sponsor stops the study for any reason. 
If you stop being in the study early, the study doctor or study staff may ask you some questions 
about being in the study.  The study doctor or study staff may ask you to participate in some 
procedures or tests to help you leave the study safely and/or to collect more information for the 
study. 
If you leave the study, the study doctor and study staff will still be able to use your information 
that they have already collected. 
If you change your mind later, be aware that your samples may or may not be withdrawn from 
the research, depending on the sponsor’s policies. You can ask the study doctor or study staff 
about this. 
 


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 11 of 14 
HOW WILL MY INFORMATION BE KEPT CONFIDENTIAL? 
Your identity will be protected as required by law and according to any policies the study center 
or sponsor may have.  Be aware that your study records (which include your medical records, 
your signed consent form, and other information) will be shared as needed for the study.  For 
example, the U.S. Food and Drug Administration (FDA), the sponsor, and Quorum Review may 
look at your study and medical records. 
Your blood and urine samples will not be labeled with your name or other directly identifying 
information.  Your samples will have a code (a unique subject identifier) instead.  The list that 
matches the code with your name will be stored separately from your samples.  Your samples 
will be kept only until we are able to complete the tests described in this form, and then your 
samples will be destroyed. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law.  This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time. 
 
WHO CAN I TALK TO ABOUT THIS STUDY? 
In the event of an emergency, dial 911 immediately. 
If you require emergency care, be sure to tell the emergency care provider about your 
participation in this study.  Contact the study doctor or study staff as soon as possible. 
You can ask questions about the study at any time.  You can call the study doctor or study staff 
at any time if you have any concerns or complaints.  You should call the study doctor or study 
staff at the phone number listed on page 1 of this form if you have questions about the study 
procedures, study costs (if any), study payment (if any), or if you get hurt or sick during the 
study. 
Quorum Review reviewed this study.  Quorum Review is a group of people who review research 
studies to protect the rights and welfare of research participants.  Review by Quorum Review 
does not mean that the study is without risks.  If you have questions about your rights as a 
research participant, if you are not able to resolve your concerns with the study doctor or study 
staff, if you have a complaint, or if you have general questions about what it means to be in a 
research study, you can call Quorum Review or visit the Quorum Review website at 
www.QuorumReview.com. 
Quorum Review is located in Seattle, Washington. 
Office hours are 8:00 AM to 5:00 PM Pacific Time, Monday through Friday. 
Ask to speak with a Research Participant Liaison at 888-776-9115 (toll free). 
 
HOW WILL MY INFORMATION BE USED AND SHARED FOR THIS STUDY? 
This section explains who will use and share your health information if you agree to be in this 
study.  You must authorize this use and sharing of your information by signing this form or you 
cannot be in the study.  


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 12 of 14 
The study doctor and study staff will collect, use, and share health information about you, 
including any information needed to do the study and other identifying information about you, 
such as your name, address, phone number, or social security number.  The information used 
and shared will include: 
• 
information from your medical records 
• 
information collected about you during the research, including study visits, notes, tests, 
procedures, photographs, etc. 
Your information may be used and shared with these people for the following purposes: 
• 
The study doctor and study staff to conduct this research. 
• 
The sponsor, Aclaris Therapeutics, Inc.; people who work with or for the sponsor; and 
other researchers involved in this study.  These people will use your information to 
review the study, to check the safety and results of the study drug, and to seek 
government approval of ATI-501 Oral Suspension. 
• 
Others required by law to review the quality and safety of research, including the U.S. 
Food and Drug Administration (FDA), Department of Health and Human Services, Office 
for Human Research Protections, other government agencies in the United States and 
other countries, and Quorum Review. 
• 
A public health authority that is authorized by law to collect or receive such information 
for the purpose of preventing or controlling disease, injury, or disability, and conducting 
public health surveillance, investigations, or interventions. 
After your information is shared with the people and companies listed above, the law may not 
require them to protect the privacy of your information.   
To maintain the integrity of this research, you might not have access to any health information 
developed as part of this study until it is completed.  At that point, you generally would have 
access to your health information. 
You can cancel your authorization to use and share your information at any time by writing a 
letter to the study doctor.  If you cancel your authorization, you will not be able to continue in the 
study.   
If you cancel your authorization, the study doctor and study staff will still be able to use and 
share your information that they have already collected. 
This authorization to use and share your information expires in 50 years. 
 
 
 
 
 
Signature of Participant 
 
 
 
 
 
Date 
 


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 13 of 14 
<<Quorum staff: Include the following for Indiana sites: 
In Indiana, you must complete the following information: 
 
 
 
 
 
 
 
Participant’s Street Address 
 
 
 
 
 
 
 
Participant’s City, State, ZIP>> 
 
REGULAR DOCTOR OR SPECIALIST NOTIFICATION OPTION 
For your safety, you or the study doctor should tell your regular health care provider that you are 
in this study.  This is recommended so that your primary care doctor may contact the study 
doctor if they have any concerns or questions about your care. 
Please indicate below whether you want us to notify your regular doctor or your specialist of 
your participation in this study. 
 
 
Yes, I want the study doctor to inform my regular doctor/specialist of my participation in 
this study: 
 
 
 
 
 
Name of Doctor 
 
 
 
 
 
 
Phone 
 
 
No, I do not want the study doctor to inform my regular doctor/specialist of my 
participation in this study. 
 
I do not have a regular doctor/specialist. 
 
The study doctor is my regular doctor/specialist. 


Information and Consent Form 
Aclaris Therapeutics, Inc. 
ATI-501-AUAT-201 
 
Initials __________    Date __________ 
Version 1, dated 05/01/18 
Page 14 of 14 
CONSENT 
I have read this form, and I have been able to ask questions about this study. The study doctor 
or study staff has talked with me about this study. They have answered all my questions.  
I voluntarily agree to be in this study. 
By signing this form, I do not give up any of my legal rights.  I will get a signed copy of this 
consent form. 
 
 
 
Printed Name of Participant 
 
 
 
 
 
Signature of Participant 
 
 
 
 
 
Date 
 
 
I attest that the individual providing consent had enough time to consider this information, had 
an opportunity to ask questions, and voluntarily agreed to participation in this study. 
 
 
 
Printed Name of Person Explaining Consent 
 
 
 
 
 
Signature of Person Explaining Consent 
 
 
 
Date 
 
 
I attest that I or my representative discussed this study with the individual providing consent. 
 
 
 
Signature of Principal Investigator or Sub-Investigator 

Prot_000.pdf: 
Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 1 of 90 
CONFIDENTAL 
 
  
 
CLINICAL STUDY PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled Multicenter Study to 
Evaluate the Safety, Tolerability and Efficacy of ATI-501 Oral Suspension 
Compared to Placebo in Adult Subjects with Alopecia Areata, Alopecia 
Universalis or Alopecia Totalis 
Amendment 4 
 
Compound: 
 
ATI-501 
US IND Number: 
129, 539 
 
Protocol Number: 
 
 
 
 
 
ATI-501-AUAT-201 
 
Phase: 
 
2 
 
Sponsor 
Aclaris Therapeutics, Inc. 
640 Lee Road 
Suite 200 
Wayne, PA 19087 
Telephone: 484-324-7933 
Facsimile: 484-320-2344 
 
 
Medical Monitor 
Jeffrey Sugarman, MD, PhD 
Telephone: 707-545-4537 
Facsimile: 707-545-6723 
pediderm@yahoo.com  
 
 
Study Contact 
Sue Moran, RN, MSN 
Sr. Director, Clinical Development 
Aclaris Therapeutics, Inc. 
640 Lee Road 
Suite 200 
Wayne, PA 19087 
Telephone: 484-329-2129 
Cell:  484-999-7492 
E-mail:  
smoran@aclaristx.com 
 
 
Safety Contact: 
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-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 3 of 90 
CONFIDENTAL 
 
  
 
INVESTIGATOR’S AGREEMENT 
 
I have received and read the Investigator’s Brochure for ATI-501.  I have read the ATI-501-
AUAT-201 protocol and agree to conduct the study as outlined.  I agree to maintain the 
confidentiality of all information received or developed in connection with this protocol. I will 
conduct the trial in accordance with the principles of ICH Good Clinical Practice and the 
Declaration of Helsinki. 
 
I will maintain as confidential all written and verbal information provided to me by the Sponsor, 
including but not limited to, the protocol, case report forms, investigator’s brochure, material 
supplied at investigator meetings, minutes of teleconferences, etc.  Such materials will only be 
provided as necessary to site personnel involved in the conduct of the trial, involved IRBs or 
local regulatory authorities. 
 
I will obtain written informed consent from each prospective trial subject or each prospective 
trial subject’s legal representative prior to conducting any protocol-specified procedures.  The 
Informed Consent Document used will have the approval of the IRB appropriate for my 
institution. 
 
I will maintain adequate source documents and record all observations, treatments and 
procedures pertinent to trial subjects in their medical records.  I will accurately complete the case 
report forms supplied by the Sponsor in a timely manner.  I will ensure that my facilities and 
records will be available for inspection by representatives of the Sponsor, the IRB, and/or local 
regulatory authorities.  I will ensure that I and my staff are available to meet with Sponsor 
representatives during regularly scheduled monitoring visits. 
 
I will notify the Sponsor within 24 hours of any serious adverse events.  Following this 
notification, an initial written report describing the serious adverse event will be provided to the 
Sponsor within 24 hours of Investigator awareness of the event. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
                    
 
 
 
 
 
 
Signature of Investigator                                                     Date 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 4 of 90 
CONFIDENTAL 
 
  
 
AMENDMENT HISTORY 
Amendment 1.0 (Protocol Version 2.0 dated 20Jul2018): The primary reason for Amendment 1.0, 
Protocol Version 2.0 dated 20Jul2018 was to decrease the number of subjects enrolled in the study which 
are sufficient to explore the efficacy and safety in this initial Phase 2 study.  In addition, a substudy was 
added to determine the trough levels of ATI-502 in the blood and pharmacodynamic effects at trough.  
Amendment 2.0 (Protocol Version 3.0 dated 19Sep2018): The primary reason for Amendment 2.0, 
Protocol Version 3.0, dated 19SEP2018 was to add additional safety assessments, specifically – clinical 
laboratory testing (chemistry and hematology) at Visit 5, Visit 7 and Visit 8 and to remove 
pharmacodynamic testing in a subset of subjects at Visit 2, Visit 4, Visit 6 and Visit 9.   
Amendment 3.0 (Protocol Version 4.0 dated 08Nov2018): The primary reason for Amendment 3.0, 
Protocol Version 4.0, dated 08NOV2018 is to give subjects the option to initiate treatment with ATI-502 
Topical Solution, 0.46% to explore if hair regrowth can be maintained or continued following cessation of 
treatment with ATI-501 Oral Suspension.  Eligible subjects will be given the option at Visit 9 to enter an 
open-label study ATI-502-AA-203.   
AMENDMENT RATIONALE 
The purpose of Protocol Version 5.0 dated 09APR2019 (Protocol Amendment 4.0) is to clarify the 
primary endpoint will be conducted on the ITT population.  In addition, other clarifications were made to 
the statistical methods as detailed in the following table.  All previous amendments have been 
incorporated into the protocol dated 09APR2019. 
 
MAJOR PROTOCOL CHANGES 
Protocol 
Version 
Date 
Section 
Revisions 
Version 
5.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
09APR2019 
Statistical 
Methods 
-Synopsis,  
-Section 9.4.1 
-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). 
-Clarified:  efficacy variable is “percent change from baseline” 
and not “mean percent change from baseline”. 
Secondary 
Efficacy 
Analyses 
-Synopsis 
-Section 9.4.2 
-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 
Deleted:  Dichotomous variables will be analyzed using Chi-
square tests.  Ordinal and continuous variables will be analyzed 
using appropriate Analysis of Variance models. 
Section 9.4 
-Deleted the statement that the PP population would be used for 
all efficacy analyses 
-Clarified that Hair regrowth is determined based on both percent 
change from baseline and absolute change from baseline. 
Synopsis,  
Section 9.5 
Dropped the chi-square test for the overall incidence of AE 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 5 of 90 
CONFIDENTAL 
 
  
 
SYNOPSIS 
Name of Sponsor/Company: Aclaris Therapeutics, Inc. 
 
Name of Investigational Product: ATI-501 Oral Suspension 
 
Name of Active Ingredient: ATI-501 
 
Title of Study: A Randomized, Double-Blind, Placebo-Controlled Multicenter Study to Evaluate the 
Safety, Tolerability and Efficacy of ATI-501 Oral Suspension Compared to Placebo in Adult Subjects 
with Alopecia Areata, Alopecia Universalis or Alopecia Totalis 
Study center(s): Approximately 25 US study centers 
Studied period (years):  
Estimated date first patient enrolled: June 2018 
Estimated date last patient completed: July 2019 
Phase of development: 2 
 
Objectives:  
Primary: 
• 
To evaluate the safety, tolerability and efficacy of ATI-501 Oral Suspension, 400 mg, 600 mg, 
800 mg compared to Placebo Oral Suspension in subjects with alopecia areata (AA), alopecia 
universalis (AU) or alopecia totalis (AT) 
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 
• 
To assess the level of ATI-502 in the blood at trough 
 
Methodology:  
This Phase 2, multicenter, randomized study will evaluate the safety, tolerability and efficacy of ATI-
501 for the treatment of AA, AU, or AT in adult subjects.  Subjects will be required to have a clinical 
diagnosis of stable AA, AU, or AT with 30% to 100% total scalp hair loss for a duration of at least 6 
months up to and including 12 years.  A total of 80 subjects will be randomized with approximately 
40 subjects enrolled with AU or AT.  Subjects will be randomized to a 1:1:1:1 ratio: 
• 
ATI-501 Oral Suspension, 400 mg, BID for 24 weeks (6 months)  
• 
ATI-501 Oral Suspension, 600 mg, BID for 24 weeks (6 months) 
• 
ATI-501 Oral Suspension, 800 mg, BID for 24 weeks (6 months) 
• 
Placebo Oral Suspension, BID for 24 weeks (6 months) 
 
During the screening period, subjects will be assessed for eligibility into the study.  Subjects 
qualifying for protocol treatment based on the outcome of screening procedures will be randomized to 
take 400 mg, 600 mg, 800 mg or placebo suspension twice-daily within approximately 30 minutes 
following morning and evening meals for 24 weeks.   Assessment of response to treatment will be 
performed at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and post-treatment Week 28.  


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 6 of 90 
CONFIDENTAL 
 
  
 
Safety and tolerability will be evaluated at each study visit by assessment of adverse events, clinical 
laboratory tests, and vital signs, and at select visits, ECGs will be completed.  
 
Subjects who complete study visits through Visit 9 will have the option to roll over into an open-label 
study ATI-502-AA-203.  Subjects who withdraw consent or meet study medication discontinuation 
criteria (Section 3.4.1.2) on study ATI-501-AUAT-201 will not be eligible for roll-over to study ATI-
502-AA-203.  Subjects who complete the assessments for Visit 9 and then meet study ATI-502-AA-
203 entry criteria and provide written consent will skip post-treatment Visit 10.   Subjects who are not 
eligible for ATI-502-AA-203 or who decline to participate should return for the final Visit 10 
assessments. 
Select Sites: 
At approximately six sites, 24 subjects will have additional blood samples taken for pharmacokinetic 
analyses.  Blood samples will be taken at predose at Visit 2 and at trough at Visit 4, Visit 6 and Visit 
9 to determine the concentration of ATI-502 in the blood at trough. 
Number of subjects (planned): Approximately 95 with approximately 45 subjects enrolled with AT 
or AU. 
Male and female subjects, 18 years of age or older, with a clinical diagnosis of stable AA, AU or AT 
of the scalp, who meet all the inclusion criteria and none of the exclusion criteria, will be eligible to 
enroll in this study.  
 
Inclusion Criteria: 
Subjects must meet the following criteria to be eligible for participation in the study: 
1. Able to comprehend and willing to sign an Informed Consent Form (ICF). 
2. Male or non-pregnant, non-nursing female ≥ 18 years old at the time of informed consent. 
3. Have a clinical diagnosis of stable AA, AU or AT (Stable is defined as no current areas of 
spontaneous terminal scalp hair regrowth). 
4. Have a Severity of Alopecia Tool (SALT) score of at least 30% to 100% total scalp hair loss 
determined by the study investigator at Screening (Visit 1) and Baseline (Visit 2). 
5. Subjects with 30% to 95% scalp hair loss (based on SALT score) must 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 (ASAA).  The target patch is defined as the most 
bothersome patchy area of hair loss as identified by the subject (Refer to Section 7.1). 
6. Have a duration of the current episode of stable scalp hair loss for a minimum of 6 months 
and a maximum duration of hair loss of 12 years (inclusive). [Current episode is defined as 
the period of the current presentation of hair loss (AA, AU or AT)]. 
7. If the subject is a woman of childbearing potential (WOCBP), she must have: 
• 
Negative serum pregnancy tests at Screening (Visit 1); and 
• 
A negative urine pregnancy test at Baseline (Visit 2); and  
• 
Agree to not be planning a pregnancy during the study duration and use a highly 
effective method of contraception for the duration of the study and 30 days after the 
last dose of study medication. (Refer to Section 8.4.2). 
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 and hair dyeing throughout the study period. 
Subjects who shave their scalp must be willing to refrain from shaving their scalp for at least 
two weeks prior to each study visit, as determined by the investigator based on the ability to 
assess visible scalp hair growth. Hair trimming outside the treatment areas to maintain the 
current hair style is permitted.  


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 7 of 90 
CONFIDENTAL 
 
  
 
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 a 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 a maintenance dose throughout the study.  
13. Sexually active male subjects must agree to use a barrier method of contraception with any 
WOCBP partner(s) from the first dose of study medication to at least 30 days after the last 
dose of study medication. 
 
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 dose of study medication.  
2. Diffuse alopecia areata. [Diffuse alopecia areata is defined as the absence of the typical 
patchy distribution of hair loss (in subjects with <95% total scalp hair loss) with hair thinning 
distributed throughout the scalp.] 
3. Concomitant hair loss disorder (by history or physical exam) such as androgenetic alopecia 
(AGA) or scarring alopecia (e.g., cicatricial alopecia, frontal fibrosing alopecia, etc.). 
Subjects without a prior known history of 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 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, AU or AT 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 autoimmune, metabolic, hepatic, 
endocrine, renal, gastrointestinal, pulmonary, cardiovascular, genitourinary, or hematological 
disease, neurologic or cerebral disorders, 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 (e.g. 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. Refer to Exclusion Criterion 12 for 
herpes zoster, herpes simplex, or cytomegalovirus infections.    
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 (HepB surface Ab without the presence of Hep B surface Ag) will be allowed to 
participate. 
12. History of recurrent herpes zoster (more than one episode) or disseminated herpes zoster (a 
single episode) or disseminated herpes simplex (single episode) or cytomegalovirus (CMV) 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 8 of 90 
CONFIDENTAL 
 
  
 
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. [Subjects with any 
Screening laboratory values meeting the Study Medication Interruption Criteria found in 
Table 2 must have repeat lab testing performed with results meeting the minimum criteria for 
resumption in order to initiate treatment at Baseline (Visit 2)]. 
14. Subjects with absolute neutrophil count <1,800/µL, or platelet count <130,000/µL. 
15. Subjects who have received any of the following treatments for the timeframes specified 
below: 
• 
Disease Modifying Anti-Rheumatic Drugs (DMARDS), Biologics or 
immunosuppressants, including but not limited to: anakinra, adalimumab, azathioprine, 
corticosteroids, cyclosporine, etanercept, infliximab, methotrexate, TNF inhibitors, 
ustekinumab within 1 month or 5 half-lives (whichever is greater) of Baseline (Visit 2). 
• 
Plaquenil within 2 months of Baseline (Visit 2). 
• 
JAK inhibitors (oral or topical) within 6 months of Baseline (Visit 2).   
• 
Intralesional steroids or platelet rich plasma injections in the scalp within 1 month of 
Baseline (Visit 2). 
• 
Topical treatments on the scalp with anthralin, bimatoprost, corticosteroids, 
diphencyprone, diphenylcyclopropenone (DPCP), squaric acid dibutylester (SADBE), 
minoxidil, pimecrolimus, or tacrolimus within 1 month of Baseline (Visit 2). 
• 
Phototherapy (narrow band Ultraviolet B [NB UVB] or broadband therapy) within 4 
weeks of Baseline (Visit 2). 
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 
Baseline (Visit 2).   
17. Any condition possibly affecting oral drug absorption, e.g., gastrectomy, clinically significant 
diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass.  
Procedures such as gastric banding are not exclusionary. 
18. Sensitivity to any of the ingredients in the study medications. 
19. Unwillingness to refrain from weaves, hair extensions, or shaving of the scalp for at least two 
weeks prior to a study visit, at the discretion of the investigator, based on the ability to assess 
hair growth.  
20. Screening ECG findings of: 
• 
QTcF >450msec for males or >470msec for females (use of the ECG algorithm is 
acceptable for this purpose) 
• 
Heart rate ≤45 or ≥ 100 beats/minutes (A subject with a heart rate < 45 beats/min 
may be enrolled if in the opinion of the investigator the heart rate is not 
clinically significant).  
• 
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 
21. Vaccination with a live or attenuated vaccine within 6 weeks prior to Baseline (Visit 2) or 
planned vaccination with these vaccines at any time during treatment or within 6 weeks 
following discontinuation of study medication.  


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 9 of 90 
CONFIDENTAL 
 
  
 
22. Participation in an investigational study with ATI-502 Topical Solution.  
23. Subjects unwilling to have photographs taken for study purposes. 
Investigational product, dosage and mode of administration:  
ATI-501 Oral Suspension, 400 mg, 600 mg, 800 mg or placebo will be taken approximately 30 
minutes after morning and evening meal followed by a large glass of water, twice-daily for 24 weeks.  
Duration of treatment:  
All subjects will take 400 mg, 600 mg, 800 mg or placebo oral suspension twice daily for 24 weeks 
followed by a 4-week post-treatment follow up period.   
Reference therapy, dosage and mode of administration:  
Placebo suspension, twice daily, oral 
Criteria for evaluation: 
Primary Efficacy:   
• 
The primary efficacy endpoint is the mean percent change from Baseline in the Severity of 
Alopecia Tool (SALT) score at Week 24 (Visit 9).   
 
Secondary Efficacy: 
• 
Mean percent change from Baseline in the Alopecia Density and Extent Score (ALODEX) score 
at Week 24. 
• 
Change from Baseline in the SALT score at Week 24 (Visit 9) with additional analyses at each 
applicable post-baseline visit where data are available. 
• 
Change from Baseline in the Alopecia Density and Extent Score (ALODEX) score at Week 24 
(Visit 9) with additional analyses at each applicable post-baseline visit where data are available. 
• 
Proportion of subjects in each treatment arm achieving at least a 50% reduction in ALODEX 
score at Week 24 (Visit 9) with additional analyses at each applicable post-baseline visit where 
data are available compared to Baseline. 
• 
Proportion of subjects in each treatment arm achieving at least a 50% reduction in SALT score at 
Week 24 (Visit 9) with additional analyses at each applicable post-baseline visit where data are 
available compared to Baseline. 
• 
Change from Baseline in the Alopecia Scalp Appearance Assessment (ASAA) (Patient-reported 
outcome [PRO]) at Week 24 (Visit 9) with additional analyses at each applicable post-baseline 
visit where data are available. 
• 
Change from Baseline in the Alopecia Scalp Appearance Assessment (ASAA) (Clinician-
reported outcome [ClinRO]) at Week 24 (Visit 9) with additional analyses at each applicable 
post-baseline visit where data are available. 
• 
Change from Baseline in the Physician Global Impression of Severity (PhGIS) at Week 24 (Visit 
9) with additional analyses at each applicable post-baseline visit where data are available. 
• 
Change from Baseline in Alopecia Facial Hair Appearance Assessment (AFHA) (Clinician and 
Subject) at Week 24 (Visit 9) with additional analyses at each applicable post-baseline visit where 
data are available. 
• 
Change from Baseline in the Subject Global Impression of Severity (SGIS) at Week 24 (Visit 9) 
with additional analyses at each applicable post-baseline visit where data are available. 
• 
Change from Baseline in the subject reported Alopecia Impact Assessment (AIA) at Week 24 
(Visit 9) with additional analyses at each applicable post-baseline visit where data are available. 
• 
Subject Global Impression of Treatment Satisfaction (SGITS) at Week 24 (Visit 9) with 
additional analyses at each applicable post-baseline visit where data are available. 
• 
Change from Baseline in the Subject Global Satisfaction with Hair Quality (SGSHQ) at Week 24 
(Visit 9) with additional analyses at each applicable post-baseline visit where data are available. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 10 of 90 
CONFIDENTAL 
 
  
 
• 
Change in Dermatology Life Quality Index (DLQI) total score between Baseline and Week 24 
(Visit 9) with additional analyses at each applicable post-baseline visit where data are available. 
• 
Global Impression of Change (Clinician and Subject) at Week 24 (Visit 9). 
 
Other Assessments: 
• 
Hair quality assessment including normalization of exclamation point hairs and hair shedding will 
be described. 
• 
Vellus and Indeterminate scalp hair will be described. 
• 
Non-scalp hair assessments (body and nasal hair) will be described. 
 
Pharmacokinetic: 
The concentration of ATI-502 in the blood predose at Visit 2 and at trough at Visit 4, Visit 6 and Visit 
9 will be measured by a bioanalytical lab using fully validated analytical methods.  
 
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. 
Statistical Methods: 
Sample Size/ Power Calculations 
The planned sample size is approximately 95 enrolled subjects with approximately 45 subjects 
enrolled with AT or AU.  The sample size estimate was based on published results from a similar 
study (Crispin et al.  2016) where 32% of subjects receiving active drug achieved at least a 50% 
relative reduction in hair loss (SALT50) under similar conditions.  For the current study, the primary 
efficacy analysis is mean % change in hair loss, evaluated using SALT scores.  That analysis is 
expected to have greater statistical sensitivity than the SALT50 responder analysis, which is also a 
secondary efficacy analysis in the current study.   
 
We assume the pooled results of 600mg and 800mg treatment groups in the current study will achieve 
the same or higher SALT50 response rate (32%) as the published results above, and pooled Vehicle 
plus 400mg treatment groups will not achieve more than a 6% SALT50 response rate.  Based on a 
comparison of those two pooled groups, the current study is anticipated to have no less than 80% 
power with a 10% subject dropout rate for the SALT50 analysis.  Because the primary efficacy 
analysis of mean percent reduction in hair loss using SALT scores is expected to be more sensitive 
than the SALT50 responder analysis, the power for the primary analysis is also expected to be no less 
than 80%. 
 
Statistical Methods 
The primary efficacy variable will be the percent change from Baseline in the SALT score at Week 
24 (Visit 9).  This represents the percentage of hair regrowth.  It will be calculated as the change from 
baseline (Visit 2) to Week 24 (Visit 9), divided by the baseline 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 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 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 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 11 of 90 
CONFIDENTAL 
 
  
 
will include fixed effect terms for treatment, study visit, baseline SALT score group (<50, >=50), and 
treatment by baseline 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 
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 change from Baseline in the ALODEX score, ASAA 
(CR & SR), AFHA (CR & SR), PhGIS, SGIS, AIA, SGSHQ, and DLQI as well as the proportion of 
subjects achieving a ≥ 50% hair growth compared with Baseline based upon the SALT score and 
ALODEX score, separately.  SGITS responses at Week 12, 24, and 28 will be summarized.  Various 
secondary responder efficacy endpoints will be defined based upon the SALT score, the ALODEX 
score 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 9) will be used in the psychometric evaluation of the scores from the 
ASAA (CR and SR), respectively.  Non-Scalp Hair Loss Assessment, Vellus and Indeterminate Hair 
Assessment and Hair Quality Assessment including normalization of exclamation point hairs and hair 
shedding will be described.  The analysis for percent change in ALODEX score will used 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. 
 
Pharmacokinetic Analyses 
The concentration of ATI-502 in the blood will be summarized (mean [SD], minimum, median 
maximum) predose at Visit 2 and at trough at Visit 4, 6, and 9.   
 
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 
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-dose 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.  
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 12 of 90 
CONFIDENTAL 
 
  
 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES  
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
AMENDMENT HISTORY .............................................................................................................4 
AMENDMENT RATIONALE ........................................................................................................4 
SYNOPSIS. ......................................................................................................................................5 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ..................................12 
LIST OF TABLES .........................................................................................................................16 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................17 
1. 
INTRODUCTION ......................................................................................................19 
1.1. 
Overview of Alopecia Areata .....................................................................................19 
1.2. 
Immunopathology & Pathophysiology of AA ............................................................20 
1.3. 
Previous Clinical Study Experience with ATI-501 ....................................................21 
1.4. 
Study Rationale ...........................................................................................................22 
2. 
TRIAL OBJECTIVES AND ENDPOINTS ...............................................................24 
2.1. 
Primary Objective .......................................................................................................24 
2.2. 
Secondary Objectives .................................................................................................24 
2.3. 
Primary Efficacy Endpoint .........................................................................................24 
2.4. 
Secondary Efficacy Endpoints ....................................................................................24 
2.5. 
Other Assessments ......................................................................................................25 
2.6. 
Pharmacokinetic Endpoints ........................................................................................25 
2.7. 
Safety Endpoints .........................................................................................................25 
3. 
INVESTIGATIONAL PLAN .....................................................................................26 
3.1. 
Overall Study Design ..................................................................................................26 
3.2. 
Number of Subjects ....................................................................................................26 
3.3. 
Treatment Assignment ................................................................................................26 
3.4. 
Dose Adjustment Criteria ...........................................................................................26 
3.4.1. 
Safety Criteria for Adjustment or Stopping Doses .....................................................27 
3.4.1.1. 
Study Medication Interruption ....................................................................................27 
3.4.1.2. 
Study Medication Discontinuation .............................................................................27 
3.5. 
Criteria for Study Termination ...................................................................................28 
3.6. 
Study Procedures ........................................................................................................29 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................34 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 13 of 90 
CONFIDENTAL 
 
  
 
4.1. 
Subject Inclusion Criteria ...........................................................................................34 
4.2. 
Subject Exclusion Criteria ..........................................................................................35 
4.3. 
Subject Withdrawal Criteria .......................................................................................37 
5. 
TREATMENT OF SUBJECTS ..................................................................................38 
5.1. 
Study Medication Administration...............................................................................38 
5.2. 
Concomitant Medications ...........................................................................................38 
5.3. 
Grooming ....................................................................................................................39 
5.4. 
Prohibited Medications ...............................................................................................39 
5.5. 
Vaccine Guidelines .....................................................................................................39 
5.6. 
Treatment Compliance ................................................................................................40 
5.7. 
Randomization and Blinding ......................................................................................40 
5.7.1. 
Unblinding the Study Medication ...............................................................................40 
6. 
STUDY MEDICATION MATERIALS AND MANAGEMENT .............................42 
6.1. 
Study Medication ........................................................................................................42 
6.2. 
Packaging and Labeling ..............................................................................................42 
6.3. 
Study Medication Storage ...........................................................................................42 
6.4. 
Study Medication Accountability and Disposal .........................................................42 
7. 
ASSESSMENT OF EFFICACY ................................................................................44 
7.1. 
Alopecia Target Scalp Patch Identification ................................................................44 
7.2. 
Subject Reported Outcome Assessments ....................................................................44 
7.2.1. 
Alopecia Scalp Appearance Assessment (ASAA) .....................................................45 
7.2.2. 
Alopecia Facial Hair Appearance Assessment (AFHA) for AA, AT and AU: 
Subject Rating (SR) (AFHA: SR)...............................................................................45 
7.2.3. 
Subject Global Impression of Severity (SGIS) ...........................................................46 
7.2.4. 
Alopecia Impact Assessment (AIA):  Subject Rating ................................................46 
7.2.5. 
Subject Global Impression of Change (SGIC) ...........................................................46 
7.2.6. 
Subject Global Impression of Treatment Satisfaction (SGITS) .................................46 
7.2.7. 
Subject Global Satisfaction with Hair Quality (SGSHQ) ...........................................46 
7.2.8. 
Dermatology Life Quality Index (DLQI) ...................................................................46 
7.3. 
Investigator Efficacy Assessments .............................................................................46 
7.3.1. 
Alopecia Scalp Appearance Assessment (ASAA) Clinician Rating (CR) .................47 
7.3.1.1. 
Alopecia Scalp Appearance Assessment (ASAA) for Patchy AA: Clinician 
Rating (CR) (ASAA-AAP: CR) .................................................................................48 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 14 of 90 
CONFIDENTAL 
 
  
 
7.3.1.2. 
Alopecia Scalp Appearance Assessment (ASAA) for AT and AU: Clinician 
Rating (CR) (ASAA-AT/AU: CR) .............................................................................48 
7.3.2. 
Alopecia Facial Hair Appearance Assessment (AFHA) for AA, AT and AU: 
Clinician Rating (CR) (AFHA: CR) ...........................................................................49 
7.3.3. 
Non-Scalp Hair Loss Assessment (NSHA) ................................................................51 
7.3.4. 
PHYSICIAN GLOBAL IMPRESSION OF SEVERITY (PhGIS) ............................51 
7.3.4.1. 
PHYSICIAN GLOBAL IMPRESSION OF SEVERITY (PhGIS-AAP) ...................52 
7.3.4.2. 
PHYSICIAN GLOBAL IMPRESSION OF SEVERITY (PhGIS-AT/AU) ...............52 
7.3.5. 
Physician Global Impression of Change (PhGIC) ......................................................52 
7.3.6. 
Hair Quality Assessments ...........................................................................................53 
7.3.6.1. 
Hair Pull Test ..............................................................................................................53 
7.3.7. 
Severity Alopecia Tool (SALT) Score .......................................................................53 
7.3.8. 
Alopecia Density and Extent Score (ALODEX) ........................................................53 
7.3.9. 
Vellus and Indeterminate Hair Assessment ................................................................53 
7.4. 
Photographic Assessment ...........................................................................................54 
8. 
ASSESSMENT OF SAFETY .....................................................................................55 
8.1. 
Safety Parameters .......................................................................................................55 
8.1.1. 
Demographic/Medical History/ Alopecia Areata History ..........................................55 
8.1.2. 
Vital Signs ..................................................................................................................55 
8.1.3. 
Physical Examination .................................................................................................55 
8.1.4. 
Electrocardiogram (ECG) ...........................................................................................56 
8.1.5. 
Clinical Laboratory Assessments ...............................................................................56 
8.1.6. 
Pregnancy Testing ......................................................................................................57 
8.1.7. 
Pharmacokinetic Assessments ....................................................................................58 
8.2. 
Adverse and Serious Adverse Events .........................................................................58 
8.2.1. 
Definition of Adverse Events .....................................................................................58 
8.2.1.1. 
Adverse Event (AE) ....................................................................................................58 
8.2.1.2. 
Serious Adverse Event (SAE) ....................................................................................58 
8.2.1.3. 
Unexpected adverse event ..........................................................................................59 
8.3. 
Reporting Adverse Events ..........................................................................................59 
8.3.1. 
Adverse event reporting period ..................................................................................59 
8.3.2. 
Severity .......................................................................................................................59 
8.3.3. 
Relationship to study medication ................................................................................59 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 15 of 90 
CONFIDENTAL 
 
  
 
8.3.4. 
Procedures for reporting adverse events .....................................................................60 
8.3.5. 
Procedure for reporting a serious adverse event .........................................................60 
8.4. 
PREGNANCY ............................................................................................................61 
8.4.1. 
Definition of Women of Child Bearing Potential (WOCBP) .....................................61 
8.4.2. 
Highly Effective Methods of Birth Control ................................................................61 
9. 
STATISTICS ..............................................................................................................63 
9.1. 
Sample Size and Power Calculations .........................................................................63 
9.2. 
Analysis Populations ..................................................................................................63 
9.3. 
Demographic and Baseline Characteristics ................................................................63 
9.4. 
Efficacy Analyses .......................................................................................................64 
9.4.1. 
Primary Efficacy Analyses .........................................................................................64 
9.4.2. 
Secondary Efficacy Analyses .....................................................................................64 
9.5. 
Safety Analyses ..........................................................................................................64 
9.6. 
Pharmacokinetic Analyses ..........................................................................................65 
10. 
TRAINING, DATA HANDLING AND RECORD KEEPING .................................66 
10.1. 
Training .......................................................................................................................66 
10.2. 
Data Collection ...........................................................................................................66 
10.3. 
Data Management .......................................................................................................66 
10.4. 
Study Monitoring ........................................................................................................66 
10.5. 
Source Documentation ................................................................................................67 
10.6. 
Inspection of Records .................................................................................................67 
10.7. 
Retention of Records ..................................................................................................67 
11. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................68 
12. 
ETHICS ......................................................................................................................69 
12.1. 
Ethics Review .............................................................................................................69 
12.2. 
Ethical Conduct of the Study ......................................................................................69 
12.3. 
Written Informed Consent ..........................................................................................69 
12.4. 
Study Conduct and Protocol Amendments .................................................................69 
12.5. 
Regulatory Documents ...............................................................................................70 
12.6. 
Contractual Requirements ..........................................................................................70 
13. 
LIST OF REFERENCES ............................................................................................71 
APPENDIX 1. ALOPECIA AREATA HISTORY .....................................................................73 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 16 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 2. FITZPATRICK’S SKIN TYPE CHART ...........................................................74 
APPENDIX 3. ALOPECIA SCALP APPEARANCE ASSESSMENT FOR PATCHY 
AA: SUBJECT RATING (ASAA-AAP:SR) ..............................................................75 
APPENDIX 4. ALOPECIA FACIAL HAIR APPEARANCE ASSESSMENT: 
SUBJECT RATING (AFHA:SR) ...............................................................................76 
APPENDIX 5. SUBJECT GLOBAL IMPRESSION OF SEVERITY FOR PATCHY 
AA (SGIS-AAP) .........................................................................................................78 
APPENDIX 6. ALOPECIA IMPACT ASSESSMENT ..............................................................79 
APPENDIX 7. SUBJECT GLOBAL IMPRESSION OF TREATMENT 
SATISFACTION FOR AA PATCHY (SGITS-AAP) ...............................................81 
APPENDIX 8. SUBJECT GLOBAL SATISFACTION WITH HAIR QUALITY 
(SGSHQ-AAP) ...........................................................................................................82 
APPENDIX 9. DERMATOLOGY LIFE QUALITY INDEX ....................................................83 
APPENDIX 10. ALOPECIA SCALP APPEARANCE ASSESSMENT FOR AT AND 
AU: SUBJECT RATING (ASAA-AT/AU:SR) .........................................................85 
APPENDIX 11. SUBJECT GLOBAL IMPRESSION OF SEVERITY FOR AT/AU 
(SGIS-AT/AU) ...........................................................................................................86 
APPENDIX 12. SUBJECT GLOBAL IMPRESSION OF TREATMENT 
SATISFACTION FOR AT/AU (SGITS-AT/AU)......................................................87 
APPENDIX 13. SUBJECT GLOBAL SATISFACTION WITH HAIR QUALITY FOR 
AT/AU (SGSHQ-AT/AU) ..........................................................................................88 
APPENDIX 14. SUBJECT GLOBAL IMPRESSION OF CHANGE (SGIC) ...........................89 
APPENDIX 15. STUDY MEDICATION INSTRUCTION SHEET .........................................90 
 
LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................17 
Table 2: 
Study Medication Interruption Criteria ......................................................................27 
Table 3: 
Schedule of Assessments ............................................................................................30 
Table 4: 
Investigational Product ...............................................................................................42 
Table 5: 
Subject Assessments ...................................................................................................45 
Table 6: 
Investigator Assessments ............................................................................................47 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 17 of 90 
CONFIDENTAL 
 
  
 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist 
Term 
Explanation 
AA 
Alopecia Areata 
AAP 
Alopecia Areata Patchy 
AE  
Adverse Event 
AFHA 
Alopecia Facial Hair Appearance Assessment 
AGA 
Androgenic Alopecia 
AIA 
Alopecia Impact Assessment 
ALADIN 
Alopecia Areata Disease Activity Index 
ALODEX 
Alopecia Density and Extent Score 
ALT 
Alanine aminotransferase 
ANOVA 
Analysis of Variance 
ASAA 
Alopecia Scalp Appearance Assessment 
AST 
Aspartate Aminotransferase 
AT 
Alopecia Totalis 
AU 
Alopecia Universalis 
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’s Rating 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
CTL 
Cytotoxic T-lymphocytes 
DLQI 
Dermatology Life Quality Index 
DMARDs 
Disease Modifying Anti-Rheumatic Drugs 
DPCP 
Diphenylcyclopropenone 
e.g.  
for example (Latin; exempla gratia) 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
°F 
Degrees Fahrenheit 
FACS 
Fluorescence Acquisition Cell Sorting 
FDA 
Food and Drug Administration 
G/g 
Gram 
GCP 
Good Clinical Practice 
HCl 
Hydrochloride 
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 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 18 of 90 
CONFIDENTAL 
 
  
 
Abbreviation or Specialist 
Term 
Explanation 
ICH 
International Conference on Harmonization  
i.e.  
that is (Latin; id est) 
IFN 
Interferon 
IHC 
Immunohistochemical  
IL 
Interleukin 
ITT 
Intent-to-Treat 
IRB 
Institutional Review Board 
JAK 
Janus Kinase  
KER 
Hair keratin panel 
KRT 
Hair Keratin 
LDH 
Lactate dehydrogenase 
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 
NMSC 
Nonmelanoma Skin Cancer 
OTC 
Over-The-Counter 
PDT 
Photodynamic Therapy 
PhGIC 
Physician Global Impression of Change 
PhGIS 
Physician 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 
SALT50 
50% Absolute Change in SALT (Hair Loss at Baseline – Hair loss At Follow-up) 
SALT50 
50% Change in Hair Loss or 50% regrowth 
SGIC 
Subject Global Impression of Change 
SGIS 
Subject Global Impression of Severity 
SGSHQ 
Subject Global Satisfaction with Hair Quality 
SGITS 
Subject Global Impression of Treatment Satisfaction 
SI 
Subject identifier 
SN 
Subject Number 
SOP 
Standard Operation Procedure 
SR 
Subject’s Rating 
STAT 
Signal Transducer and Activator of Transcription 
TEAE 
Treatment Emergent Adverse Event 
Th1 
Type 1 Helper T Cell 
TNK 
Tumor Necrosis Factor 
Tyk2 
Tyrosine Kinase 2 
UPT 
Urine Pregnancy Test 
US 
United States 
UVA 
Ultraviolet A  
UVB 
Ultraviolet B 
WOCBP 
Women of childbearing potential  


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 19 of 90 
CONFIDENTAL 
 
  
 
1. 
INTRODUCTION 
Aclaris Therapeutics, Inc. is developing ATI-501 for the treatment of alopecia areata, alopecia 
universalis, and alopecia totalis.  ATI-501 is a potent highly selective inhibitor of Janus kinase 1 
(JAK1) and Janus kinase 3 (JAK3). 
1.1. 
Overview of Alopecia Areata 
Alopecia areata (AA) is an autoimmune dermatologic condition, which, in its mildest form, is 
typically characterized by patchy non-scarring hair loss on the scalp and/or body.  More severe 
forms of AA include total scalp hair loss, known as alopecia totalis (AT), and total loss of all the 
hair on the scalp and body- importantly, including loss of eyebrows, eyelashes, and intranasal 
hair- known as alopecia universalis (AU).  While spontaneous regrowth of hair is common in the 
milder form of AA (patchy), where the hair loss may wax and wane, in patients with the 
extensive hair loss of AT or AU, spontaneous hair regrowth is rare.  AA affects both males and 
females across all ethnic groups and ages, and 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 diphenylcyclopropenone 
(DPCP), squaric acid dibutyl ester (SADBE), or treatment with topical anthralin.  While these 
same treatment options may be utilized for the more severe forms of AA, their use in the more 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 20 of 90 
CONFIDENTAL 
 
  
 
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. 
1.2. 
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 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 21 of 90 
CONFIDENTAL 
 
  
 
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.  Interferons, as key activators of the MHC locus and of the 
cellular immune response, appear to play a key role in eliminating the immunologic privilege of 
the hair follicle and in inducing and maintaining the pathologic inflammatory response in AA.  
This is also seen in the C3H-HeJ mouse model of AA, in which IFN-γ is required for 
pathogenesis, and in which administration of IFN-γ accelerates disease. (Gilhar 2005, Hirota 
2003). 
AA has been viewed as a Th1-driven disease and, consistent with a pathogenic cellular immune 
response, elevated Th1 cytokines/ chemokines (IFN-induced chemokines [IP-10/CXCL10]) are 
seen in the peripheral blood of AA patients and IFN-inducible gene signatures have been 
described in the skin of AA patients and may correlate with disease activity (Arca 2004, 
Barahmani 2009, Kuwano 2007).  Additionally, transcriptional profiles in human AA patients 
have shown a Type I IFN response in lesional biopsies and Th1 skewing and elevated IFN 
response cytokines/chemokines in both the peripheral blood and in reviewed scalp biopsies 
(Jabbari 2015, Xing 2014, Jabbari 2016).  The cellular source of IFN-γ is hypothesized to be the 
T-cells, as in the AA mouse model IFN-gamma producing CD8+NKG2D+ cells dominate the 
dermal hair follicle infiltrate, and in human AA, IFN-γ producing cells were identified in 4 of 5 
dermal crawl-out assays (Christiano 2016).  Additionally, data implicate IL- 15 in driving 
activation of IFN-producing CD8 T-cells (Xing 2014).  
Thus, preclinical and preliminary clinical information, as discussed above, strongly suggests that 
the primary pathophysiologic mechanism in AA (including AT and AU) is a cytokine mediated 
(primarily through T-lymphocyte induced upregulation of IL-15 and IFN gamma) induction of 
and prolonged maintenance of the telogen stage of the hair cycle.  Inhibitors of the JAK/STAT 
pathway, particularly JAK1 and JAK3, are known to downregulate the effects of both IFN-
gamma (through the inhibition at JAK1), and IL-15 (through inhibition at both JAK1 and JAK 
3), and several published case reports have demonstrated the potential for compounds that are 
JAK1/3 inhibitors to induce hair growth in patients with AA (Kim 2017, Craiglow 2014 and 
2017, Gupta 2016, Scheinberg 2016).  As ATI-501 is a potent inhibitor at JAK 1 and JAK 3, it is 
strongly suggested that ATI-501 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-501 as a treatment 
for stable patchy AA, AU or AT.  ATI-501 is an oral prodrug that is rapidly converted 
presystemically to ATI-502, a potent highly selective inhibitor of Janus kinase 1 (JAK1) and 
Janus kinase 3 (JAK3).  This study will evaluate whether or not the orally administered 
JAK1/JAK3 inhibitor prodrug, ATI-501, 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. 
1.3. 
Previous Clinical Study Experience with ATI-501 
Eight Phase 1 clinical studies were conducted with ATI-501 oral doses ranging from single 
ascending doses of ATI-501 of 50 mg to 500 mg and multiple ascending doses of 200, 400 mg, 
600 mg and 800 mg BID for 14 days. A total of 186 healthy volunteers were exposed to oral 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 22 of 90 
CONFIDENTAL 
 
  
 
doses of ATI-501.  Single and twice-daily doses of ATI-501 were well-tolerated.  There were no 
SAEs reported in the eight completed clinical studies.   
In study ATI-50001-AUAT-106, the multiple ascending dose study, 54 subjects received doses 
up to 800 mg BID for 14 days.  The most frequently reported treatment related adverse events 
(TRAE) reported in more than 1 subject were:  headache (14.8%), abdominal discomfort (9.3%), 
decreased appetite (9.3%), dizziness (7.4%), somnolence (7.4%), diarrhea (5.6%), dry skin 
(5.6%), nausea (5.6%), constipation (3.7%), dyspepsia (3.7%), feeling hot (3.7%) and paresthesia 
(3.7%). 
No clinically significant laboratory abnormalities were observed.  There were no clinically 
significant findings from 12-lead ECGs.  One subject experienced a transient elevation in blood 
pressure (pre-dose 126/85mmHg, 4 hours post dose 142/104 mm/Hg) which was assessed as 
clinically significant by the investigator.  The subjects blood pressure returned to within normal 
limits at all other assessed timepoints throughout the study.   There were no other clinically 
significant findings from vital signs assessments.   
In study, ATI-50001-AUAT-106, ATI-501 was not detected in plasma and there was a dose-
related increase in plasma of the active metabolite ATI-502.  Systemic levels of ATI-502, 
following oral doses of ATI-501 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-501 support the oral 
administration of ATI-501 (ATI-501 Investigator Brochure).   
1.4. 
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-501 is a potent inhibitor at 
JAK 1 and JAK 3, it is strongly suggested that ATI-501 may be effective in the treatment of AA.   
This study will evaluate the safety, tolerability and efficacy of ATI-501 Oral Suspension, 400 
mg, 600 mg, or 800 mg compared to Placebo Oral Suspension taken with food, twice-daily for 
24 weeks.   
Subjects with hair loss due to AA, AU or AT ranging from 30% to 100% 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 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 23 of 90 
CONFIDENTAL 
 
  
 
surface area from the SALT I diagram into 1% scalp surface areas and allows the investigator to 
assign a 10-point density rating to each area from 0 = no hair loss to 10 = 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 and exploratory 
endpoints.   
Subjects will be enrolled with 30% to 100% hair loss over the entire scalp surface area based on 
the SALT score at Screening (Visit 1) and Baseline (Visit 2).  Screening (Visit 1) and Baseline 
(Visit 2) ALODEX scores 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 (Visit 2).  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 (Visit 2).  
Subjects with patchy AA will have ClinRO and PRO assessments completed for a scalp target 
patch and for scalp hair loss over the subject’s whole 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.   
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 24 of 90 
CONFIDENTAL 
 
  
 
2. 
TRIAL OBJECTIVES AND ENDPOINTS 
2.1. 
Primary Objective 
The primary objective is to assess the safety, tolerability and efficacy of ATI-501 Oral 
Suspension, 400 mg, 600 mg, or 800 mg compared to Placebo Oral Suspension in subjects with 
alopecia areata (AA), alopecia universalis (AU) or alopecia totalis (AT). 
2.2. 
Secondary Objectives 
Secondary objectives are: 
• 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 
• To assess the level of ATI-502 in the blood at trough 
2.3. 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the mean percent change from Baseline in the Severity of 
Alopecia Tool (SALT) score at Week 24 (Visit 9).   
2.4. 
Secondary Efficacy Endpoints 
 
• 
Mean percent change from Baseline in the Alopecia Density and Extent Score (ALODEX) 
score at Week 24. 
• 
Change from Baseline in the SALT score at Week 24 (Visit 9) with additional analyses at 
each applicable post-baseline visit where data are available. 
• 
Change from Baseline in the Alopecia Density and Extent Score (ALODEX) score at Week 
24 (Visit 9) with additional analyses at each applicable post-baseline visit where data are 
available. 
• 
Proportion of subjects in each treatment arm achieving at least a 50% reduction in ALODEX 
score at Week 24 (Visit 9) with additional analyses at each applicable post-baseline visit 
where data are available compared to Baseline. 
• 
Proportion of subjects in each treatment arm achieving at least a 50% reduction in SALT 
score at Week 24 (Visit 9) with additional analyses at each applicable post-baseline visit 
where data are available compared to Baseline. 
• 
Change from Baseline in the Alopecia Scalp Appearance Assessment (ASAA) (Patient-
reported outcome [PRO]) at Week 24 (Visit 9) with additional analyses at each applicable 
post-baseline visit where data are available. 
• 
Change from Baseline in the Alopecia Scalp Appearance Assessment (ASAA) (Clinician-
reported outcome [ClinRO]) at Week 24 (Visit 9) with additional analyses at each applicable 
post-baseline visit where data are available. 
• Change from Baseline in the Physician Global Impression of Severity (PhGIS) at Week 24 
(Visit 9) with additional analyses at each applicable post-baseline visit where data are 
available. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 25 of 90 
CONFIDENTAL 
 
  
 
• 
Change from Baseline in Alopecia Facial Hair Appearance Assessment (AFHA) (Clinician 
and Subject) at Week 24 (Visit 9) with additional analyses at each applicable post-baseline 
visit where data are available. 
• 
Change from Baseline in the Subject Global Impression of Severity (SGIS) at Week 24 (Visit 
9) with additional analyses at each applicable post-baseline visit where data are available. 
• 
Change from Baseline in the subject reported Alopecia Impact Assessment (AIA) at Week 24 
(Visit 9) with additional analyses at each applicable post-baseline visit where data are 
available. 
• 
Subject Global Impression of Treatment Satisfaction (SGITS) at Week 24 (Visit 9) with 
additional analyses at each applicable post-baseline visit where data are available. 
• 
Change from Baseline in the Subject Global Satisfaction with Hair Quality (SGSHQ) at Week 24 
(Visit 9) with additional analyses at each applicable post-baseline visit where data are available. 
• 
Change in Dermatology Life Quality Index (DLQI) total score between Baseline and Week 
24 (Visit 9) with additional analyses at each applicable post-baseline visit where data are 
available. 
• 
Global Impression of Change (Clinician and Subject) at Week 24 (Visit 9). 
 
2.5. 
Other Assessments 
• Hair quality assessment including normalization of exclamation point hairs and hair 
shedding will be described. 
• Vellus and Indeterminate scalp hair will be described. 
• Non-scalp hair assessments (body and nasal hair) will be described. 
2.6. 
Pharmacokinetic Endpoints 
The concentration of ATI-502 in the blood predose at Visit 2 and at trough at Visit 4, Visit 6 and 
Visit 9 will be measured by a bioanalytical lab using fully validated analytical methods.  
2.7. 
Safety Endpoints 
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. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 26 of 90 
CONFIDENTAL 
 
  
 
3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design 
This Phase 2, multicenter, randomized, double-blind study is designed to evaluate the safety, 
tolerability and efficacy of ATI-501 Oral Suspension in subjects with AA, AU or AT.  Subjects 
will be required to have a clinical diagnosis of stable AA, AU or AT with 30% to 100% total 
scalp hair loss for a duration of at least 6 months up to and including 12 years (inclusive).  Stable 
AA, AU or AT is defined as no areas of spontaneous terminal scalp hair growth. 
During the screening period, subjects will be assessed for eligibility into the study.  Subjects will 
receive ATI-501 Oral Suspension, 400 mg, 600 mg, or 800 mg or Placebo Oral Suspension 
twice-daily for up to 24 weeks. Assessment of response to treatment will be performed at Week 
4, Week 8, Week 12, Week 16, Week 20, Week 24, and post-treatment Week 28.  Safety and 
tolerability will be evaluated at each study visit by assessment of adverse events, clinical 
laboratory tests, and vital signs, and at select visits, ECGs. 
 
Subjects who complete study visits through Visit 9 will have the option to roll over into an open-
label study ATI-502-AA-203.  Subjects who withdraw consent or meet study medication 
discontinuation criteria (Section 3.4.1.2) on study ATI-501-AUAT-201 will not be eligible for 
roll-over to study ATI-502-AA-203.  Subjects who complete the assessments for Visit 9 and then 
meet study ATI-502-AA-203 entry criteria and provide written consent will skip post-treatment 
Visit 10.   Subjects who are not eligible for ATI-502-AA-203 or who decline to participate 
should return for the final Visit 10 assessments. 
3.2. 
Number of Subjects 
A total of approximately 95 subjects will be enrolled at approximately 25 US sites. 
3.3. 
Treatment Assignment 
Subjects will be randomized 1:1:1:1 to ATI-501 Oral Suspension 400 mg, 600 mg, 800 mg or 
Placebo Oral Suspension twice-daily for 24 weeks followed by a 4-week post-treatment follow 
up period. 
3.4. 
Dose Adjustment Criteria 
Subjects should not modify the study medication dosage or frequency without the investigator’s 
prior approval. All study medication modifications must be reported on the appropriate eCRF.  If 
study medication intolerance or safety issue occurs, after consulting with the Aclaris 
Therapeutics, Inc. Medical Monitor (see page 1), the investigator or designee may direct the 
subject to modify the study medication frequency from twice-daily to once-a-day. If the subject 
cannot take the study medication twice-daily for more than 4 consecutive days, other dose 
modifications and continuation in the study must be reviewed with the Medical Monitor. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 27 of 90 
CONFIDENTAL 
 
  
 
3.4.1. 
Safety Criteria for Adjustment or Stopping Doses 
3.4.1.1. 
Study Medication Interruption 
Treatment with ATI-501 Oral Suspension should be temporarily interrupted in the event of 
severe adverse events considered related to ATI-501, or in the event of one or more of the 
abnormal laboratory values listed in Table 2.  
 
Table 2: Study Medication Interruption Criteria 
Laboratory Test 
Hold Study Medication if: 
Resume Study Medication if: 
WBC count 
< 2 x 103/µL 
≥ 2.5 x 103/µL 
ANC 
< 1 x 103/µL 
≥ 1.5 x 103/µL 
Lymphocyte count < 0.5 x 103/µL 
≥ 0.75 x 103/µL 
Platelet count 
< 75 x 103/µL 
Returns to Baseline values 
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 
 
Subjects with one or more of the Screening (Visit 1) laboratory values meeting the Study 
Medication Interruption Criteria found in Table 2 must have repeat lab testing performed with 
results meeting the minimum criteria for resumption in order to initiate treatment at Baseline 
(Visit 2).   
 
During treatment, 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 dosing. 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) returns to normal or to 
Baseline values.    
3.4.1.2. 
Study Medication Discontinuation 
Study medication should be permanently discontinued in the event of any of the following: 
• Subject’s study medication blinding is broken 
• Severe infection requiring parenteral antimicrobial therapy or hospitalization 
• Symptomatic herpes zoster 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 28 of 90 
CONFIDENTAL 
 
  
 
• Malignancy  
• Anaphylactic or severe allergic reaction 
• WBC Count: < 1 x 103/µL or second occurrence of < 2 x 103/µL  
• ANC: < 0.5 x 103/µL or second occurrence of < 1 x 103/µL  
• Lymphocyte count: < 0.3 x 103/L or second occurrence of < 0.5 x 103/µL  
  
• Platelet count: < 50 x 103/µL or second event of < 75 x 103/µL – in each case, value should 
be confirmed by retesting before treatment discontinuation 
• Hemoglobin: < 6.5 g/dL or second occurrence of < 8 g/dL – in each case, value should be 
confirmed by retesting before treatment discontinuation 
• AST or ALT:  
o > 5 x ULN persisting for 2 weeks of study medication interruption or second 
event of > 5 x ULN 
o > 3 x ULN with total bilirubin >2 x ULN or symptoms of hepatocellular  
injury [fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, 
rash and/ or eosinophilia (>5%)].  
 
• 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. 
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 screening.  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. 
3.5. 
Criteria for Study Termination 
This study may be terminated prematurely in whole or in part due to a change in the benefit/risk 
profile for ATI-501 Oral Suspension 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 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 29 of 90 
CONFIDENTAL 
 
  
 
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-501 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. 
3.6. 
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 (Table 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.      


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 30 of 90 
CONFIDENTAL 
 
  
 
Table 3: 
Schedule of Assessments 
 
Screening 
Baseline 
Treatment 
Post-Treatment 
Visit 1 
Visit 2 
 
Visit 31 
 
Visit 4 
 
Visit 5 
 
Visit 6 
 
Visit 7 
Visit 8 
 
Visit 9 
(ET) 
 
Visit 1019 
 
Week 
 
0 
2 
4 
8 
12 
16 
20 
24 
28 
Treatment Day 
-30 to 0 
1 
15 
29 
57 
85 
113 
141 
169 
197 
Treatment Window(days) 
N/A 
N/A 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Informed consent2 
X 
 
 
 
 
 
Inclusion/exclusion criteria  
X 
X 
 
 
 
 
 
 
 
 
Physical exam3 
X 
 
 
 
 
 
 
X 
 
Demographics & medical 
history 
X 
 
 
 
 
 
 
 
 
 
Alopecia Areata History  
X 
 
 
 
 
 
 
 
 
 
Vital signs4  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical CBC, Chemistry, 
Virology, Serum Pregnancy, 
Urinalysis5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for PK (Select Sites 
Only)6 
 
X  
(Pre-dose) 
 
X 
 
X 
 
 
X 
 
Urine pregnancy test7 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
ECG  
X 
 
X 
 
 
 
 
 
X 
 
Subject8 
Target Patch 
identification (Patchy 
AA Subjects Only) 
 
X 
 
 
 
 
 
 
 
 
Alopecia Scalp 
Appearance 
Assessment (ASAA-
AAP: SR or ASAA-
AT/AU: SR) 9  
 
X 
X 
 
 
X 
 
 
X 
X 
Alopecia Facial Hair 
Appearance 
Assessment (AFHA: 
SR) 
 
X 
X 
 
 
X 
 
 
X 
X 
Subject Global 
Impression of Severity 
(SGIS-AAP or SGIS-
AT/AU)  
 
X 
X 
 
 
X 
 
 
X 
X 
Alopecia Impact 
Assessment (AIA):  
Subject Rating 
 
X 
X 
 
 
X 
 
 
X 
X 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 31 of 90 
CONFIDENTAL 
 
  
 
 
Screening 
Baseline 
Treatment 
Post-Treatment 
Visit 1 
Visit 2 
 
Visit 31 
 
Visit 4 
 
Visit 5 
 
Visit 6 
 
Visit 7 
Visit 8 
 
Visit 9 
(ET) 
 
Visit 1019 
 
Week 
 
0 
2 
4 
8 
12 
16 
20 
24 
28 
Treatment Day 
-30 to 0 
1 
15 
29 
57 
85 
113 
141 
169 
197 
Treatment Window(days) 
N/A 
N/A 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Subject Global 
Impression of Change 
(SGIC) 
 
 
 
 
 
 
 
 
X 
 
Subject Global 
Impression Treatment 
Satisfaction (SGITS-
AAP or SGITS-
AT/AU)10 
 
 
 
 
 
X 
 
 
X 
X 
Subject Global 
Satisfaction with Hair 
Quality (SGSHQ-
AAP or SGSHQ-
AT/AU) 
 
X 
X 
 
 
X 
 
 
X 
X 
DLQI11 
 
X 
X 
 
 
X 
 
 
X 
X 
Investigator12 
Alopecia Scalp 
Appearance 
Assessment (ASAA: -
AAP:CR of ASAA-
AT/AU:CR)13  
 
X 
X 
 
 
X 
 
 
X 
X 
Alopecia Facial Hair 
Appearance 
Assessment (AFHA: 
CR) 
 
X 
X 
 
 
X 
 
 
X 
X 
Non-Scalp Hair Loss 
Assessment (NSHA) 
 
X 
X 
 
 
X 
 
 
X 
X 
Physician Global 
Impression of Severity 
(PhGIS-AAP or 
PHGIS-AT/AU) 
 
X 
X 
 
 
X 
 
 
X 
X 
Physician Global 
Impression of Change 
(PhGIC) 
 
 
 
 
 
 
 
 
X 
 
Hair Quality 
Assessment (Patchy 
AA Subjects Only) 
 
X 
 
 
 
X 
 
 
X 
X 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 32 of 90 
CONFIDENTAL 
 
  
 
 
Screening 
Baseline 
Treatment 
Post-Treatment 
Visit 1 
Visit 2 
 
Visit 31 
 
Visit 4 
 
Visit 5 
 
Visit 6 
 
Visit 7 
Visit 8 
 
Visit 9 
(ET) 
 
Visit 1019 
 
Week 
 
0 
2 
4 
8 
12 
16 
20 
24 
28 
Treatment Day 
-30 to 0 
1 
15 
29 
57 
85 
113 
141 
169 
197 
Treatment Window(days) 
N/A 
N/A 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
SALT Score (prior to 
ALODEX)14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ALODEX Score (after 
SALT)15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vellus and 
Indeterminate Hair 
Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Photography (complete scalp)  
 
X 
 
X 
X 
X 
X 
X 
X 
 
Subject randomization 
 
X 
 
 
 
 
 
 
 
 
Subject instructions16 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Dispense study medication17  
 
X 
X18 
X 
X 
X 
X 
X 
 
 
Collect study medication and 
assess compliance 17  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant therapies 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations:  CR= Clinician Rating; ET= Early termination Visit; SR= Subject Rating 
1Efficacy assessments completed at Visit 3 are to test the reliability of the clinician and patient reported outcome tools.  
2A written, signed ICF 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). 
3 A physical exam includes: general appearance, examination of head, eyes, ears, nose and throat, respiratory, cardiovascular, abdominal, neurological, musculoskeletal, 
extremities, lymphatic and skin assessment (other than AA). 
4Vitals signs include: oral or ear temperature, blood pressure, heart rate, respiration rate (height and weight at Screening only). 
5 Clinical laboratory non-fasting sampling includes: CBC, Chemistry with lipids, Urinalysis.  Quantiferon Gold, HIV, Hepatitis B and C, TIBC, Serum Iron, Serum Ferritin, 
T3, free T4, TSH and Serum Pregnancy should be done at screening visit only.   
6 At  Select sites:  A single 4.5 mL sodium citrate vacutainer should be drawn at Visit 2 (predose) and Visits 4, 6, and 9, 12 hours (± 30 minutes) after the prior evening 
dose.  Subjects participating in the PK analysis should be called the day prior to Visit 4, 6, and 9 to remind them to take their evening dose approximately 11 hours prior to 
the visit time and to document the time of the evening dose. 
7 Subjects who are WOCBP should have a urine pregnancy test (UPT) performed early in the screening procedures (following informed consent) which shows negative 
results in order to avoid the continuation of what would then be unnecessary screening testing.  Subjects who are WOCBP must also have a negative serum pregnancy test 
result from Screening (Visit 1) to continue in the study, and a negative UPT at Baseline (Visit 2) prior to randomization.  UPTs in WOCBP must also be obtained at Visits 4, 
5, 6, 7, 8, 9 and 10 and must be negative for the subject to continue in the study.   
8 The subject should perform assessments prior to the Investigator assessments.  The investigator may assist the subject in locating a Target Patch. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 33 of 90 
CONFIDENTAL 
 
  
 
 
Screening 
Baseline 
Treatment 
Post-Treatment 
Visit 1 
Visit 2 
 
Visit 31 
 
Visit 4 
 
Visit 5 
 
Visit 6 
 
Visit 7 
Visit 8 
 
Visit 9 
(ET) 
 
Visit 1019 
 
Week 
 
0 
2 
4 
8 
12 
16 
20 
24 
28 
Treatment Day 
-30 to 0 
1 
15 
29 
57 
85 
113 
141 
169 
197 
Treatment Window(days) 
N/A 
N/A 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
9 Subjects with 30% to 95% scalp hair loss will identify the most bothersome patchy area at Baseline (Visit 2). A score of “no hair” or “a little hair” in the target patch is 
required. For subjects with AU or AT, the target patch identification at Baseline (Visit 2) will be recorded as “Not Applicable” in the source document and eCRF. 
10 The study staff should remind the subject that this question is in relation to the satisfaction with the result of the hair regrowth. 
11 The study staff should remind the subject that the questions are in relation to hair loss and not skin. 
12 Investigator assessments should be performed after the Subject Assessments.   
13 In subjects with patchy AA, the assessment of hair quality will be performed at the edge of the target patch.  For subjects with AU/AT, the assessment of hair quality will 
be recorded as Not Applicable in the source document and eCRF. At Baseline (Visit 2), the assessment should be determined prior to the first dose of study medication. 
14 SALT score must be determined prior to ALODEX using device provided.  
15ALODEX score determined after SALT score using device provided. 
16 The study staff must instruct the subject to dose study medication according to the instructions in Appendix 15. 
17Staff should review the usage based on the number of used and unused bottles and counsel the subject as necessary. 
18At Visit 3, the subject’s Month 1 drug supply carton should be reviewed by site staff as part of compliance activities and then released back to the subject for continued 
use. 
19 Subjects who complete study visits through Visit 9 will have the option to roll over into an open-label study ATI-502-AA-203.  Subjects who withdraw consent or meet 
study medication discontinuation criteria (Section 3.4.1.2) on study ATI-501-AUAT-201 will not be eligible for roll-over to study ATI-502-AA-203.  Subjects who 
complete the assessments for Visit 9 and then meet study ATI-502-AA-203 entry criteria and provide written consent will skip post-treatment Visit 10.   Subjects who are 
not eligible for ATI-502-AA-203 or who decline to participate should return for the final Visit 10 assessments. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 34 of 90 
CONFIDENTAL 
 
  
 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
Male and female subjects, 18 years of age or older, with a clinical diagnosis of stable AA, AU or 
AT of the scalp, who meet all the inclusion criteria and none of the exclusion criteria, will be 
eligible to enroll in this study.  
4.1. 
Subject Inclusion Criteria 
 
Subjects must meet the following criteria to be eligible for participation in the study: 
1. Able to comprehend and willing to sign an Informed Consent Form (ICF). 
2. Male or non-pregnant, non-nursing female ≥ 18 years old at the time of informed consent. 
3. Have a clinical diagnosis of stable AA, AU or AT (Stable is defined as no current areas 
of spontaneous terminal scalp hair regrowth). 
4. Have a Severity of Alopecia Tool (SALT) score of at least 30% to 100% total scalp hair 
loss determined by the study investigator at Screening (Visit 1) and Baseline (Visit 2). 
5. Subjects with 30% to 95% scalp hair loss (based on SALT score) must 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 (ASAA).  The target patch 
is defined as the most bothersome patchy area of hair loss as identified by the subject 
(Refer to Section 7.1). 
6. Have a duration of the current episode of stable scalp hair loss for a minimum of 6 
months and a maximum duration of hair loss of 12 years (inclusive). [Current episode is 
defined as the period of the current presentation of hair loss (AA, AU or AT)]. 
7. If the subject is a woman of childbearing potential (WOCBP), she must have: 
•  Negative serum pregnancy tests at Screening (Visit 1); and 
•  A negative urine pregnancy test at Baseline (Visit 2); and  
• Agree to not be planning a pregnancy during the study duration and use a highly 
effective method of contraception during the study and for 30 days after the last 
dose of study medication. (Refer to Section 8.4.2). 
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 and hair dyeing throughout the study period. 
Subjects who shave their scalp must be willing to refrain from shaving their scalp for at 
least two weeks prior to each study visit, as determined by the investigator based on the 
ability to assess 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 a 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 a maintenance dose throughout the study.  


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 35 of 90 
CONFIDENTAL 
 
  
 
13. Sexually active male subjects must agree to use a barrier method of contraception with 
any WOCBP partner(s) from the first dose of study medication to at least 30 days after the 
last dose of study medication. 
4.2. 
Subject 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 dose of study medication.  
2. Diffuse alopecia areata. [Diffuse alopecia areata is defined as the absence of the typical 
patchy distribution of hair loss (in subjects with <95% total scalp hair loss) with hair 
thinning distributed throughout the scalp.] 
3. Concomitant hair loss disorder (by history or physical exam) such as androgenetic 
alopecia (AGA) or scarring alopecia (e.g., cicatricial alopecia, frontal fibrosing alopecia, 
etc.). Subjects without a prior known history of 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 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, AU or AT 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 autoimmune, metabolic, 
hepatic, endocrine, renal, gastrointestinal, pulmonary, cardiovascular, genitourinary, or 
hematological disease, neurologic or cerebral disorders, 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 (e.g. 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. Refer to Exclusion 
Criterion 12 for herpes zoster, herpes simplex, or cytomegalovirus infections.   
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 (HepB surface Ab without the presence of Hep B surface Ag) will be allowed 
to participate. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 36 of 90 
CONFIDENTAL 
 
  
 
12. History of recurrent herpes zoster (more than one episode) or disseminated herpes zoster 
(a single episode) or disseminated herpes simplex (single episode) 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. [Subjects with any 
Screening laboratory values meeting the Study Medication Interruption Criteria found in 
Table 2 must have repeat lab testing performed with results meeting the minimum criteria 
for resumption in order to initiate treatment at Baseline (Visit 2)]. 
14. Subjects with absolute neutrophil count <1,800/µL, or platelet count <130,000/µL. 
15. Subjects who have received any of the following treatments for the timeframes specified 
below: 
• 
Disease Modifying Anti-Rheumatic Drugs (DMARDS), Biologics or 
immunosuppressants, including but not limited to: anakinra, adalimumab, 
azathioprine, corticosteroids, cyclosporine, etanercept, infliximab, methotrexate, TNF 
inhibitors, ustekinumab within 1 month or 5 half-lives (whichever is greater) of 
Baseline (Visit 2). 
• 
Plaquenil within 2 months of Baseline (Visit 2). 
• 
JAK inhibitors (oral or topical) within 6 months of Baseline (Visit 2). 
• 
Intralesional steroids or platelet rich plasma injections in the scalp within 1 month of 
Baseline (Visit 2). 
• 
Topical treatments on the scalp with anthralin, bimatoprost, corticosteroids, 
diphencyprone, diphenylcyclopropenone (DPCP), squaric acid dibutylester (SADBE), 
minoxidil, pimecrolimus, or tacrolimus within 1 month of Baseline (Visit 2). 
• 
Phototherapy (narrow band Ultraviolet B [NB UVB] or broadband therapy) within 4 
weeks of Baseline (Visit 2). 
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 Baseline (Visit 2).   
17. Any condition possibly affecting oral drug absorption, e.g., gastrectomy, clinically 
significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric 
bypass.  Procedures such as gastric banding are not exclusionary. 
18. Sensitivity to any of the ingredients in the study medications. 
19. Unwillingness to refrain from weaves, hair extensions, or shaving of the scalp for at least 
two weeks prior to a study visit, at the discretion of the investigator, based on the ability 
to assess hair growth.  
20. Screening ECG findings of: 
• QTcF >450msec for males or >470msec for females (use of the ECG algorithm is 
acceptable for this purpose) 
• 
Heart rate ≤45 or ≥ 100 beats/minutes (A subject with a heart rate < 45 beats/min may 
be enrolled if in the opinion of the investigator the heart rate is not clinically 
significant).  
• Rhythm disturbance other than sinus arrhythmia or ectopic supraventricular 
rhythm (ectopic atrial rhythm) 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 37 of 90 
CONFIDENTAL 
 
  
 
• 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 
21. Vaccination with a live or attenuated vaccine within 6 weeks prior to Baseline (Visit 2) or 
planned vaccinated with these vaccines at any time during treatment or within 6 weeks 
following discontinuation of study medication.  
22. Participation in an investigational study with ATI-502 Topical Solution.  
23. Subjects unwilling to have photographs taken for study purposes.  
4.3. 
Subject Withdrawal Criteria 
Subjects will be informed that they are free to withdraw from the study at any time and for any 
reason. The investigator may remove a subject from the study if, in the investigator’s opinion, it 
is not in the best interest of the subject to continue the study. Examples of other reasons subjects 
may be discontinued from the study are: a change in compliance with an inclusion or exclusion 
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 (Refer to Section 3.5 for study medication discontinuation or termination criteria).  
In case of premature discontinuation from study participation, all efforts will be made to perform 
all Week 24 (Visit 9) 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. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 38 of 90 
CONFIDENTAL 
 
  
 
5. 
TREATMENT OF SUBJECTS 
5.1. 
Study Medication Administration 
Study medication will be self-administered by the subject.  Study staff should instruct the subject 
not to take study medication on an empty stomach.  Subjects will be instructed to take one 
single-dose bottle of study medication followed by a full glass of water, within approximately 30 
minutes after the morning meal and after approximately 8 to 12 hours, to take the second dose 
within approximately 30 minutes after the evening meal as detailed in study medication 
instructions in Appendix 15.  Subjects should not mix/dilute the medication in other liquids, 
rather they should take the study medication as indicated in the directions provided. 
The investigational site staff will dispense a sufficient supply of study medication at the visits  
detailed in the Schedule of Assessments (Table 3) and will review the study medication 
instructions as detailed in Appendix 15.  The investigational site staff dispensing and reconciling 
the study medication should not be involved in the investigator or subject efficacy assessments. 
Subjects will be given a compliance record to complete.  At each study visit, subjects should bring 
the study medication including used and unused bottles and the completed compliance record.  The 
study staff will review the compliance record, used and unused bottles and the study medication 
instructions.  
5.2. 
Concomitant Medications 
Concomitant therapies are any new or existing therapies received from Screening (Visit 1) until 
discharge from the study.  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 reviewed by the investigator and will not affect efficacy or safety.  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 and are not used for hair growth in other areas. Inhaled or intranasal corticosteroids are 
allowed in the study. 
Prior permitted concomitant medications taken within 30 days of beginning treatment with ATI-
501 Oral Suspension will be documented in the subject’s source document and eCRF.  In 
addition, any new permitted medications administered during protocol treatment and through 
Week 28 (Visit 10) will be documented in the subject’s source document and eCRF.   


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 39 of 90 
CONFIDENTAL 
 
  
 
5.3. 
Grooming 
Routine shaving of beard or body hair is allowed during the study as long as the subject refrains 
from shaving for a period sufficient to show hair growth prior to Visits 6, 9, and 10.  Shaving of 
the scalp must conform to the requirements specified in Inclusion Criterion #9.  Subjects are 
allowed to grow their hair longer than the length at baseline visit, as long as the investigator can 
assess hair loss and regrowth during the study and hair regrowth is pinned out of the way to show 
the areas with hair loss at baseline for photographs.   
5.4. 
Prohibited Medications 
Any medication, shampoo or hair product known to affect hair growth in AA, AU or AT 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.   
The following medications and therapies require a specific washout period prior to study entry 
and are not permitted during the study:   
• Disease Modifying Anti-Rheumatic Drugs (DMARDS), Biologics or 
immunosuppressants, including but not limited to: anakinra, adalimumab, azathioprine, 
corticosteroids, cyclosporine, etanercept, infliximab, methotrexate, TNF inhibitors, 
ustekinumab within 1 month or 5 half-lives (whichever is greater) of Baseline (Visit 2). 
• Plaquenil within 2 months of Baseline (Visit 2). 
• JAK inhibitors (oral or topical) within 6 months of Baseline (Visit 2). 
• 
Intralesional steroids or platelet rich plasma treatment in the scalp within 1 month of 
Baseline (Visit 2). 
• 
Topical treatments on the scalp with anthralin, bimatoprost, corticosteroids, 
diphencyprone, diphenylcyclopropenone (DPCP), squaric acid dibutylester (SADBE), 
minoxidil, pimecrolimus, or tacrolimus within 1 month of Baseline (Visit 2). 
• 
Phototherapy (narrow band Ultraviolet B [NB UVB] or broadband therapy) within 4 
weeks of Baseline (Visit 2). 
 
Any prohibited medications taken by a subject in violation of the protocol requirements will be 
documented in the source record and eCRF.  Discussion with the Sponsor’s Medical Monitor 
must also take place in order to determine if the subject’s continuation in the study is allowed. 
5.5. 
Vaccine Guidelines 
Vaccination with live or attenuated components is prohibited during the study and for 6 weeks 
after the last dose of study medication.  Similarly, current routine household contact with 
children and others vaccinated with live or attenuated vaccine components should be avoided 
during treatment and for 6 weeks following completion of the study.  Some of these vaccines 
include varicella (“chickenpox”) vaccine, oral polio vaccine, and the inhaled flu vaccine.  


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 40 of 90 
CONFIDENTAL 
 
  
 
Following vaccination with live or attenuated component vaccines, the virus may be shed in 
bodily fluids, including stool, and there is a potential risk that the virus may be transmitted.  
General guidelines suggest that exposure should be avoided following vaccination with these 
vaccines for the stated time period: 
• Varicella or attenuated typhoid fever vaccination for 4 weeks following vaccination; 
• Oral polio vaccination for 6 weeks following vaccination; 
• Attenuated rotavirus vaccine for 10 days following vaccination; 
• Inhaled flu vaccine for 1 week following vaccination. 
5.6. 
Treatment Compliance 
The investigator or designee will be responsible for monitoring subject compliance through 
questioning the subject, reviewing the subject completed compliance record and documenting 
missed doses, if any, and visual inspection of the study medication bottles (used and unused).  
Study staff will counsel the subjects, as required to make sure subjects are compliant with study 
medication dosing. 
5.7. 
Randomization and Blinding 
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.   
Subjects will be assigned to 1 of the 4 treatment groups in a random manner and at a 1:1:1:1 
ratio. At Baseline (Visit 2), an investigational center staff member will assign study medication 
to eligible subjects by selecting an appropriate Subject Kit as detailed in the Pharmacy Manual.   
Blinding of study medication is important for validity of this study.  This study uses a double-
blind design.  The study medications are indistinguishable in appearance, as packaged and 
labeled. 
5.7.1. 
Unblinding the Study Medication 
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.   


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 41 of 90 
CONFIDENTAL 
 
  
 
 
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 3.4.1.2).  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. 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 42 of 90 
CONFIDENTAL 
 
  
 
6. 
STUDY MEDICATION MATERIALS AND MANAGEMENT 
6.1. 
Study Medication 
The study medications for this study are ATI-501 Oral Suspension in dosage strengths of 400 
mg, 600 mg, 800mg or Placebo Oral Suspension. The study medications are formulated as an 
oral suspension that are indistinguishable as packaged and labelled.  The inactive ingredients 
include: Povidone (Kollidon 30); Sodium Lauryl Sulfate (Kolliphor SLS); Sodium Phosphate, 
Dibasic, 7-Hydrate; Citric Acid, monohydrate; Hydrochloric Acid; Sodium Benzoate; and 
Purified Water.  
 
Table 4: 
Investigational Product 
STUDY MEDICATION INFORMATION 
Study medication name 
ATI-501 
ATI-501 
ATI-501 
Placebo 
Dosage Strength 
400 mg 
600 mg 
800 mg 
- 
Manufacturer 
Alliance Contract Pharma, Harleysville, PA 19438 
Pharmaceutical Form 
Oral Suspension 
Container 
30 mL amber plastic bottle  
Storage Conditions 
59°F to 77°F (15°C to 25°C) 
Dose regimen 
Route 
Oral 
Frequency 
Twice-daily 
Duration of administration 
24 weeks 
6.2. 
Packaging and Labeling 
The study medication must be used by the study subjects only.  The study medication will be 
supplied in single-dose bottles.  Investigational site staff will explain the administration of study 
medication to subjects.  Study medication will be provided by Aclaris Therapeutics, Inc. and 
labeled according to regulations as detailed in the Pharmacy Manual.   
6.3. 
Study Medication Storage 
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 kit at room temperature, away from heat, moisture, direct light, and to keep it 
from freezing and out of the reach of children. 
6.4. 
Study Medication Accountability and Disposal 
The Principal Investigator or designee is responsible for ensuring accountability for the 
investigational agent, including reconciliation of medications and maintenance of medication 
records.  Upon receipt of study medication, the clinical site will check for accurate delivery and 
acknowledge receipt by signing (or initialing) and dating the documentation provided.  A copy of 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 43 of 90 
CONFIDENTAL 
 
  
 
this document will be submitted to Aclaris Therapeutics, Inc. (or designee) by facsimile or e-mail 
(scanned copy) and the original 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 disposed of as detailed in the Pharmacy Manual. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 44 of 90 
CONFIDENTAL 
 
  
 
7. 
ASSESSMENT OF EFFICACY 
Note that all subject assessments should be performed in the order detailed in Table 5 prior to 
any investigator assessments.  The investigator may assist in determining the location of the 
target patch prior to subject assessments but should not review the subject’s assessments prior to 
completing the investigator assessments.  The investigator should perform the assessments in the 
order detailed in Table 6.  Detailed instructions for completing the subject and investigator 
assessments will be provided to the investigational center prior to the initiation of subject 
enrollment. 
7.1. 
Alopecia Target Scalp Patch Identification 
At Baseline (Visit 2), the investigator will ask the subjects with patchy AA (30% to 95% scalp 
hair loss), to identify the most bothersome patchy area of the scalp, which will be identified as 
the target patch.  Subjects must have an assessment of “no hair” or “a little hair” in the target 
scalp patch based on both the Clinician’s and Subject’s Alopecia Scalp Appearance Assessment 
(ASAA).  The target patch will be documented photographically at Baseline (Visit 2) and 
monthly throughout the study at the visits detailed in Schedule of Assessments (Table 3).    
In subjects with extensive hair loss, the target patch may be a large scalp surface area. In subjects 
with total scalp hair loss (AU or AT), this assessment should be completed as not applicable in 
both the source documentation and the eCRF.   
7.2. 
Subject Reported Outcome Assessments 
The subject will complete the assessments (questionnaires) in the order detailed in Table 5.  The 
subject must sign/initial and date the completed questionnaire to indicate he/she performed the 
assessment as instructed.  The staff member administering the questionnaires must document 
proper completion of the assessments in the subject’s source notes.


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 45 of 90 
CONFIDENTAL 
 
  
 
Table 5: Subject Assessments 
Order Subjects with Patchy AA  
(30% – 95%) Scalp Hair Loss 
Subjects with AU or AT (>95% hair loss) 
1. 
Alopecia Scalp Appearance Assessment 
for Patchy AA:  Subject Rating (ASAA-
AAP: SR) Appendix 3  
Alopecia Scalp Appearance Assessment for 
AT/AU:  Subject Rating (ASAA-AT/AU: SR) 
Appendix 10  
2. 
Alopecia Facial Hair Appearance Assessment:  Subject Rating (AFHA: SR) Appendix 4  
3. 
Subject Global Impression of Severity 
for Patchy AA (SGIS-AAP) Appendix 5 
Subject Global Impression of Severity for 
AT/AU (SGIS-AT/AU) Appendix 11  
4. 
Alopecia Impact Assessment (AIA) Appendix 6  
5. 
Subject Global Impression of Change (SGIC)* Appendix 14   
6. 
Subject Global Impression of Treatment 
Satisfaction for Patchy AA (SGITS-
AAP) Appendix 7  
Subject Global Impression of Treatment 
Satisfaction for AT/AU (SGITS-AT/AU) 
Appendix 12  
7. 
Subject Global Satisfaction with Hair 
Quality (SGSHQ) Appendix 8 
Subject Global Satisfaction with Hair Quality 
(SGSHQ) Appendix 13  
8. 
Dermatology Life Quality Index Appendix 9  
*Only assessed at final study treatment visit 
7.2.1. 
Alopecia Scalp Appearance Assessment (ASAA)  
Subjects with patchy AA (30 – 95% scalp hair loss) at Baseline (Visit 2), will assess appearance 
of hair loss in the target scalp patch and the whole scalp by completing Item 1 and 2 of the 
ASAA-AAP: SR at Baseline (Visit 2) and at the visits detailed in Schedule of Assessments 
(Table 3). At Baseline (Visit 2), the response for Item 1 of the ASAA-AAP: SR must be “no 
hair” or “a little hair” for the subject to be eligible for randomization.  The ASAA-AAP: SR is 
located in Appendix 3.   
Subjects with AU and AT (>95% scalp hair loss) at Baseline (Visit 2) will assess the appearance 
of the whole scalp using the ASAA-AT/AU: SR by the subject at the visits listed in the Schedule 
of Assessments (Table 3).  The ASAA-AT/AU: SR is located in Appendix 10.   
7.2.2. 
Alopecia Facial Hair Appearance Assessment (AFHA) for AA, AT and AU: 
Subject Rating (SR) (AFHA: SR) 
All subjects (AA, AT or AU) will complete the AFHA: SR.  An investigational staff member will 
instruct the subject to assess the facial hair areas (eyebrows, eyelashes and if male, beard), educate 
the subject on the AFHA: SR before each evaluation  at Baseline (Visit 2) and at the visits detailed 
in Schedule of Assessments (Table 3). The staff member should not influence the subject’s 
assessment. 
The AFHA: SR is in Appendix 4.   


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 46 of 90 
CONFIDENTAL 
 
  
 
7.2.3. 
Subject Global Impression of Severity (SGIS) 
The severity of the subject’s AA, AU or AT will be assessed by the all subjects at Baseline (Visit 
2) and at the visits detailed in Schedule of Assessments (Table 3) by the subject using the Global 
Impression of Severity Questionnaire in Appendix 5 for subjects with AA or Appendix 11 for 
subjects with AT/AU. 
7.2.4. 
Alopecia Impact Assessment (AIA):  Subject Rating 
The Investigator or study staff will instruct subjects with AA, AT or AU to answer the AIA 
(Appendix 6) during the study visit at Baseline (Visit 2), and the visits detailed in the Schedule 
of Assessments (Table 3).  
7.2.5. 
Subject Global Impression of Change (SGIC) 
The investigator or study staff will instruct subjects with AA, AU or AT to answer the SGIC 
questionnaire at their final study treatment 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 14. 
7.2.6. 
Subject Global Impression of Treatment Satisfaction (SGITS) 
The investigator or study staff will instruct subjects with AA, AU or AT to answer the SGITS 
questionnaire in relation to their satisfaction with the scalp hair regrowth.  Subjects will assess 
their satisfaction with the outcome of the study treatment on a 7-point satisfaction scale from 
“extremely satisfied” to “extremely dissatisfied” at the visits detailed in the Schedule of 
Assessments (Table 3).  Subjects with patchy AA (30%-95% scalp hair loss) will complete the 
SGITS-AAP found in Appendix 7.   Subjects with AT or AU (> 95% scalp hair loss) will 
complete the SGITS-AT/AU found in Appendix 12. 
7.2.7. 
Subject Global Satisfaction with Hair Quality (SGSHQ) 
The investigator or study staff will instruct the subject to answer the SGSHQ questionnaire in 
relation to their satisfaction with the quality of scalp hair right now.  Subjects will assess their 
satisfaction with the quality of their scalp hair on a 7-point satisfaction scale from extremely 
satisfied to extremely dissatisfied at the visits detailed in the Schedule of Assessments (Table 3).  
Subjects with patchy AA (30%-95% scalp hair loss) will complete the SGSHQ-AAP found in 
Appendix 8.   Subjects with AT or AU (> 95% scalp hair loss) will complete the SGSHQ-
AT/AU found in Appendix 13. 
7.2.8. 
Dermatology Life Quality Index (DLQI) 
The impact of AA, AU, or AT on the quality of life of subject will be assessed using the DLQI 
(Appendix 9) at the visits detailed in Schedule of Assessments (Table 3).  The investigator or 
study staff will instruct the subject to answer the questions based on the scalp hair loss instead of 
skin. 
7.3. 
Investigator Efficacy Assessments 
The investigator will complete the assessments detailed in Table 6 in the order listed.   


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 47 of 90 
CONFIDENTAL 
 
  
 
Table 6: 
Investigator Assessments 
Order 
Subjects with Patchy AA (30% – 95%) 
Scalp Hair Loss 
Subjects with AU or AT (>95% hair loss) 
1.  
Alopecia Scalp Appearance Assessment 
for Patchy AA:  Clinician Rating 
(ASAA-AAP: CR)  
Alopecia Scalp Appearance Assessment for 
AT/AU:  Clinician Rating (ASAA-AT/AU: 
CR) 
2.  
Alopecia Facial Hair Appearance Assessment:  Clinician Rating (AFHA: CR) 
3.  
Non-Scalp Hair Loss Assessment (NSHA) 
4.  
Physician Global Impression of Severity 
for Patchy AA (PhGIS-AAP) 
Physician Global Impression of Severity for 
AT/AU (PhGIS-AT/AU) 
5.  
Physician Global Impression of Change (PhGIC)* 
6.  
Hair Quality Assessment 
N/A 
7.  
SALT 
8.  
ALODEX 
9.  
Vellus and Indeterminate Hair Assessment 
*Only assessed at final study treatment visit 
 
7.3.1. 
Alopecia Scalp Appearance Assessment (ASAA) Clinician Rating (CR) 
The investigator will complete the ASAA-AAP: CR for subjects with patchy AA (30%-95% 
scalp hair loss) or the ASAA-AT/AU: CR for subjects with AT or AU (>95% scalp hair loss) at 
the visits listed in Table 3, Schedule of Assessments.  
For subjects with patchy AA (30% to 95% scalp hair loss), the appearance of the target scalp 
patch and the whole scalp will be assessed by the Investigator by completing Items 1 and 2 of the 
ASAA-AAP:CR (Section 7.3.1.1).   
For subjects with AT or AU (scalp hair loss > 95%), the appearance of the whole scalp will be 
assessed by the investigator by completing Item 1 of the ASAA-AT/AU: CR (Section 7.3.1.2).  
At Baseline (Visit 2), the score for ASAA-AAP: CR Item 1 for subjects with patchy AA (30% to 
95% scalp hair loss) must be “no hair” or “a little hair” for the subject to be eligible for 
randomization. 
   
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 48 of 90 
CONFIDENTAL 
 
  
 
7.3.1.1. 
Alopecia Scalp Appearance Assessment (ASAA) for Patchy AA: Clinician 
Rating (CR) (ASAA-AAP: 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 
 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 
 
7.3.1.2. 
Alopecia Scalp Appearance Assessment (ASAA) for AT and AU: Clinician 
Rating (CR) (ASAA-AT/AU: CR) 
 
Instructions: 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 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 49 of 90 
CONFIDENTAL 
 
  
 
7.3.2. 
Alopecia Facial Hair Appearance Assessment (AFHA) for AA, AT and AU: 
Clinician Rating (CR) (AFHA: CR) 
For subjects with AA, AU or AT, the appearance of the subject’s facial hair (eyebrows, 
eyelashes and if male, beard) will be assessed using the AFHA: CR by the investigator at 
Baseline (Visit 2) and the visits listed in the Schedule of Assessments (Table 3).   
The AFHA: CR is the investigator’s assessment of the subject’s facial hair (eyebrow(s), eyelashes, 
and if male, beard) at a particular point in time. The investigator should NOT refer to any other 
assessments to assist with these assessments. The investigator or designee will assess the affected 
facial hair areas (eyebrows, eyelashes and if male, beard) using the scales below and report the one 
response that best describes the amount of eyebrow, eyelash and if applicable beard hair present.  
Right and left eyebrow and eyelashes should be evaluated separately.  The AFHA is a tool to assess 
the presence of hair in expected areas of growth.  As such, unexpected hair growth (e.g. facial/beard 
hair in women) should be documented as an adverse event rather than on the AFHA. 
 
Instructions for item 1a: Please mark an “X” in the box (☐) that best describes the appearance 
of the subject’s left eyebrow hair right now. Please select the one response that best represents 
your answer. 
 
 Full eyebrow hair 
 Most eyebrow hair 
 Some eyebrow hair 
 A little eyebrow hair 
 No eyebrow hair 
 
Instructions for item 1b: Please mark an “X” in the box (☐) that best describes the appearance 
of the subject’s right eyebrow hair right now. Please select the one response that best represents 
your answer. 
 
 Full eyebrow hair 
 Most eyebrow hair 
 Some eyebrow hair 
 A little eyebrow hair 
 No eyebrow hair 
 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 50 of 90 
CONFIDENTAL 
 
  
 
Instructions for item 2a: Please mark an “X” in the box (☐) that best describes the appearance 
of the subject’s left eyelashes right now. Please select the one response that best represents your 
answer. 
 
 Full eyelashes 
 Most eyelashes 
 Some eyelashes 
 A little eyelashes 
 No eyelashes 
 
Instructions for item 2b: Please mark an “X” in the box (☐) that best describes the appearance 
of the subject’s right eyelashes right now.  Please select the one response that best represents 
your answer. 
 
 Full eyelashes 
 Most eyelashes 
 Some eyelashes 
 A little eyelashes 
 No eyelashes 
 
Instructions for item 3: Please mark an “X” in the box (☐) that best describes the appearance 
of the subject’s beard hair right now. Beard hair can include hair on the chin, cheeks, neck, and 
above the upper lip. Please select the one response that best represents your answer. 
 
 Full beard hair 
 Most beard hair 
 Some beard hair 
 A little beard hair 
 No beard hair 
 
 
 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 51 of 90 
CONFIDENTAL 
 
  
 
7.3.3. 
Non-Scalp Hair Loss Assessment (NSHA) 
The investigator will assess body hair (axillary, truncal, genital, extremities) and facial hair 
including nasal hair using a 3-point scale; no hair loss, some hair loss and total hair loss.  Nasal 
hair will be assessed by presence or absence only. These assessments will be completed at 
Baseline (Visit 2) and the visits listed in the Schedule of Assessments (Table 3) (Olsen, 2011).   
 
Instructions: Please mark an “X” in the box (☐) that best describes the appearance of the 
subject’s body hair loss right now. Please select the one response that best represents your 
answer. 
 
 
Mark “X” 
Body Hair Loss (axillary, truncal, genital, extremities) 
 
B0 
No body hair loss 
 
B1 
Some hair loss 
 
B2 
Total body hair loss 
 
 
Instructions: Please mark an “X” in the box (☐) that best describes the appearance of the 
subject’s nasal hair loss right now. Please select the one response that best represents your 
answer. 
 
Mark “X” 
Nasal Hair Loss 
 
NH0 
No nasal hair loss 
 
NH1 
Some to total nasal hair loss 
 
7.3.4. 
PHYSICIAN GLOBAL IMPRESSION OF SEVERITY (PhGIS) 
The severity of the subject’s AA, AU or AT will be assessed at Baseline and at the visits detailed 
in Schedule of Assessments (Table 3), by the investigator using either the PhGIS-AAP for 
subjects with patchy AA (30% - 95% scalp hair loss) (Section 7.3.4.1) or the PhGIS-AT/AU for 
subjects with AT or AU (> 95% scalp hair loss) (Section 7.3.4.2). 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 52 of 90 
CONFIDENTAL 
 
  
 
7.3.4.1. 
PHYSICIAN GLOBAL IMPRESSION OF SEVERITY (PhGIS-AAP) 
Please mark an “X” in the box (
) that best describes the severity of the subject’s patchy 
alopecia areata right now. 
Overall, how severe is the subject’s patchy alopecia areata right now? 
☐ Mild 
☐ Moderate 
☐ Severe 
☐ Very Severe 
☐ Extremely Severe 
7.3.4.2. 
PHYSICIAN GLOBAL IMPRESSION OF SEVERITY (PhGIS-AT/AU) 
Please mark an “X” in the box (
) that best describes the severity of the subject’s alopecia 
totalis or alopecia universalis right now. 
Overall, how severe is the subject’s alopecia totalis or alopecia universalis right now? 
☐ Mild 
☐ Moderate 
☐ Severe 
☐ Very Severe 
☐ Extremely Severe 
7.3.5. 
Physician Global Impression of Change (PhGIC) 
The investigator will assess the global impression of change in the subject’s hair loss (AA, AT or 
AU) at Week 24 (Visit 9) using the 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;  
  
7=Very much worse since the initiation of treatment. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 53 of 90 
CONFIDENTAL 
 
  
 
7.3.6. 
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 and then monthly during the study.  For subjects with AU or 
AT, the hair pull test will not be conducted. 
7.3.6.1. 
Hair Pull Test 
The hair pull test is performed at the edge of the alopecic (target) 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) (exclamation point hair) 
7.3.7. 
Severity Alopecia Tool (SALT) Score 
The SALT score is a measurement of the amount of terminal scalp hair loss. The investigator 
will assess the SALT score using an iPad provided by Aclaris at screening, Baseline, Day 15 
(Visit 3) and at the visits detailed in Schedule of Assessments (Table 3).  The SALT score must 
be determined prior to the ALODEX score.  At Baseline (Visit 2), the SALT score must be 
determined prior to randomization and the score must be within 30% to 100% total scalp hair 
loss for the subject to receive study treatment.  Equipment, supplies, training and the detailed 
Reference Guide will be provided to the investigational site prior to the initiation of subject 
enrollment. 
7.3.8. 
Alopecia Density and Extent Score (ALODEX) 
The ALODEX score is a measurement of the amount of terminal scalp hair loss.  The 
investigator will calculate the ALODEX score using the iPad provided by Aclaris at Screening, 
Baseline, Day 15 (Visit 3), and at the visits detailed in Schedule of Assessments (Table 3).  The 
ALODEX score must be determined after the SALT score.  At Baseline (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. 
7.3.9. 
Vellus and Indeterminate Hair Assessment 
The investigator will assess if vellus and indeterminate hair are present on the scalp by 
completing the question: 
Is vellus hair present in the areas of hair loss? Y, N 
Is indeterminate hair present in the areas of hair loss?  Y, N 
Hair types are characterized by the diameter and length of the hair shafts.  Vellus hair is soft, 
hypopigmented, unmedullated and less than 0.03 mm in diameter and less than 1 cm in length.  


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 54 of 90 
CONFIDENTAL 
 
  
 
Terminal hair is longer, coarser, often medullated, pigmented, and > 0.06 mm in diameter and > 
1 cm in length.  Indeterminate hairs are intermediate in size between terminal and vellus hairs 
(>0.03 mm and <0.06 mm in diameter).   
7.4. 
Photographic Assessment 
A qualified investigational staff member will take standardized photographs of the scalp at 
Baseline and then monthly during the study.  The photographs are to document the Baseline hair 
loss and hair growth during treatment.  Photography is a required element of the study 
procedures and is not considered optional.  During initial study discussion as part of consent 
procedures, site staff should ensure that subjects are fully aware of this aspect of study 
participation.  
Subjects should be instructed to maintain the same hairstyle and color throughout the study.  It is 
important for the staff member to clip the hair as detailed in the instructions provided, so the 
areas of hair loss and possible regrowth are visible at baseline and monthly throughout the study.  
Equipment, supplies, training and detailed instructions for obtaining and managing photographs 
and clipping the hair will be provided to the investigational center prior to the initiation of 
subject enrollment. 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 55 of 90 
CONFIDENTAL 
 
  
 
8. 
ASSESSMENT OF SAFETY 
8.1. 
Safety Parameters 
Safety will be assessed throughout the study by the investigator or a designated and appropriately 
trained staff member. 
8.1.1. 
Demographic/Medical History/ 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 
alopecia history at screening (Appendix 1).  The subject’s alopecia history is captured on a 
separate source document and eCRF and is not documented as part of the subject’s general 
medical history. 
8.1.2. 
Vital Signs 
Vital signs will be measured at each visit during the study. The following items will be 
measured: 
• Body temperature 
• Pulse rate 
• Respiration rate 
• Blood pressure (systolic and diastolic) after the subject sits quietly for at least 5 
minutes 
• Height (at Visit 1 only) 
• Weight (at Visit 1 only) 
Any measure that is, in the opinion of the investigator, abnormal AND clinically significant (CS) 
must be recorded as medical history if found prior to the first study medication administration, or 
as an AE if found after the first dose of study medication.  
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.  
8.1.3. 
Physical Examination 
The investigator or designee will perform a physical examination for all body systems at 
Screening (Visit 1) and end of treatment Week 24 (Visit 9).  The skin assessment portion of the 
Physical Examination does not require documentation of alopecia as an abnormality since it is 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 56 of 90 
CONFIDENTAL 
 
  
 
the indication of interest for this study and required for participation.  In the absence of any other 
abnormalities, skin should be considered “Normal” for these subjects. 
8.1.4. 
Electrocardiogram (ECG) 
Standard 12-lead ECGs will be performed by a qualified staff member at Screening (Visit 1), 
Visit 3, and Visit 9 as detailed in Schedule of Assessments (Table 3).  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.  
A central lab, eResearchTechnology, 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 on a separate report which includes a copy of the tracing.   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 medical history if found prior to the start of the first dose of study medication or as 
an AE if found after the start of the first dose of study medication (see Section 8.2 ). 
8.1.5. 
Clinical Laboratory Assessments 
A qualified staff member will collect non-fasting samples for clinical laboratory analysis at the 
visits detailed in Schedule of Assessments (Table 3).  Samples will be sent to a central laboratory 
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 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 57 of 90 
CONFIDENTAL 
 
  
 
Phosphorus 
    Monocytes 
Potassium 
    Neutrophils 
Sodium 
 
Total bilirubin 
Urinalysis 
Total protein 
 
Uric acid 
 
Total cholesterol, LDL, HDL, 
Triglycerides  
 
Urine Pregnancy Test for WOCBP 
(Screening, Baseline, at the visits 
detailed in Schedule of Assessments 
(Table 3). 
 
 
Screening Only 
Virology (HepB, HCV, HIV) 
Quantiferon Gold 
Total Iron Binding Capacity 
(TIBC) 
Serum iron 
Serum Ferritin 
T3/ Free T4, TSH 
Serum pregnancy 
The following clinical laboratory tests:  TIBC, serum iron, serum ferritin, T3/ Free T4, TSH are 
drawn at screening to rule out any underlying conditions that could be causing alopecia. Total 
cholesterol, LDL, HDL and Triglycerides will be assessed at all visits. The results of the clinical 
laboratory tests will be reported on the central 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 and the Study Medication Interruption Criteria Table 2 for each 
subject prior to Baseline (Visit 2). Subjects with Screening laboratory values meeting the Study 
Medication Interruption Criterial found in Table 2 must have repeat laboratory testing performed 
with results meeting the minimum criteria for resumption in order to initiate treatment at 
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. The investigator must review all laboratory reports in a timely manner. 
8.1.6. 
Pregnancy Testing 
Subjects who are WOCBP should have a UPT performed early in the screening procedures 
(following informed consent) which shows negative results in order to avoid the continuation of 
what would then be unnecessary screening testing.  Subjects who are WOCBP must also have a 
negative serum pregnancy test result from 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 the visits detailed 
in Schedule of Assessments (Table 3). The UPT kits provided by the Central lab have a 
minimum sensitivity of 25-mIU ß-HCG/milliliter (mL) of urine. If the result of any post-


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 58 of 90 
CONFIDENTAL 
 
  
 
treatment urine pregnancy test is positive, the subject will be withdrawn from the study and the 
subject’s pregnancy documented and followed. 
8.1.7. 
Pharmacokinetic Assessments 
At selected sites, a qualified staff member will collect a 4.5 mL sodium citrate vacutainer for 
analysis of ATI-502 predose at Visit 2 and at Visits 4, 6, and 9, 12 hours (± 30 minutes) after the 
prior evening dose.  Samples will be sent to a bioanalytical laboratory for analysis.  Refer to the 
pharmacokinetic laboratory manual for handling and shipping instructions.  
8.2. 
Adverse and Serious Adverse Events 
Adverse events will be monitored throughout the study and reported on the appropriate Aclaris 
Therapeutics, Inc. AE eCRF. 
8.2.1. 
Definition of Adverse Events 
8.2.1.1. 
Adverse Event (AE) 
An AE is the development of an undesirable medical condition or the deterioration of a pre-
existing medical condition following or during exposure to a pharmaceutical product, whether or 
not considered casually related to the product.   
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. 
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.  Hair growth in unexpected areas, such as 
facial hair in women, should be reported as an adverse event. 
Any CS abnormality discovered prior to the first study medication treatment should be reported 
as medical history, not as an AE. 
All AEs that occur after any subject has been enrolled, before treatment, during treatment, or 
within 30 days following the cessation of treatment, whether or not they are related to the study, 
must be recorded in the subject’s source documents and in the Aclaris’ electronic case report 
form (eCRF).  Changes to a subject’s medical condition that occur between signing an ICF and 
beginning treatment should be captured in the medical history. 
8.2.1.2. 
Serious Adverse Event (SAE) 
A serious adverse event is an AE occurring during any study phase (i.e., Baseline, Treatment, 
Washout, or Follow-up), and at any dose of the investigational product, comparator or placebo, 
that fulfills one or more of the following: 
• Results in death 
• It is immediately life-threatening 
• It requires in-patient hospitalization or prolongation of existing hospitalization 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 59 of 90 
CONFIDENTAL 
 
  
 
• It results in persistent or significant disability or incapacity 
• Results in a congenital abnormality or birth defect 
• It is an important medical event that may jeopardize the patient or may require medical 
intervention to prevent one of the outcomes listed above. 
The term “life threatening” refers to an event in which the subject was at risk of death at the time 
of event; it does not refer to an event that hypothetically might have caused death if it were more 
severe. 
 
Important medical events are those that may not be immediately life threatening, result in death 
or hospitalization, but are clearly of major clinical significance and may jeopardize the subject or 
require intervention to prevent one of the outcomes listed in the SAE definition above. These 
should also usually be considered serious. 
All SAEs that occur from the time of informed consent until 30 days following the cessation of 
study medication dosing, whether or not they are related to the study, must be recorded on the 
SAE forms provided by Aclaris Therapeutics, Inc. 
8.2.1.3. 
Unexpected adverse event 
An AE is considered unexpected if it is not listed in the Investigator’s Brochure or is not listed at 
the specificity or severity that has been observed. 
8.3. 
Reporting Adverse Events 
8.3.1. 
Adverse event reporting period 
The investigator must start reporting non-serious AEs from the time of the subject’s first dose of 
study medication until 30 days after the last dose of study medication. Reporting for SAEs must 
start when the subject signs the ICF and continue until 30 days past the subject’s last dose of 
study medication, whether or not they are related to the study. 
8.3.2. 
Severity 
The investigator is to define the severity of each AE using the following definitions as a 
guideline. The investigator will consider the range of the possible severity of the event and 
identify the severity that is the most appropriate according to her/his medical judgment. 
 
Mild – Awareness of signs or symptom, but easily tolerated 
Moderate – Discomfort, enough to cause interference with usual activity 
Severe – Incapacitating with inability to perform usual activity 
8.3.3. 
Relationship to study medication 
The investigator will determine if there is a reasonable causal relationship between the study 
medication and an AE or not. The investigator will use her/his best medical judgment and 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 60 of 90 
CONFIDENTAL 
 
  
 
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). 
8.3.4. 
Procedures for reporting adverse events 
At each post-enrollment visit, the investigator will question the subject to elicit AEs using a non-
directive question such as “Has there been any change in your health since the previous study 
visit?”  If appropriate, based on the subject’s response to non-directed questioning to elicit AEs, 
the investigator will follow-up with directed questions and appropriate evaluations.  
Any AE noted during the reporting period must be reported in the source documents and on the 
appropriate AE eCRF. AEs that are defined as “Not Related” to the study medications will be 
followed until they are resolved or until the subject’s last study visit. AEs that are defined as 
“Related” to the study medications will be followed until they are resolved or, if not resolved 
after the subject’s last study visit, until in the opinion of the investigator, the AE reaches a 
clinically stable outcome with or without sequelae. 
8.3.5. 
Procedure for reporting a serious adverse event 
Upon becoming aware of a SAE occurring during the AE reporting period, whether or not related 
to the study medications, the investigator must: 
1. Take the appropriate medical action to ensure the subject’s safety. 
2. Immediately inform the Safety Monitor of the SAE by email, ensuring that the subject 
information is deidentified (only subject initials and subject number) to: ProPharma, 
Email: clinicalsafety@propharmagroup.com. 
3. Print a copy of the email confirmation from ProPharma and place in the study file. 
4. Within 24-hours complete, as fully as possible, an AE eCRF and an SAE form; e-mail the 
forms and any other relevant information (e.g., concomitant medication eCRF, medical 
history eCRF, laboratory test results) to ProPharma (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 SAE 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. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 61 of 90 
CONFIDENTAL 
 
  
 
6. Inform the Aclaris Therapeutics, Inc. Safety Monitor of SAE updates, via telephone, 
followed by an SAE form update sent by e-mail. 
7. Comply with the appropriate regulatory requirements and Aclaris Therapeutics, Inc. 
instructions regarding reporting of the SAE to the responsible Institutional Review Board 
(IRB) or Ethics Committee (EC). 
8.4. 
PREGNANCY 
8.4.1. 
Definition of Women of Child Bearing Potential (WOCBP) 
WOCBP includes any female who has experienced menarche and who has not undergone 
successful surgical sterilization (e.g., hysterectomy, bilateral tubal ligation, or bilateral 
oophorectomy) or is not postmenopausal. Postmenopausal is defined as ≥12 months with no 
menses without an alternative medical cause.  WOCBP must have a negative serum pregnancy 
test at screening and a negative UPT at Baseline prior to randomization. 
8.4.2. 
Highly Effective Methods of Birth Control 
The Investigator or subinvestigator will discuss the potential risk factors associated with 
pregnancy and the importance of maintaining a highly effective method of contraception 
throughout the study with all WOCBP (for example, those which result in a low failure rate - i.e., 
less than 1% per year- when used consistently and correctly).  All WOCBP must use a highly 
effective method of birth control during the study and for 30 days after the final dose of study 
medication in a manner such that risk of failure is minimized.   
 
Highly effective methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 
o implantable 
• intrauterine device (IUD) 
• intrauterine hormone-releasing system (IUS) 
• vasectomized partner1 
• sexual abstinence2 
1Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner 
of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the 
surgical success.  
2 Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study treatments. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual 
lifestyle of the subject. 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 62 of 90 
CONFIDENTAL 
 
  
 
WOCBP must be on a highly effective method of birth control for the following timeframes prior 
to study entry:  
• Implants (on a stable dose for ≥30 days) 
• Injectables (on a stable dose for ≥30 days) 
• Patches (on a stable dose for ≥30 days) 
• Combined oral contraceptives (on a stable dose for ≥30 days) 
• Intrauterine devices (inserted for ≥30 days). 
Prior to trial enrollment, WOCBP must be advised of the importance of avoiding pregnancy 
during trial participation and of the potential risk factors associated with pregnancy while in the 
study.  The subject must sign an informed consent form documenting this discussion.  During the 
trial, all WOCBP will be instructed to contact the investigator immediately if they suspect they 
might be pregnant (e.g., missed or late menstrual period). 
If a subject or investigator suspects that the subject may be pregnant prior to study medication 
administration, the study medication must be withheld until the results of a pregnancy test are 
available.  If pregnancy is confirmed, the subject must not receive study medication and must be 
discharged from the study.  
If, following study medication administration, it is determined that the subject or partner of a 
male subject may have been or was pregnant at the time of study medication exposure (including 
30 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. 
  
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 63 of 90 
CONFIDENTAL 
 
  
 
9. 
STATISTICS 
9.1. 
Sample Size and Power Calculations 
The planned sample size is 95 enrolled subjects with approximately 45 subjects enrolled with AT 
or AU.   
The sample size estimate was based on published results from a similar study (Crispin et al.  
2016) where 32% of subjects receiving active drug achieved at least a 50% reduction in hair loss 
(SALT50) under similar conditions.  For the current study, the primary efficacy analysis is mean 
percent change in hair loss, evaluated using SALT scores.  That analysis is expected to have 
greater statistical sensitivity than the SALT50 responder analysis, which is also a secondary 
efficacy analysis in the current study.   
We assume the pooled results of 600mg and 800mg treatment groups in the current study will 
achieve the same or higher SALT50 response rate (32%) as the published results above, and 
pooled Vehicle plus 400mg treatment groups will not achieve more than a 6% SALT50 response 
rate.  Based on a comparison of those two pooled groups, the current study is anticipated to have 
no less than 80% power with a 10% subject dropout rate for the SALT50 analysis.  Because the 
primary efficacy analysis of mean percent change in hair loss using SALT scores is expected to 
be more sensitive than the SALT50 responder analysis, the power for the primary analysis is also 
expected to be no less than 80%.  
9.2. 
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 received at least 1 dose 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: 
• Inclusion or Exclusion criteria not met 
• Concomitant medications taken during the study that interfere with efficacy 
• Did not administer at least 75% of study medication  
• Did not complete Week 24 (Visit 9). 
9.3. 
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. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 64 of 90 
CONFIDENTAL 
 
  
 
9.4. 
Efficacy Analyses 
Hair regrowth is determined based on both percent change from baseline (Baseline SALT – 
Follow-up SALT/Baseline SALT) and absolute change from baseline (Baseline SALT – Follow-
up SALT).   
9.4.1. 
Primary Efficacy Analyses 
The primary efficacy variable will be the percent change from Baseline (Visit 2) in the SALT 
score at Visit 9 (Week 24).  Missing data for the primary endpoint will be imputed using Last 
Observation Carried Forward (LOCF) methodology.  The analysis will be conducted on the 
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 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. 
 
9.4.2. 
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 change from Baseline in the ALODEX score, 
ASAA (CR & SR), AFHA (CR & SR), PhGIS, SGIS, SGSHQ, AIA, and DLQI as well as the 
proportion of subjects achieving a ≥ 50% hair growth compared with Baseline based upon the 
SALT score and ALODEX score, separately.  SGITS responses at Week 12, 24, and 28 will be 
summarized.  Various secondary responder efficacy endpoints will be defined based upon the 
SALT score, the ALODEX score 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 9) will be used in the 
psychometric evaluation of the scores from the ASAA (CR and SR), respectively.  Non-Scalp 
Hair Loss Assessment, Vellus and Indeterminate Hair Assessment and Hair Quality Assessment 
including normalization of exclamation point hairs and hair shedding will be described.  The 
analysis for the percent change in ALODEX score will use the same methodology as specified 
for the primary efficacy analysis.  Other parameters will be analyzed as detailed in the SAP. 
 
9.5. 
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 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 65 of 90 
CONFIDENTAL 
 
  
 
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-dose values in vital signs. Adverse 
event summaries will be presented by study medication showing the proportion of subjects 
experiencing adverse events, both overall and by MedDRA System Organ Class. 
 
9.6. 
Pharmacokinetic Analyses 
The concentration of ATI-502 in the blood will be summarized (mean [SD], minimum, median 
maximum) pre-dose (Visit 2) and approximately 12-hr post dosing at Visits 4, 6 and 9.   
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 66 of 90 
CONFIDENTAL 
 
  
 
10. 
TRAINING, DATA HANDLING AND RECORD KEEPING 
10.1. 
Training 
For each investigational center, there will be an initiation visit prior to enrolling any study 
subjects.  It is strongly recommended that all investigators, other evaluators, study nurses, study 
coordinators or other applicable personnel attend this visit.  During this visit, participants will be 
trained to the protocol, study specific procedures, and the 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. 
10.2. 
Data Collection 
The Investigator must maintain required records for all study subjects.  Data for this study will 
be recorded in the subject's source document and on the eCRFs.  All data on these eCRFs should 
be recorded completely and promptly.  A copy of the completed eCRFs for each subject will be 
retained by the investigational center. 
Records of the subject’s participation in this study will be held confidential except as disclosure 
is required by law. The study doctor, the sponsor, persons working on behalf of the sponsor, and 
under certain circumstances, the United States Food and Drug Administration and the 
Institutional Review Board will be able to inspect and copy confidential study-related records 
that identify subjects by name. Therefore, absolute subject confidentiality cannot be guaranteed. 
If the results of this study are published or presented at meetings, the subject’s identity will not 
be revealed. 
10.3. 
Data Management 
Data-management activities of this study will be subcontracted.  Edit checks and review 
processes will be performed by the sub-contractor until all data clarifications are resolved. The 
data will be exported to be stored in SAS datasets (or equivalent) by the sub-contractor. After all 
data clarifications are resolved and subject’s evaluability is determined, the database will be 
locked. 
10.4. 
Study Monitoring 
Before an investigational site can enter a patient into the study, a representative of Aclaris 
Therapeutics, Inc. will visit the investigational study site to: 
• Determine the adequacy of the facilities 
• Discuss with the investigator(s) and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of Aclaris Therapeutics, Inc. or its 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 67 of 90 
CONFIDENTAL 
 
  
 
representatives.  This will be documented in a Clinical Study Agreement between Aclaris 
Therapeutics, Inc. and the investigator. 
During the study, a monitor from Aclaris Therapeutics, Inc. or representative will have regular 
contacts with the investigational site, for the following: 
• Provide information and support to the investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the case report forms, and that investigational product 
accountability checks are being performed 
• Perform source data verification.  This includes a comparison of the data in the case 
report forms with the patient’s medical records at the hospital or practice, and other 
records relevant to the study.  This will require direct access to all original records for 
each patient (e.g. clinic charts). 
• Record and report any protocol deviations not previously sent to Aclaris Therapeutics, 
Inc. 
• Confirm AEs and SAEs have been properly documented on CRFs and confirm any SAEs 
have been forwarded to Aclaris Therapeutics, Inc. and those SAEs that met criteria for 
reporting have been forwarded to the IRB. 
The monitor will be available between visits if the investigator(s) or other staff needs 
information or advice. 
10.5. 
Source Documentation 
Investigators must keep accurate separate records (other than the eCRFs) of all subjects' visits 
that include all pertinent study related information.  A statement should be made indicating that 
the subjects have been enrolled in this clinical study and have provided written informed 
consent.  Any AEs must be completely documented. Source documentation includes results of 
any diagnostic tests conducted during the study.   
10.6. 
Inspection of Records 
Aclaris or designee will be allowed to conduct site visits to the investigation facilities for the 
purpose of monitoring any aspect of the study. The Investigator agrees to allow the monitor to 
inspect the drug storage area, study medication stocks, drug accountability records, subject charts 
and study source documents, and other records relative to study conduct. 
10.7. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 2 
years after the last marketing application approval, or if not approved 2 years following the 
discontinuance of the test article for investigation. If it becomes necessary for Aclaris or the 
Regulatory Authority to review any documentation relating to the study, the Investigator must 
permit access to such records. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 68 of 90 
CONFIDENTAL 
 
  
 
11. 
QUALITY CONTROL AND QUALITY ASSURANCE 
The study is conducted under the sponsorship of Aclaris Therapeutics, Inc. in compliance with 
the applicable regulatory requirements as well as applicable ICH guidelines, Declaration of 
Helsinki, and in respect of the Aclaris Therapeutics, Inc. and/or sub-contractor SOPs for study 
conduct and monitoring. 
Audits may be carried out by Aclaris Therapeutics, Inc. or Aclaris Therapeutics, Inc.’s 
representatives, and inspections may be performed by regulatory authorities or IRB/ECs before, 
during or after the study.  The investigator will provide the auditing/inspecting group direct 
access to all study records (e.g., eCRFs, subject medical records, study medication dispensing 
records) and the investigational center study facilities. The investigator and study staff will be 
available and will assist the auditing/inspecting groups as appropriate. 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 69 of 90 
CONFIDENTAL 
 
  
 
12. 
ETHICS 
12.1. 
Ethics Review 
This protocol, informed consent form, any information provided to subjects, subject-recruiting 
advertisements, and any amendments to these items will receive IRB/EC approval prior to use. 
The IRB/EC must receive a copy of the Investigator’s Brochure, all protocol amendments, safety 
reports and other study related information as required by regulation or the IRB/EC procedures. 
12.2. 
Ethical Conduct of the Study 
The rights, safety and well-being of the subjects are the most important considerations in this 
study and take priority over the interests of society and science.  
This study will be conducted in accordance with the ethical principles originating from the 
Declaration of Helsinki, the current 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. 
12.3. 
Written Informed Consent 
The Principal Investigator(s) at each center will ensure that the subject is given full and adequate 
oral and written information about the nature, purpose, possible risk and benefit of the study.  
Subjects must also be notified that they are free to discontinue from the study at any time.  The 
subject should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The subject’s signed and dated informed consent must be obtained before conducting any study 
procedures.  The Principal Investigator(s) must maintain the original, signed Informed Consent 
Form.  A copy of the signed Informed Consent Form must be given to the subject. 
12.4. 
Study Conduct and Protocol Amendments 
With the exception of eliminating an immediate hazard to a subject, the investigator should not 
deviate from the protocol or implement any changes without prior written approval from the 
Aclaris Therapeutics, Inc.’s representative or designee and prior review and documented 
approval from the IRB/EC. 
 
Changes that involve only logistical or administrative changes are allowed.  The investigator 
should document and explain any deviation from the protocol.  A protocol deviation is a non-
adherence to protocol-specific study procedures or schedules that does not increase the risk to a 
study subject and does not affect the scientific integrity of the study.   
 
A protocol violation is defined as any divergence from the protocol-specific study procedures or 
schedules that may 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. 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 70 of 90 
CONFIDENTAL 
 
  
 
12.5. 
Regulatory Documents 
The investigator must maintain a study file containing current and complete regulatory 
documentation in compliance with the current ICH E6 GCP guideline. This file will be reviewed 
as part of the routine monitoring for this study. 
 
12.6. 
Contractual Requirements 
A contractual agreement will be signed between Aclaris Therapeutics, Inc. and each investigator.  
This document will contain supplemental information, including financial terms, confidentiality, 
study schedule, third party responsibility, and publication rights. 
 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 71 of 90 
CONFIDENTAL 
 
  
 
13. 
LIST OF REFERENCES 
Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: Part II. 
Treatment. J Am Acad Dermatol. 2010;62(2):191-202. 
Arca E, Muşabak U, Akar A, Erbil AH, Taştan HB. Interferon-gamma in alopecia 
areata. Eur J Dermatol. 2004 Jan-Feb;14(1):33-6.  
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.  
Crispin MK et al. Safety and efficacy of the JAK inhibitor tofacitinib cirate in patients with alopecia 
areata.  JCI Insight. 2016;1(15):1-15. 
Delamere FM, Sladden MJ, Dobbins HM, Leonardi-Bee J. Interventions for alopecia areata. 
Cochrane Database Syst Rev. 2008;16(2). 
Gilhar A, Kam Y, Assy B, Kalish RS. Alopecia areata induced in C3H/HeJ mice by 
interferon-gamma: evidence for loss of immune privilege. J Invest Dermatol. 2005;124(1):288-9.  
Gupta AK. Efficacy of tofacitinib in treatment of alopecia universalis in two patients. J Eur Acad 
Dermatol Venereol. 2016;30(8):1373-1378. 
Hirota R, Tajima S, Yoneda Y, Okada M, Tashiro J, Ueda K, Kubota T, Yoshida R. 
Induction of hair regrowth in the alopecia site of IFN-gamma knockout mice by 
allografting and IFN-gamma injection into the transplantation site. J Interferon  
Cytokine Res. 2003 Aug;23(8):433-9. 
Hordinsky MK. Current Treatments for Alopecia Areata. J Investig Dermatol Symp Proc. 
2015;17(2):44-46. 
Jabbari A, Dai Z, Xing L, et al. Reversal of Alopecia Areata Following Treatment With the JAK1/2 
Inhibitor Baricitinib. EBioMedicine. 2015;2(4):351-355. 
Jabbari A, Cerise JE, Chen JC, Mackay-Wiggan J, Duvic M, Price V, Hordinsky M, Norris D, 
Clynes R, Christiano AM. Molecular signatures define alopecia areata 
subtypes and transcriptional biomarkers. EBioMedicine. 2016 May;7:240-7. 
Kim BY and Kim HS. Successful hair growth in a Korean patient with alopecia universalis 
following tofacitinib treatment. Singapore Med. J., 2017 May; 58(5): 279-280. 
Kuwano Y, Fujimoto M, Watanabe R, Ishiura N, Nakashima H, Ohno Y, Yano S, 
Yazawa N, Okochi H, Tamaki K. Serum chemokine profiles in patients with alopecia  
areata. Br J Dermatol. 2007:157(3):466-73.  
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.  


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 72 of 90 
CONFIDENTAL 
 
  
 
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. 
Pieri L, Guglielmelli P, Vannucchi AM. Ruxolitinib-induced reversal of alopecia universalis in a 
patient with essential thrombocythemia. Am J Hematol. 2015;90(1):82-83. 
Price VH. Treatment of Hair Loss. N Eng J Med. 1999;341(13):964-973. 
Price VH, Hordinsky MK, Olsen EA, et al. Subcutaneous efalizumab is not effective in the 
treatment of alopecia areata. J Am Acad Dermatol. 2008;58(3):395-402. 
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. 
 
 
 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 73 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 1. ALOPECIA AREATA HISTORY 
The following AA history will be obtained: 
 
1. Onset date of alopecia 
 
2. Onset date of current episode of AA, AU or AT 
 
3. Does the subject have AA, AU or AT? 
 
4. Does the subject have an ophiasis pattern of hair loss? 
a. Ophiasis only 
b. Ophiasis and AA 
 
5. Did the subject use previous therapies for AA, AU or AT? 
 
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-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 74 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 2. 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-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 75 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 3. ALOPECIA SCALP APPEARANCE ASSESSMENT FOR 
PATCHY AA: SUBJECT RATING (ASAA-AAP: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-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 76 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 4. ALOPECIA FACIAL HAIR APPEARANCE 
ASSESSMENT: SUBJECT RATING (AFHA:SR)  
 
Instructions for item 1a: Please mark an “X” in the box (☐) that best describes the appearance 
of your left eyebrow hair right now. Please select the one response that best represents your 
answer. 
 Full eyebrow hair 
 Most eyebrow hair 
 Some eyebrow hair 
 A little eyebrow hair 
 No eyebrow hair 
 
Instructions for item 1b: Please mark an “X” in the box (☐) that best describes the appearance 
of your right eyebrow hair right now. Please select the one response that best represents your 
answer. 
 
 Full eyebrow hair 
 Most eyebrow hair 
 Some eyebrow hair 
 A little eyebrow hair 
 No eyebrow hair 
 
Instructions for item 2a: Please mark an “X” in the box (☐) that best describes the appearance 
of your left eyelashes right now. Please select the one response that best represents your answer. 
 
 Full eyelashes 
 Most eyelashes 
 Some eyelashes 
 A little eyelashes 
 No eyelashes 
 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 77 of 90 
CONFIDENTAL 
 
  
 
Instructions for item 2b: Please mark an “X” in the box (☐) that best describes the appearance 
of your right eyelashes right now. Please select the one response that best represents your 
answer. 
 
 Full eyelashes 
 Most eyelashes 
 Some eyelashes 
 A little eyelashes 
 No eyelashes 
 
Instructions for item 3: Please mark an “X” in the box (☐) that best describes the appearance 
of your beard hair right now. Beard hair can include hair on the chin, cheeks, neck, and above the 
upper lip. Please select the one response that best represents your answer. 
 
 Full beard hair 
 Most beard hair 
 Some beard hair 
 A little beard hair 
 No beard hair 
 N/A – Female  
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 78 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 5. SUBJECT GLOBAL IMPRESSION OF SEVERITY FOR 
PATCHY AA (SGIS-AAP) 
 
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-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 79 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 6. 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-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 80 of 90 
CONFIDENTAL 
 
  
 
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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Pr ot oc ol: A TI- 5 0 1- A U A T - 2 0 1 
 
Aclaris T hera pe utics , I nc. 
 
Date: 0 9 A P R 2 0 1 9 , V ersi o n 5 . 0                    
P a ge 8 1  of 9 0  
C O N FI D E N T A L  
 
  
 
A P P E N DI X  7.  S U B J E C T G L O B A L I M P R E S SI O N O F T R E A T M E N T 
S A TI S F A C TI O N  F O R A A P A T C H Y  ( S GI T S-A A P)  
 
Pl e as e m ar k a n “ X” i n t h e b ox ( ) t h at b est d escri b es h o w s atisfi e d y o u ar e wit h t h e tr e at m e nt 
f or y o ur p atc h y al o p eci a ar e at a. 
 
H o w s atisfi e d or diss atisfi e d ar e y o u wit h t h e tr e at m e nt y o u r ec ei v e d i n t his st u d y f or y o ur 
p atc h y al o p eci a ar e at a ?  
 
 E xtr e m el y s atisfi e d  
 M o d er at el y s atisfi e d  
 A littl e s atisfi e d  
 N eit h er s atisfi e d or diss atisfi e d  
 A littl e diss atisfi e d  
 M o d er at el y diss atisfi e d  
 E xtr e m el y diss atisfi e d  
 


Pr ot oc ol: A TI- 5 0 1- A U A T - 2 0 1 
 
Aclaris T hera pe utics , I nc. 
 
Date: 0 9 A P R 2 0 1 9 , V ersi o n 5 . 0                    
P a ge 8 2  of 9 0  
C O N FI D E N T A L  
 
  
 
A P P E N DI X  8.  S U B J E C T G L O B A L S A TI S F A C TI O N WI T H H AI R 
Q U A LI T Y ( S G S H Q -A A P ) 
I nstr ucti o ns: Pl e as e m ark a n “ X” i n t h e b ox ( ☐) t h at b est d escri b es y o ur s atisf acti o n wit h y o ur 
sc al p h air q u alit y (s uc h as its c ol or, t ext ur e, a n d t hic k n ess) ri g ht n o w. Pl e as e s el ect t h e o n e 
r es p o ns e t h at b est r e pr es e nts y o ur a ns w er. 
 
1. H o w s atisfi e d or diss atisfi e d ar e y o u wit h y o ur h air q u alit y i n t h e t ar g et p atc h ri g ht 
n o w ?  
 
 E xtr e m el y s atisfi e d  
 M o d er at el y s atisfi e d  
 A littl e s atisfi e d 
 N eit h er s atisfi e d or diss atisfi e d  
 A littl e diss atisfi e d  
 M o d er at el y diss atisfi e d  
 E xtr e m el y diss atisfi e d  
 
2. H o w s atisfi e d or diss atisfi e d ar e y o u wit h y o ur h air q u alit y i n t h e all tr e at e d p atc h y  
ar e as ri g ht n o w ? 
 
 E xtr e m el y s atisfi e d  
 M o d er at el y s atisfi e d  
 A littl e s atisfi e d  
 N eit h er s atisfi e d or diss atisfi e d  
 A littl e diss atisfi e d  
 M o d er at el y diss atisf i e d 
 E xtr e m el y diss atisfi e d  
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 83 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 9. 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 
             Not at all 
             Not relevant 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 84 of 90 
CONFIDENTAL 
 
  
 
 
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-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 85 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 10. ALOPECIA SCALP APPEARANCE ASSESSMENT FOR 
AT AND AU: SUBJECT RATING (ASAA-AT/AU:SR) 
 
Instructions: 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-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 86 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 11. SUBJECT GLOBAL IMPRESSION OF SEVERITY FOR 
AT/AU (SGIS-AT/AU) 
 
Please mark an “X” in the box (
) that best describes the severity of your alopecia totalis or 
alopecia universalis right now. 
 
Overall, how severe is your alopecia totalis or alopecia universalis right now? 
 
☐ Mild 
☐ Moderate 
☐ Severe 
☐ Very Severe 
☐ Extremely Severe 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 87 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 12. SUBJECT GLOBAL IMPRESSION OF TREATMENT 
SATISFACTION FOR AT/AU (SGITS-AT/AU) 
 
Please mark an “X” in the box (1) that best describes how satisfied you are with the treatment for 
your alopecia totalis or alopecia universalis. 
 
How satisfied or dissatisfied are you with the treatment you received in this study for your 
alopecia totalis or alopecia universalis? 
 
Extremely satisfied 
 
Moderately satisfied 
 
A little satisfied 
 
Neither satisfied or dissatisfied 
 
A little dissatisfied 
 
Moderately dissatisfied 
 
Extremely dissatisfied 
 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 88 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 13. SUBJECT GLOBAL SATISFACTION WITH HAIR 
QUALITY FOR AT/AU (SGSHQ-AT/AU) 
Instructions: Please mark an “X” in the box (☐) that best describes your satisfaction with your 
scalp hair quality (such as its color, texture, and thickness) right now. Please select the one 
response that best represents your answer. 
 
1. How satisfied or dissatisfied are you with your scalp hair quality right now? 
 
Extremely satisfied 
 
Moderately satisfied 
 
A little satisfied 
 
Neither satisfied or dissatisfied 
 
A little dissatisfied 
 
Moderately dissatisfied 
 
Extremely dissatisfied 
 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 89 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 14. 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 
 
 
 
 
  
 
 
  
 
 
  
 
  
 
 
 
 


Protocol: ATI-501-AUAT-201 
 
Aclaris Therapeutics, Inc. 
 
Date: 09APR2019, Version 5.0                    
Page 90 of 90 
CONFIDENTAL 
 
  
 
APPENDIX 15. STUDY MEDICATION INSTRUCTION SHEET 
General Instructions: 
1. Each month during the treatment phase of the study, the site staff will provide you with a 
one-month supply of study medication (with a few extra doses in case of spillage, loss or 
a missed appointment). 
2. Do not take the study medication on an empty stomach.  Food improves how much drug 
is absorbed and how much drug reaches your blood, which will give the drug the best 
chance of reaching your scalp.   
3. You will drink one bottle of study medication two times a day with a meal 
(approximately 8 to 12 hours between doses). 
4. Make sure the cap is tightly secured and gently shake the study medication before taking 
a dose. 
5. Swallow all the study medication in the bottle.   
6. Add water to the study medication bottle and drink the liquid, followed by a large glass 
of water.  
7. Do not change your dose without talking to the study doctor. 
8. Avoid excessive natural or artificial ultraviolet radiation (e.g., sunlight, tanning beds) and 
use sunscreen, if excessive sun exposure cannot be avoided. 
9. Remember to bring your compliance sheet, study medication bottles, both used and 
unused, to each study visit. 
 
 
Missed Doses 
If you miss a dose of this study medication, take the dose 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 bottle at room temperature, away from heat, moisture, 
and direct light. Do not refrigerate or freeze. Keep out of reach of children. 
 
 
 
 

SAP_001.pdf: 
Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
Study Title:  
A Randomized, Double-Blind, Placebo-Controlled Multicenter 
Study to Evaluate the Safety, Tolerability and Efficacy of ATI-
501 Oral Suspension Compared to Placebo in Adult Subjects 
with Alopecia Areata, Alopecia Universalis or Alopecia Totalis 
Phase: 
II 
 
 
Protocol No.: 
ATI-501-AUAT-201   
 
 
Protocol Date(s): 
Version 1.0, 26APR2018 
Version 2.0, 20JUL2018 
Version 3.0, 19SEP2018 
Version 4.0, 08NOV2018 
Version 5.0, 09APR2019 
 
 
Analysis Plan Version and 
Date: 
Version 1.0 Draft, 28MAY2019 
 
 
Prepared By: 
 
Andrew Garrison, 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-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 3 
28MAY2019 
 
TABLE OF CONTENTS 
GLOSSARY OF ABBREVIATIONS 
Abbreviation 
Term 
AA 
Alopecia Areata 
AAP 
Patchy Alopecia Areata 
AFHA 
Alopecia Facial Hair Appearance Assessment 
AT 
Alopecia Totalis 
AU 
Alopecia Universalis 
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 
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 
NSHA 
Non-Scalp Hair Loss Assessment 
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 
Scalp-ClinRO for AAP1 
Scalp-PRO 
Scalp-PRO for AAP2 
SGIC 
Subject Global Impression of Change 
SGIS 
Subject Global Impression of Severity 
SGITS 
Subject Global Impression of Treatment Satisfaction 
SGSHQ 
Subject Global Satisfaction with Hair Quality 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 4 
28MAY2019 
 
SR 
Subject Rating 
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-Clinician Rating (ASAA-CR) in the protocol. 
Subjects with Patchy AA complete Item 1 and Item 2 (target patch and whole scalp assessment). Subjects with Alopecia 
Totalis or Alopecia Universalis complete the assessment for the whole scalp only. 
2This assessment is named Alopecia Scalp Appearance Assessment-Subject Rating (ASAA-SR) in the protocol.  Subjects 
with Patchy AA complete Item 1 and Item 2 (target patch and whole scalp assessment). Subjects with Alopecia Totalis or 
Alopecia Universalis complete the assessment for the whole scalp only. 
 
 
 
 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 5 
28MAY2019 
 
1. 
INTRODUCTION 
This document describes the statistical methods and data presentations to be used in the summary 
and analysis of data from Protocol ATI-501-AUAT-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 evaluation of the psychometric properties of the newly 
developed patient-reported and clinician-reported outcome (PRO and ClinRO) questionnaires. 
Additionally, the generation of score interpretation estimates for the clinical outcome assessments 
to guide the definition of responders in pivotal trials is also not within the scope of this SAP. 
 
1.1. 
STUDY OVERVIEW 
ATI-501-AUAT-201 is a Phase 2, multicenter, randomized, double-blind study designed to 
evaluate the safety, tolerability and efficacy of ATI-501 Oral Suspension in subjects with alopecia 
areata (AA), alopecia universalis (AU), or alopecia totalis (AT). Subjects will be required to have a 
clinical diagnosis of stable AA, AU, or AT with at least 30% up to 100% total scalp hair loss for a 
duration of at least 6 months up to and including 12 years. 
 
 Treatment Assignment:   
A total of approximately 95 subjects will be randomized in a 1:1:1:1 ratio: 
• 
Placebo Oral Suspension, twice daily (BID) for 24 weeks (6 months) 
• 
ATI-501 Oral Suspension, 400 mg, BID for 24 weeks (6 months) 
• 
ATI-501 Oral Suspension, 600 mg, BID for 24 weeks (6 months) 
• 
ATI-501 Oral Suspension, 800 mg, BID for 24 weeks (6 months) 
 
During the screening period, subjects will be assessed for eligibility into the study. Subjects will 
receive ATI-501 Oral Suspension, 400 mg, 600 mg, or 800 mg or Placebo Oral Suspension twice-
daily for up to 24 weeks. Assessment of response to treatment will be performed at Week 4 (Visit 
4), Week 8 (Visit 5), Week 12 (Visit 6), Week 16 (Visit 7), Week 20 (Visit 8), Week 24 (Visit 9), 
and post-treatment (Visit 10). Safety and tolerability will be evaluated at each study visit by 
assessment of adverse events (AEs), clinical lab tests, vital signs, and at select visits, ECGs. The 
primary analysis will be conducted after all subjects complete Visit 9 or Visit 10.  
 
Subjects who complete Visit 9 (Week 24) will be eligible to enter a 28-week open-label study ATI-
502-AA-203.  Subjects who decline or are not eligible for ATI-502-AA-203 should be seen for the 
Visit 10 (Post-treatment) assessments.  
 


Aclaris Therapeutics, Inc. 
 
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201 
 
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 6 
 
 
 
28MAY2019 
 
1.2. 
SCHEDULE OF ASSESSMENTS 
 
Screening 
Baseline 
Treatment 
Post-Treatment 
 
Visit 1 
Visit 2 
Visit 
31 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
(ET) 
Visit 1019 
Week  
 
0 
2 
4 
8 
12 
16 
20 
24 
28 
Treatment Day 
-30 to 0 
1 
15 
29 
57 
85 
113 
141 
169 
197 
Treatment window (days) 
N/A 
N/A 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Informed consent2 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
Physical exam3 
X 
 
 
 
 
 
 
 
X 
 
Demographics & medical history 
X 
 
 
 
 
 
 
 
 
 
Alopecia Areata History 
X 
 
 
 
 
 
 
 
 
 
Vital signs4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Complete Blood Count (CBC), Chemistry, Virology, 
Serum Pregnancy, Urinalysis5 
X4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for PK (Select Sites Only)6 
 
X (Pre-
dose) 
 
X 
 
X 
 
 
X 
 
Urine pregnancy test7 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
 
X 
 
 
 
 
 
X 
 
Subject8 
Target Patch identification (Patchy AA Subjects Only) 
 
X 
 
 
 
 
 
 
 
 
Scalp-PRO 
Target Patch, Whole Scalp9 
 
X 
X 
 
 
X 
 
 
X 
X 
Alopecia Facial Hair Appearance Assessment (AFHA: SR) 
 
X 
X 
 
 
X 
 
 
X 
X 
Subject Global Impression of Severity (SGIS-AAP (patchy 
alopecia areata) or SGISAT/AU) 
 
X 
X 
 
 
X 
 
 
X 
X 
Alopecia Impact Assessment (AIA):  Subject Rating 
 
X 
X 
 
 
X 
 
 
X 
X 
Subject Global Impression of Change (SGIC) 
 
 
 
 
 
 
 
 
X 
 
Subject Global Impression Treatment Satisfaction 
(SGITSAAP or SGITSAT/AU)10 
 
 
 
 
 
X 
 
 
X 
X 
Subject Global Satisfaction with Hair Quality 
(SGSHQAAP or SGSHQAT/AU) 
 
X 
X 
 
 
X 
 
 
X 
X 
DLQI11 
 
 
 
 
 
 
 
X 
X 
 
 
X 
 
 
X 
X 


Aclaris Therapeutics, Inc. 
 
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201 
 
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 7 
 
 
 
28MAY2019 
 
 
Screening 
Baseline 
Treatment 
Post-Treatment 
 
Visit 1 
Visit 2 
Visit 
31 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
(ET) 
Visit 1019 
Week  
 
0 
2 
4 
8 
12 
16 
20 
24 
28 
Treatment Day 
-30 to 0 
1 
15 
29 
57 
85 
113 
141 
169 
197 
Treatment window (days) 
N/A 
N/A 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Investigator12 
Scalp-ClinRO 
Target Patch, Whole Scalp13 
 
X 
X 
 
 
X 
 
 
X 
X 
Alopecia Facial Hair Appearance Assessment (AFHA: CR) 
 
X 
X 
 
 
X 
 
 
X 
X 
Non-Scalp Hair Loss Assessment (NSHA) 
 
X 
X 
 
 
X 
 
 
X 
X 
Physician Global Impression of Severity (PhGIS-AAP or 
PhGIS-AT/AU) 
 
X 
X 
 
 
X 
 
 
X 
X 
Physician Global Impression of Change (PhGIC) 
 
 
 
 
 
 
 
 
X 
 
Hair Quality Assessment (Patchy AA Subjects Only) 
 
X 
 
 
 
X 
 
 
X 
X 
SALT Score (prior to ALODEX)14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ALODEX Score (after SALT)15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vellus and Indeterminate Hair Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Photography (complete scalp) 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Subject randomization 
 
X 
 
 
 
 
 
 
 
 
Subject instructions16 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Dispense study medication17 
 
X 
X18 
X 
X 
X 
X 
X 
 
 
Collect study medication and assess compliance17 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant therapies 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Abbreviations:  CR= Clinician Rating; ET= Early termination Visit; SR= Subject Rating 
1 Efficacy assessments completed at Visit 3 are to test the reliability of the clinician and patient reported outcome tools. 
2 A written, signed informed consent form (ICF) 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). 
3 A physical exam includes: general appearance, examination of head, eyes, ears, nose and throat, respiratory, cardiovascular, abdominal, neurological, musculoskeletal, 
extremities, lymphatic and skin assessment (other than AA). 
4 Vitals signs include: oral or ear temperature, blood pressure, heart rate, respiration rate (height and weight at Screening only). 
5 Clinical laboratory non-fasting sampling includes: CBC, Chemistry with lipids, Urinalysis.  Quantiferon Gold, Human Immunodeficiency Virus (HIV), Hepatitis B and C, 
TIBC, Serum Iron, Serum Ferritin, T3, free T4, TSH and Serum Pregnancy should be done at screening visit only.    
6 At  Select sites:  A single 4.5 mililiters (mL) sodium citrate vacutainer should be drawn at Visit 2 (predose) and Visits 4, 6, and 9, 12 hours (± 30 minutes) after the prior 
evening dose.  Subjects participating in the PK analysis should be called the day prior to Visit 4, 6, and 9 to remind them to take their evening dose approximately 11 hours 
prior to the visit time and to document the time of the evening dose. 


Aclaris Therapeutics, Inc. 
 
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201 
 
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 8 
 
 
 
28MAY2019 
 
7 Subjects who are women of child-bearing potential (WOCBP) should have a urine pregnancy test (UPT) performed early in the screening procedures (following informed 
consent) which shows negative results in order to avoid the continuation of what would then be unnecessary screening testing.  Subjects who are WOCBP must also have a 
negative serum pregnancy test result from Screening (Visit 1) to continue in the study, and a negative UPT at Baseline (Visit 2) prior to randomization.  UPTs in WOCBP 
must also be obtained at Visits 4, 5, 6, 7, 8, 9 and 10 and must be negative for the subject to continue in the study. 
8 The subject should perform assessments prior to the Investigator assessments.  The investigator may assist the subject in locating a Target Patch. 
9 Subjects with 30% to 95% scalp hair loss will identify the most bothersome patchy area at Baseline (Visit 2). A score of “no hair” or “a little hair” in the target patch is 
required. For subjects with AU or AT, the target patch identification at Baseline (Visit 2) will be recorded as “Not Applicable” in the source document and eCRF. 
10 The study staff should remind the subject that this question is in relation to the satisfaction with the result of the hair regrowth. 
11 The study staff should remind the subject that the questions are in relation to hair loss and not skin. 
12 Investigator assessments should be performed after the Subject Assessments. 
13 In subjects with patchy AA, the assessment of hair quality will be performed at the edge of the target patch.  For subjects with AU/AT, the assessment of hair quality will be 
recorded as Not Applicable in the source document and eCRF. At Baseline (Visit 2), the assessment should be determined prior to the first dose of study medication. 
14 SALT score must be determined prior to ALODEX using device provided. 
15ALODEX score determined after SALT score using device provided. 
16 The study staff must instruct the subject to dose study medication according to the instructions in Appendix 15. 
17Staff should review the usage based on the number of used and unused bottles and counsel the subject as necessary. 
18At Visit 3, the subject’s Month 1 drug supply carton should be reviewed by site staff as part of compliance activities and then released back to the subject for continued use. 
19 Subjects who complete study visits through Visit 9 will have the option to roll over into an open-label study ATI-502-AA-203.  Subjects who withdraw consent or meet 
study medication discontinuation criteria (Section 3.4.1.2) on study ATI-501-AUAT-201 will not be eligible for roll-over to study ATI-502-AA-203.  Subjects who complete 
the assessments for Visit 9 and then meet study ATI-502-AA-203 entry criteria and provide written consent will skip post-treatment Visit 10.   Subjects who are not eligible 
for ATI-502-AA-203 or who decline to participate should return for the final Visit 10 assessments. 
 
   
 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 9 
28MAY2019 
 
2. 
OBJECTIVES 
Primary Objective: 
 
The primary objective is to assess the safety, tolerability and efficacy of ATI-501 Oral Suspension, 
400 mg, 600 mg, or 800 mg compared to Placebo Oral Suspension in subjects with AA, AU, or 
AT. 
 
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. This objective is not within the scope of the SAP.  
• 
To generate score interpretation estimates for the clinical outcome assessments to guide the 
definition of responders in pivotal trials. This objective is not within the scope of the SAP.  
• 
To assess the concentration level of ATI-502 in the blood at trough. 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 10 
28MAY2019 
 
3. 
EFFICACY AND SAFETY ASSESSMENTS 
Efficacy assessments include the following scores and/or scales (Note: Target Patch and Entire 
Scalp assessments are performed for AAP subjects. Only Entire Scalp assessments are performed 
for AT/AU subjects): 
 
• 
Severity Alopecia Tool (SALT) Score 
• 
Alopecia Density and Extent Score (ALODEX) 
• 
Item 1 and Item 2 Scalp-ClinRO for AAP (Scalp-AAP-ClinRO), referred to as Alopecia Scalp 
Appearance Assessment (ASAA-AAP:CR) in the protocol  
• 
Scalp-ClinRO for AT/AU (Scalp-AT/AU-ClinRO), referred to as Alopecia Scalp Appearance 
Assessment (ASAA-AT/AU:CR) in the protocol  
• 
Item 1 and Item 2 Scalp-PRO for AAP (Scalp-AAP-PRO), referred to as Alopecia Scalp 
Appearance Assessment (ASAA-AAP:SR) in the protocol   
• 
Scalp-PRO for AT/AU (Scalp-AT/AU-PRO), referred to as Alopecia Scalp Appearance 
Assessment (ASAA-AT/AU:SR) in the protocol  
• 
Physician Global Impression of Severity (PhGIS-AAP or PhGIS-AT/AU) 
• 
Alopecia Facial Hair Appearance Assessment (AFHA-PRO and AFHA-ClinRO) 
• 
Subject Global Impression of Severity (SGIS-AAP or SGIS-AT/AU)  
• 
Alopecia Impact Assessment (AIA) – Subject Rating 
• 
Subject Global Impression of Treatment Satisfaction (SGITS-AAP or SGITS-AT/AU) 
• 
Subject Global Satisfaction with Hair Quality (SGSHQ-AAP or SGSHG-AT/AU) 
• 
Dermatology Life Quality Index (DLQI) total score 
• 
Physician Global Impression of Change (PhGIC) 
• 
Subject Global Impression of Change (SGIC) 
• 
Hair Quality Assessment (Hair Pull Test, AAP subjects only) 
• 
Vellus and Indeterminate scalp hair 
• 
Non-scalp hair assessments (body and nasal hair) (NSHA) 
 
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 (ECGs) 
 
 
 
 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 11 
28MAY2019 
 
4. 
GENERAL STATISTICAL CONSIDERATIONS 
4.1. 
SAMPLE SIZE AND POWER 
The planned sample size is 95 enrolled subjects with approximately 45 subjects enrolled with AT or 
AU. It is assumed that the proportion of subjects who achieve at least a 50% reduction in hair loss 
(SALT50) for the pooled 600mg and 800mg treatment groups will be at least 32%, and the SALT50 
for the pooled placebo and 400mg treatment groups will be at most 6%. Assuming a 10% dropout 
rate, this results in >80% power for the SALT50 analysis. Because the primary efficacy analysis of 
mean percent change in hair loss using SALT scores is expected to be more sensitive than the SALT50 
responder analysis, the power for the primary analysis is also expected to be no less than 84%.     
 
4.2. 
RANDOMIZATION AND BLINDING 
 
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 treatment period, subjects will be assigned to 1 of the 4 treatment groups in a random manner 
and at a 1:1:1:1 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.    
  
This study uses a double-blind design.  The study medications are indistinguishable in appearance, 
as packaged and labeled.  
 
4.3. 
HANDLING OF DATA 
4.3.1. 
Strata and Covariates 
No stratified analyses are planned. 
4.3.2. 
Examination of Subject Subsets 
The baseline SALT score group (< 50, ≥50) will be used for subset analyses.  Additionally, 
duration of current episode (< 4 years, ≥ 4 years) will be used for subset analyses. The details of the 
subset analyses are given in the statistical analysis section.   
4.3.3. 
Multiple Testing and Comparisons  
There are no planned adjustments for multiple comparisons. 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 12 
28MAY2019 
 
4.3.4. 
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. 
 
4.3.5. 
Imputation of Incomplete Dates 
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. 
For purposes of imputation, all events with an incomplete end date are assumed to have ended on 
or before the day the form was completed. 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). 
 
4.3.6. 
Definitions and Terminology  
 
Day 1 
Day 1 is defined as the date of the initial study medication dose as reported on the study medication 
usage page of the CRF. 
 
Study Day  
Study Day is defined relative to Day 1.  Thus, the study day of an event is calculated as: 
Study Day = ((event date – date of Day 1) + 1) for dates on or after Day 1  
Study Day = (event date – date of Day 1) for dates prior to Day 1 
Study Day  
Study day will be relative to the defined Day 1.   
 
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 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 13 
28MAY2019 
 
 
Last Dose of Study Medication  
Last Dose of Study Medication is defined as the last date that the subject took oral medication in 
the treatment period as determined by last date of recorded on the study medication usage page of 
the CRF. 
Study Medication Exposure (days)  
Study drug exposure is defined as the (date of last 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 doses per day field on the study medication page of eCRF.  
Missed Dose 
A missed dose is defined as a single day where ‘None’ was checked for the number of doses per 
day field on the study medication page of eCRF.  
Study medication compliance (%) based on number of doses 
The compliance with the dosing regimen will be calculated based on the subject-specific dose 
regimen as, [(study medication exposure days - number of days with less than the subject-specific 
expected number of doses) / (study medication exposure days)] x 100.  
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 the CRF.   
Duration of current episode of alopecia 
Date of Informed Consent minus the onset date of current episode of Alopecia as reported on the 
History of Alopecia page of the CRF.   
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. 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 14 
28MAY2019 
 
 
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 
An AE is the development of an undesirable medical condition or the deterioration of a preexisting 
medical condition following or during exposure to a pharmaceutical product, whether or not 
considered casually related to the product. 
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.  Hair growth in unexpected areas, such as 
facial hair in women, should be reported as an adverse event 
 
Treatment-Emergent Adverse Event (TEAE) 
Any recorded AE that occurs on or after the initiation of study medication and within 30 days after 
the date of Visit 9 or 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.   
 
4.3.7. 
Presentations by Study Visit 
Results from efficacy assessments and safety will be summarized by study visit and treatment 
group. 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 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.  


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 15 
28MAY2019 
 
Table 1: Visit Windows 
Nominal Visit 
Target Study Day 
Analysis Visit 
Study Day Range 
Screening 
-30 to -1 
Baseline 
≤1 
Day 1 
1 
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 – 182] 
 
For the post-treatment visit 10, the analyses will be based on the nominal study visit as reported on 
the CRF.  
 
4.4. 
TIMING OF ANALYSES 
When all subjects have completed study AA-501-AUAT-201 or terminated early from the blinded 
treatment period and the database has been locked and forwarded for analysis, the study will be 
unblinded and the safety and efficacy analysis will be performed according to this SAP. 
No interim analysis is planned for this study 
5. 
ANALYSIS POPULATIONS 
The populations for analysis will include the intent-to-treat population (ITT), the safety population 
(SAF), the per protocol (PP) population, and the pharmacokinetics (PK) population. 
5.1. 
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. 
5.2. 
SAFETY POPULATION  
 
The Safety population is defined as all randomized subjects who received at least one dose 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. 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 16 
28MAY2019 
 
5.3. 
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 administer at least 75% of study medication 
4. Did not complete Week 24 (Visit 9). 
This population will be used for supportive analyses of key efficacy endpoints.  
5.4. 
PHARMACOKINETICS (PK) POPULATION 
The Pharmacokinetics (PK) population is defined as all subjects who receive at least one dose of 
study medication and have at least one measurable ATI-502 concentration value. Subjects in this 
population will be analyzed according to the treatment which they receive. All PK analyses will be 
based on this population.   
6. 
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.  
The term ‘treatment group’ refers to ATI-501 active groups and matching Placebo Oral Suspension 
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 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 17 
28MAY2019 
 
endpoints, the ATI-501 treatment groups will be tested versus Placebo Oral Suspension 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 prior to issuance of the draft statistical 
report. All documents will be reviewed by the lead statistician to ensure accuracy and consistency. 
6.1. 
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. 
Baseline characteristics, including diagnosis type (Areata, Universalis, Totalis), ophiasis pattern of 
hair loss, duration of alopecia, duration of current episode of alopecia (continuous and 
dichotomized (< 4 years, ≥ 4 years)), baseline hair pull test results (dislodged hairs and broken 
hairs), baseline vellus and indeterminate hair assessment, baseline SALT score group (<50%, 
>50%) and baseline Scalp-ClinRO (target patch and entire scalp) and Scalp-PRO (target patch and 
entire scalp) 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 
(NCS) and abnormal clinically significant (CS).  
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.   


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 18 
28MAY2019 
 
6.2. 
EFFICACY ANALYSIS 
 
6.2.1. 
Primary Efficacy Endpoint 
The primary efficacy variable will be the mean percent change from baseline in the SALT score at 
Week 24 (Visit 9). 
 
6.2.2. 
Primary Efficacy Analysis 
Descriptive statistics for the SALT score, change, and percent change from baseline will be 
presented by 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, and treatment by study visit 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.  
 
6.2.3. 
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 PP 
population and the ITT population. 
 
 
6.2.4. 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints include:  
• 
Percent change from baseline in the ALODEX score at Week 24 (Visit 9), also described as 
mean percent regrowth, 
• 
Mean change from baseline in SALT score at Week 24 (Visit 9) 
• 
Mean change from baseline in ALODEX score at Week 24 (Visit 9)  
• 
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-AAP-PRO and Scalp-AT/AU-PRO at Week 24 (Visit 9)  
• 
Change from baseline in the Scalp-AAP-ClinRO and Scalp-AT/AU-PRO at Week 24 (Visit 9) 
• 
Change from baseline in the PhGIS-AAP and PhGIS-AT/AU at Week 24 (Visit 9) 
• 
Change from baseline in AFHA-ClinRO at Week 24 
• 
Change from baseline in AFHA-PRO at Week 24 
• 
Change from baseline in the SGIS-AAP and SGIS-AT/AU at Week 24 (Visit 9) 
• 
Change from baseline in SGSHQ-AAP and SGSHQ-AT/AU at Week 24 
• 
Change from baseline in the subject reported AIA at Week 24 (Visit 9) 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 19 
28MAY2019 
 
• 
SGITS-AAP and SGITS-AT/AU at Week 24 (Visit 9) 
• 
Change in DLQI total score between Baseline and Week 24 (Visit 9) 
• 
PhGIC at Week 24 (Visit 9) 
• 
SGIC at Week 24 (Visit 9) 
 
6.2.5. 
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:  
• 
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 
(patchy AA subjects only) 
• 
Proportion of subjects with ≥ 2-point improvement in Scalp-PRO for the Target Area (patchy 
AA subjects only) 
• 
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 a factor for treatment. The p-
value for the overall global test that β= 0 for this factor will be presented. The adjusted odds ratios 
(95% CI) for being a responder (active/placebo oral suspension) will be presented along with the 
associated p-value.  
The questionnaires Scalp-PRO, Scalp-ClinRO, PhGIS, AFHA, and SGIS are collected on a 1-5 
scale. The SGSHQ questionnaire is collected on a 1-7 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 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 placebo oral suspension.   


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 20 
28MAY2019 
 
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 placebo oral suspension. 
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.  
6.2.6. 
Other Efficacy 
Results from the Hair Quality Assessment (hair pull test) will be summarized. The summary will 
show the shift relative to baseline in the categories of dislodged hairs and broken hairs at Week 24 
(Visit 9). 
Results from the Vellus and Indeterminate Hair Assessment will be summarized. The summary 
will show the shift relative to baseline at Week 24 (Visit 9) in the categories of vellus hair present 
and indeterminate hair present. 
NSHA results will also be summarized. The summary will show the shift relative to baseline at 
Week 24 (Visit 9) in the Body Hair Loss categories of no body hair loss, some hair loss, and total 
body hair loss and in the Nasal Hair Loss categories of no nasal hair loss to some to total hair loss. 
6.2.7. 
Subset Analyses 
• 
Subgroups of Baseline SALT score group (< 50, ≥50) 
• 
Subgroups of duration of current alopecia episode (<4 years, ≥4 years) 
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 
each subgroup. 
6.2.8. 
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.  
6.3. 
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). 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 21 
28MAY2019 
 
6.3.1. 
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 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. 
6.3.2. 
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, 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 22 
28MAY2019 
 
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. 
6.3.3. 
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 (CS and NCS) 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 milliseconds (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 
6.4. 
PHARMAKOKINETICS 
6.4.1. 
Pharmacokinetic Analyses 
The concentration of ATI-502 in the blood will be summarized for the treatment period at pre-
dose (Visit 2) and approximately 12-hr post dosing at Visits 4, 6 and 9. 
7. 
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. 
 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 23 
28MAY2019 
 
8. 
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.  The number of missing observations, if any, will be noted. 
• 
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.  
The number of missing observations, if any, will be noted. 
• 
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.   


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 24 
28MAY2019 
 
• 
Standard deviations will be reported to two decimal places beyond the number of decimal 
places the original parameter is presented. 
• 
Means will be reported to one decimal place beyond the number of significant digits as the 
parameter.  
• 
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). 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 25 
28MAY2019 
 
9. 
PROPOSED TABLES, LISTINGS, AND FIGURES 
 
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 Alopecia, ITT Population 
8. Table 14.1.7 Medical History, ITT Population 
9. Table 14.1.8 Physical Examination at Screening, ITT Population 
10. Table 14.1.9.1 Prior Medications Safety Population 
11. Table 14.1.9.2 Concomitant Medications Safety Population 
12. Table 14.1.10 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 Change from Baseline in SALT Score (LOCF), ITT Population 
ALODEX 
20. Table 14.2.2.1 Summary of ALODEX Score, Change from Baseline, and Percent Change 
from Baseline by Visit (LOCF), ITT Population 
21. Table 14.2.2.2 Analysis of Percent Change from Baseline in ALODEX (LOCF), ITT 
Population 
22. Table 14.2.2.3 Analysis of Change from Baseline in ALODEX Score (LOCF), ITT 
Population 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 26 
28MAY2019 
 
Responder Endpoints 
23. Table 14.2.3.1 Proportion of Subjects Achieving ≥50% Hair Regrowth Based on SALT 
Score, ITT Population 
24. Table 14.2.3.2 Proportion of Subjects Achieving ≥50% Hair Regrowth Based on ALODEX 
Score, ITT Population 
25. Table 14.2.3.3 Proportion of Subjects Achieving an Absolute SALT Score ≤ 10, ITT 
Population 
26. Table 14.2.3.4 Proportion of Subjects with ≥ 2 Point Improvement in Scalp-ClinRO for 
Target Patch, AAP Subjects, ITT Population 
27. Table 14.2.3.5 Proportion of Subjects with ≥ 1 Point Improvement in Scalp-ClinRO for 
Entire Scalp, ITT Population 
28. Table 14.2.3.6 Proportion of Subjects with ≥ 2 Point Improvement in Scalp-PRO for 
Target Patch, AAP Subjects, ITT Population 
29. 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 
30. Table 14.2.4.1 Analysis of Change from Baseline in Scalp-ClinRO for Target Patch, AAP 
Subjects, ITT Population 
31. Table 14.2.4.2 Analysis of Change from Baseline in Scalp-ClinRO for Entire Scalp, ITT 
Population 
32. Table 14.2.4.3 Analysis of Change from Baseline in Scalp-PRO for Target Patch, AAP 
Subjects, ITT Population 
33. Table 14.2.4.4 Analysis of Change from Baseline in Scalp-PRO for Entire Scalp, ITT 
Population 
PhGIS and SGIS 
34. Table 14.2.5.1 Analysis of Change from Baseline in Physician Global Impression of 
Severity (PhGIS), AAP Subjects, ITT Population 
35. Table 14.2.5.2 Analysis of Change from Baseline in Physician Global Impression of 
Severity (PhGIS), AU/AT Subjects, ITT Population 
36. Table 14.2.5.3 Analysis of Change from Baseline in Subject Global Impression of Severity 
(SGIS), AAP Subjects, ITT Population 
37. Table 14.2.5.4 Analysis of Change from Baseline in Subject Global Impression of Severity 
(SGIS), AU/AT Subjects, ITT Population 
 
 
 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 27 
28MAY2019 
 
AFHA 
38. Table 14.2.6.1.1 Analysis of Change from Baseline in Alopecia Facial Hair Appearance 
Assessment (AFHA-ClinRO), Left Eyebrow, ITT Population 
39. Table 14.2.6.1.2 Analysis of Change from Baseline in Alopecia Facial Hair Appearance 
Assessment (AFHA-ClinRO), Right Eyebrow, ITT Population 
40. Table 14.2.6.1.3 Analysis of Change from Baseline in Alopecia Facial Hair Appearance 
Assessment (AFHA-ClinRO), Left Eyelash, ITT Population 
41. Table 14.2.6.1.4 Analysis of Change from Baseline in Alopecia Facial Hair Appearance 
Assessment (AFHA-ClinRO), Right Eyelash, ITT Population 
42. Table 14.2.6.1.5 Analysis of Change from Baseline in Alopecia Facial Hair Appearance 
Assessment (AFHA-ClinRO), Beard, Male Subjects, ITT Population 
43. Table 14.2.6.2.1 Analysis of Change from Baseline in Alopecia Facial Hair Appearance 
Assessment (AFHA-PRO), Left Eyebrow, ITT Population 
44. Table 14.2.6.2.2 Analysis of Change from Baseline in Alopecia Facial Hair Appearance 
Assessment (AFHA- PRO), Right Eyebrow, ITT Population 
45. Table 14.2.6.2.3 Analysis of Change from Baseline in Alopecia Facial Hair Appearance 
Assessment (AFHA- PRO), Left Eyelash, ITT Population 
46. Table 14.2.6.2.4 Analysis of Change from Baseline in Alopecia Facial Hair Appearance 
Assessment (AFHA- PRO), Right Eyelash, ITT Population 
47. Table 14.2.6.2.5 Analysis of Change from Baseline in Alopecia Facial Hair Appearance 
Assessment (AFHA- PRO), Beard, Male Subjects, ITT Population 
 
SGSHQ 
48. Table 14.2.7.1 Analysis of Change from Baseline in Subject Global Satisfaction with Hair 
Quality (SGSHQ) for Target Patch, AAP Subjects, ITT Population 
49. Table 14.2.7.2 Analysis of Change from Baseline in Subject Global Satisfaction with Hair 
Quality For Entire Scalp (SGSHQ), ITT Population 
PhGIC and SGIC 
50. Table 14.2.8.1   Physician Global Impression of Change (PhGIC) at Week 24, ITT 
Population 
51. Table 14.2.8.2 Subject Global Impression of Change (SGIC) at Week 24, ITT Population 
Other Efficacy 
52. Table 14.2.9.1   Subject Global Impression of Treatment Satisfaction (SGITS) over Time, 
AAP Subjects, ITT Population 
53. Table 14.2.9.2   Subject Global Impression of Treatment Satisfaction (SGITS) over Time, 
AU/AT Subjects, ITT Population 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 28 
28MAY2019 
 
54. Table 14.2.10.1 Summary of DLQI Score and Change from Baseline by Visit, ITT 
Population 
55. Table 14.2.10.2 Analysis of Change from Baseline in DLQI Total Score over Time, ITT 
Population 
56. Table 14.2.11.1 AIA–PRO, Total Score, ITT Population  
57. Table 14.2.11.2 AIA–PRO, Cover Hair Loss, ITT population 
 
58. Table 14.2.11.3 AIA–PRO, Worried about Appearance, ITT population 
59. Table 14.2.11.4 AIA–PRO, Sad Due to Hair Loss, ITT population 
60. Table 14.2.11.5 AIA–PRO, Confidence, ITT population 
61. Table 14.2.11.6 AIA–PRO, Self-Conscious, ITT population 
62. Table 14.2.11.7 AIA–PRO, Embarrassed, ITT population 
63. Table 14.2.11.8 AIA–PRO, Unattractive, ITT population 
64. Table 14.2.11.9 AIA–PRO, Limit Social Activity, ITT population 
65. Table 14.2.11.10 AIA–PRO, Limit Physical Activity, ITT population 
66. Table 14.2.11.11 AIA–PRO, Unwanted Attention, ITT population 
67. Table 14.2.11.12 AIA–PRO, Sweat in Eyes, ITT population 
 
68. Table 14.2.11.13 AIA–PRO, Debris in Eyes, ITT population 
 
69. Table 14.2.11.14 AIA–PRO, Debris in Nose, ITT population 
70. Table 14.2.12 Shift from Baseline to Week 24 in Hair Pull Test Results - Dislodged Hairs 
and Broken Hairs, AAP Subjects, ITT Population  
71. Table 14.2.13 Shift from Baseline to Week 24 in Vellus and Indeterminate Hair 
Assessment Results, ITT population 
72. Table 14.2.14, Shift from Baseline to Week 24 in Non-Scalp Hair Loss (NSHA) 
Assessment Results – Body Hair Loss and Nasal Hair Loss, ITT population 
Subgroup Analyses 
73. Table 14.2.15.1 Analysis of Percent Change from Baseline in SALT Score (LOCF), ITT 
Population, Baseline SALT < 50 
74. Table 14.2.15.2 Analysis of Percent Change from Baseline in SALT Score (LOCF), ITT 
Population, Baseline SALT ≥ 50 
75. Table 14.2.15.3 Analysis of Percent Change from Baseline in SALT Score (LOCF), ITT 
Population, Duration of Current Alopecia Episode < 4 Years 
76. Table 14.2.15.4 Analysis of Percent Change from Baseline in SALT Score (LOCF), ITT 
Population, Duration of Current Alopecia Episode ≥ 4 Years 
77. Table 14.2.16.1 Analysis of Percent Change from Baseline in ALODEX Score (LOCF), 
ITT Population, Baseline SALT < 50 
78. Table 14.2.16.2 Analysis of Percent Change from Baseline in ALODEX Score (LOCF), 
ITT Population, Baseline SALT ≥ 50 
79. Table 14.2.16.3 Analysis of Percent Change from Baseline in ALODEX Score (LOCF), 
ITT Population, Duration of Current Alopecia Episode < 4 Years 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 29 
28MAY2019 
 
80. Table 14.2.16.4 Analysis of Percent Change from Baseline in ALODEX Score (LOCF), 
ITT Population, Duration of Current Alopecia Episode ≥ 4 Years 
81. Table 14.2.17.1 Proportion of Subjects Achieving ≥50% Hair Regrowth Based on SALT 
Score, ITT Population, Baseline SALT < 50 
82. Table 14.2.17.2 Proportion of Subjects Achieving ≥50% Hair Regrowth Based on SALT 
Score, ITT Population, Baseline SALT ≥ 50 
83. Table 14.2.17.3 Proportion of Subjects Achieving ≥50% Hair Regrowth Based on SALT 
Score, ITT Population, Duration of Current Alopecia Episode < 4 Years 
84. Table 14.2.17.4 Proportion of Subjects Achieving ≥50% Hair Regrowth Based on SALT 
Score, ITT Population, Duration of Current Alopecia Episode ≥ 4 Years 
85. Table 14.2.18.1 Proportion of Subjects Achieving ≥50% Hair Regrowth Based on 
ALODEX Score, ITT Population, Baseline SALT < 50 
86. Table 14.2.18.2 Proportion of Subjects Achieving ≥50% Hair Regrowth Based on 
ALODEX Score, ITT Population, Baseline SALT ≥ 50 
87. Table 14.2.18.3 Proportion of Subjects Achieving ≥50% Hair Regrowth Based on 
ALODEX Score, ITT Population, Duration of Current Alopecia Episode < 4 Years 
88. Table 14.2.18.4 Proportion of Subjects Achieving ≥50% Hair Regrowth Based on 
ALODEX Score, ITT Population, Duration of Current Alopecia Episode ≥ 4 Years 
89. Table 14.2.19.1 Proportion of Subjects Achieving an Absolute SALT Score ≤ 10, ITT 
Population, Baseline SALT < 50 
90. Table 14.2.19.2 Proportion of Subjects Achieving an Absolute SALT Score ≤ 10, ITT 
Population, Baseline SALT ≥ 50 
91. Table 14.2.19.3 Proportion of Subjects Achieving an Absolute SALT Score ≤ 10, ITT 
Population, Duration of Current Alopecia Episode < 4 Years 
92. Table 14.2.19.4 Proportion of Subjects Achieving an Absolute SALT Score ≤ 10, ITT 
Population, Duration of Current Alopecia Episode ≥ 4 Years 
93. Table 14.2.20.1 Proportion of Subjects with ≥ 2 Point Improvement in Scalp-ClinRO for 
Target Patch, AAP Subjects, ITT Population, Baseline SALT < 50 
94. Table 14.2.20.2 Proportion of Subjects with ≥ 2 Point Improvement in Scalp-ClinRO for 
Target Patch, AAP Subjects, ITT Population, Baseline SALT ≥ 50 
95. Table 14.2.20.3 Proportion of Subjects with ≥ 2 Point Improvement in Scalp-ClinRO for 
Target Patch, AAP Subjects, ITT Population, Duration of Current Alopecia Episode < 4 
Years 
96. Table 14.2.20.4 Proportion of Subjects with ≥ 2 Point Improvement in Scalp-ClinRO for 
Target Patch, AAP Subjects, ITT Population, Duration of Current Alopecia Episode ≥ 4 
Years 
97. Table 14.2.21.1 Proportion of Subjects with ≥ 1 Point Improvement in Scalp-ClinRO for 
Entire Scalp, ITT Population, Baseline SALT < 50 
98. Table 14.2.21.2 Proportion of Subjects with ≥ 1 Point Improvement in Scalp-ClinRO for 
Entire Scalp, ITT Population, Baseline SALT ≥ 50 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 30 
28MAY2019 
 
99. Table 14.2.21.3 Proportion of Subjects with ≥ 1 Point Improvement in Scalp-ClinRO for 
Entire Scalp, ITT Population, Duration of Current Alopecia Episode < 4 Years 
100. 
Table 14.2.21.4 Proportion of Subjects with ≥ 1 Point Improvement in Scalp-
ClinRO for Entire Scalp, ITT Population, Duration of Current Alopecia Episode ≥ 4 Years 
101. 
Table 14.2.22.1 Proportion of Subjects with ≥ 2 Point Improvement in Scalp-PRO 
for Target Patch, AAP Subjects, ITT Population, Baseline SALT < 50 
102. 
Table 14.2.22.2 Proportion of Subjects with ≥ 2 Point Improvement in Scalp-PRO 
for Target Patch, AAP Subjects, ITT Population, Baseline SALT ≥ 50 
103. 
Table 14.2.22.3 Proportion of Subjects with ≥ 2 Point Improvement in Scalp-PRO 
for Target Patch, AAP Subjects, ITT Population, Duration of Current Alopecia Episode < 4 
Years 
104. 
Table 14.2.22.4 Proportion of Subjects with ≥ 2 Point Improvement in Scalp-PRO 
for Target Patch, AAP Subjects, ITT Population, Duration of Current Alopecia Episode ≥ 4 
Years 
105. 
Table 14.2.23.1 Proportion of Subjects with ≥ 1 Point Improvement in Scalp-PRO 
for Entire Scalp, ITT Population, Baseline SALT < 50 
106. 
Table 14.2.23.2 Proportion of Subjects with ≥ 1 Point Improvement in Scalp-PRO 
for Entire Scalp, ITT Population, Baseline SALT ≥ 50 
107. 
Table 14.2.23.3 Proportion of Subjects with ≥ 1 Point Improvement in Scalp-PRO 
for Entire Scalp, ITT Population, Duration of Current Alopecia Episode < 4 Years 
108. 
Table 14.2.23.4 Proportion of Subjects with ≥ 1 Point Improvement in Scalp-PRO 
for Entire Scalp, ITT Population, Duration of Current Alopecia Episode ≥ 4 Years 
Figures 
109. 
Figure 14.2.1.1.1 LS Mean Percent Change from Baseline (95% CI) in SALT 
Score Over Time by Treatment Group, ITT Population 
110. 
Figure 14.2.2.1.1 LS Mean Percent Change from Baseline (95% CI) in ALODEX 
Score Over Time by Treatment Group, ITT Population 
111. 
Figure 14.2.3.1.1 Proportion of Subjects Achieving a ≥ 50% Hair Regrowth 
Compared with Baseline using SALT Score by Treatment Group, ITT Population 
112. 
Figure 14.2.3.2.1 Proportion of Subjects Achieving a ≥ 50% Hair Regrowth 
Compared with Baseline using ALODEX Score by Treatment Group, ITT Population 
Section 14.3 Safety 
113. 
Table 14.3.1.1 Overall Summary of Adverse Events, Safety Population 
114. 
Table 14.3.1.2 Treatment-Emergent Adverse Events by System Organ 
Classification, Preferred Term, and Greatest Severity, Safety Population 
115. 
Table 14.3.1.3 Treatment-Emergent Adverse Events by System Organ 
Classification and Preferred Term, Safety Population 
116. 
Table 14.3.1.4 Treatment-Emergent Serious Adverse Events by SOC and PT, 
Safety Population 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 31 
28MAY2019 
 
117. 
Table 14.3.1.5 Treatment-Emergent Adverse Events Related to Study Drug by 
SOC and PT, Safety Population 
118. 
Table 14.3.1.6 Treatment-Emergent Adverse Events Leading to Discontinuation of 
Study Drug by SOC and PT, Safety Population 
119. 
Table 14.3.1.7 Study Drug Related Treatment-Emergent Adverse Events Leading 
to Discontinuation of Study Drug by SOC and PT, Safety Population 
120. 
Table 14.3.4.1.1 Summary of Hematology Results and Change from Baseline by 
Visit, Safety Population 
121. 
Table 14.3.4.1.2 Summary of Treatment-Emergent Abnormal Hematology Results, 
Safety Population 
122. 
Table 14.3.4.2.1 Summary of Serum Chemistry Results and Change from Baseline 
by Visit, Safety Population 
123. 
Table 14.3.4.2.2 Summary of Treatment-Emergent Abnormal Serum Chemistry 
Results, Safety Population 
124. 
Table 14.3.4.3.1 Summary of Urinalysis Results and Change from Baseline by 
Visit, Safety Population 
125. 
Table 14.3.4.3.2 Summary of Treatment-Emergent Abnormal Urinalysis Results, 
Safety Population 
126. 
Table 14.3.5.1.1 Summary of ECG Results and Change from Baseline by Visit, 
Safety Population 
127. 
Table 14.3.5.1.2 Proportion of Subjects with Abnormal ECG Interpretations, 
Safety Population 
128. 
Table 14.3.5.1.3 Proportion of Subjects with Noteworthy QT and QTcF Values 
and Changes from Baseline by Visit 
129. 
Table 14.3.5.2.1 Summary of Vital Signs and Change from Baseline, Safety 
Population 
 
Section 14.4 Pharmacokinetics 
130. 
Table 14.4.1 Summary ATI-502 Concentrations and Change from Baseline, PK 
Population 
 
 
 
 
 
 
 
 
 
 
 
 


Aclaris Therapeutics, Inc.  
Statistical Analysis Plan 
Protocol: ATI-501-AUAT-201  
Version Date: 28MAY2019 
 
 
 
 
CONFIDENTIAL 
Page 32 
28MAY2019 
 
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. AFHA 
14. SGSHQ 
15. SGITS 
16. DQLI Questions and Total Score 
17. AIA-PRO Scale Items and Total Score 
18. PhGIC and SGIC 
19. Hair Quality Assessments – Hair Pull Test 
20. Vellus and Indeterminate Hair Assessment (AAP Subjects) 
21. NSHA 
22. Adverse Events 
23. Serious Adverse Events 
24. Adverse Events Leading to Discontinuation 
25. Laboratory Tests – Panel 
26. Lab Abnormalities 
27. Vital Signs 
28. Physical Examination 
29. ECG 
30. ATI-502 Concentrations